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1.  Methods of time sampling: A reappraisal of momentary time sampling and partial interval recording 
We compared the accuracy of momentary time sampling (MTS) and partial interval recording (PIR) in estimating both absolute behavioral levels and relative change. A computer randomly generated runs of pseudobehavior varying in duration and rate and simulated MTS and PIR of each run. Results indicated that when estimating absolute behavioral levels, duration rather than rate should be used as the dependent measure, and MTS is more accurate than PIR. In contrast, PIR is the more sensitive method for detecting relative changes in behavioral levels, although, at high rates, PIR tends to underestimate the degree of change.
PMCID: PMC1308042  PMID: 16795692
observation methods; momentary time sampling; partial interval recording; measurement error
2.  Are Expressive Suppression and Cognitive Reappraisal Associated with Stress-Related Symptoms? 
Behaviour research and therapy  2008;46(9):993-1000.
Emotion dysregulation is thought to be critical to the development of negative psychological outcomes. Gross (1998b) conceptualized the timing of regulation strategies as key to this relationship, with response-focused strategies, such as expressive suppression, as less effective and more detrimental compared to antecedent-focused ones, such as cognitive reappraisal. In the current study, we examined the relationship between reappraisal and expressive suppression and measures of psychopathology, particularly for stress-related reactions, in both undergraduate and trauma-exposed community samples of women. Generally, expressive suppression was associated with higher, and reappraisal with lower, self-reported stress-related symptoms. In particular, expressive suppression was associated with PTSD, anxiety, and depression symptoms in the trauma-exposed community sample, with rumination partially mediating this association. Finally, based on factor analysis, expressive suppression and cognitive reappraisal appear to be independent constructs. Overall, expressive suppression, much more so than cognitive reappraisal, may play an important role in the experience of stress-related symptoms. Further, given their independence, there are potentially relevant clinical implications, as interventions that shift one of these emotion regulation strategies may not lead to changes in the other.
PMCID: PMC2629793  PMID: 18687419
Emotion regulation; expressive suppression; reappraisal; trauma; stress
3.  Pharmacokinetic and Pharmacodynamic Modeling of Anidulafungin (LY303366): Reappraisal of Its Efficacy in Neutropenic Animal Models of Opportunistic Mycoses Using Optimal Plasma Sampling 
Antimicrobial Agents and Chemotherapy  2001;45(10):2845-2855.
The compartmental pharmacokinetics of anidulafungin (VER-002; formerly LY303366) in plasma were characterized with normal rabbits, and the relationships between drug concentrations and antifungal efficacy were assessed in clinically applicable infection models in persistently neutropenic animals. At intravenous dosages ranging from 0.1 to 20 mg/kg of body weight, anidulafungin demonstrated linear plasma pharmacokinetics that fitted best to a three-compartment open pharmacokinetic model. Following administration over 7 days, the mean (± standard error of the mean) peak plasma concentration (Cmax) increased from 0.46 ± 0.02 μg/ml at 0.1 mg/kg to 63.02 ± 2.93 μg/ml at 20 mg/kg, and the mean area under the concentration-time curve from 0 h to infinity (AUC0–∞) rose from 0.71 ± 0.04 to 208.80 ± 24.21 μg · h/ml. The mean apparent volume of distribution at steady state (Vss) ranged from 0.953 ± 0.05 to 1.636 ± 0.22 liter/kg (nonsignificant [NS]), and clearance ranged from 0.107 ± 0.01 to 0.149 ± 0.00 liter/kg/h (NS). Except for a significant prolongation of the terminal half-life and a trend toward an increased Vss at the higher end of the dosage range after multiple doses, no significant differences in pharmacokinetic parameters were noted in comparison to single-dose administration. Concentrations in tissue at trough after multiple dosing (0.1 to 10 mg/kg/day) were highest in lung and liver (0.85 ± 0.16 to 32.64 ± 2.03 and 0.32 ± 0.05 to 43.76 ± 1.62 μg/g, respectively), followed by spleen and kidney (0.24 ± 0.65 to 21.74 ± 1.86 and <0.20 to 16.92 ± 0.56, respectively). Measurable concentrations in brain tissue were found at dosages of ≥0.5 mg/kg (0.24 ± 0.02 to 3.90 ± 0.25). Implementation of optimal plasma sampling in persistently neutropenic rabbit infection models of disseminated candidiasis and pulmonary aspergillosis based on the Bayesian approach and model parameters from normal animals as priors revealed a significantly slower clearance (P < 0.05 for all dosage groups) with a trend toward higher AUC0–24 values, higher plasma concentrations at the end of the dosing interval, and a smaller volume of distribution (P < 0.05 to 0.193 for the various comparisons among dosage groups). Pharmacodynamic modeling using the residual fungal tissue burden in the main target sites as the primary endpoint and Cmax, AUC0–24, time during the dosing interval of 24 h with plasma drug concentration equaling or exceeding the MIC or the minimum fungicidal concentration for the isolate, and tissue concentrations as pharmacodynamic parameters showed predictable pharmacokinetic-pharmacodynamic relationships in experimental disseminated candidiasis that fitted well with an inhibitory sigmoid maximum effect pharmacodynamic model (r2, 0.492 to 0.819). However, no concentration-effect relationships were observed in experimental pulmonary aspergillosis using the residual fungal burden in lung tissue and survival as parameters of antifungal efficacy. Implementation of optimal plasma sampling in discriminative animal models of invasive fungal infections and pharmacodynamic modeling is a novel approach that holds promise of improving and accelerating our understanding of the action of antifungal compounds in vivo.
PMCID: PMC90741  PMID: 11557479
4.  The Kinetics of Intramolecular Distribution of 15N in Uric Acid after Administration of [15N]Glycine A REAPPRAISAL OF THE SIGNIFICANCE OF PREFERENTIAL LABELING OF N-(3 + 9) OF URIC ACID IN PRIMARY GOUT 
Journal of Clinical Investigation  1973;52(10):2468-2485.
The concept of an abnormality of glutamine metabolism in primary gout was first proposed on the basis of isotope data: when [15N]glycine was administered to gouty subjects, there was disproportionately great enrichment of N-(3 + 9) of uric acid, which derive from the amide-N of glutamine. An unduly high concentration of 15N in glutamine was postulated, and attributed to a hypothetical defect in catabolism of glutamine. Excess glutamine was proposed as the driving force of uric acid overproduction.
We have reexamined this proposition in four gouty subjects: one mild overproducer of uric acid with “idiopathic gout,” one marked overproducer with high-grade but “partial” hypoxanthine-guanine phosphoribosyl-transferase deficiency, and two extraordinary overproducers with superactive phosphoribosylpyrophosphate synthetases. In the last three, the driving force of excessive purine biosynthesis is a known surplus of α-5-phosphoribosyl-1-pyrophosphate. Disproportionately high labeling of N-(3 + 9) was present in all four gouty subjects, most marked in the most flamboyant overproducers. The precursor glucine pool was sampled by periodic administration of benzoic acid and isolation of urinary hippuric acid. Similarly, the precursor glutamine pool was sampled by periodic administration of phenylacetic acid and isolation of the amide-N of urinary phenylacetylglutamine. The time course of 15N enrichment of hippurate differed from that of the amide-N of glutamine. Whereas initial enrichment values of hippurate were very high, those of glutamine-amide-N were low, increasing to a maximum at about 3 h, and then declining less rapidly than those of hippurate. However, enrichment values of hippurate and of phenacetyl glutamine were normal in all of the gouty subjects studied. Thus, preferential enrichment of N-(3 + 9) in gouty overproducers given [15N]glycine does not necessarily reflect a specific abnormality of glutamine metabolism, but rather appears to be a kinetic phenomenon associated with accelerated purine biosynthesis per se.
In addition, greater enrichment of N-9 than of N-3 on days 1 and 2 provided suggestive evidence for a second pathway for synthesis of the initial precursor of purine biosynthesis, phosphoribosylamine, perhaps utilizing ammonia rather than the amide-N of glutamine as nitrogen donor. In this limited study, the activity of this potential second pathway did not appear to be selectively increased in gout.
PMCID: PMC302506  PMID: 4353999
5.  Lack of Support for the Association between Facial Shape and Aggression: A Reappraisal Based on a Worldwide Population Genetics Perspective 
PLoS ONE  2013;8(1):e52317.
Antisocial and criminal behaviors are multifactorial traits whose interpretation relies on multiple disciplines. Since these interpretations may have social, moral and legal implications, a constant review of the evidence is necessary before any scientific claim is considered as truth. A recent study proposed that men with wider faces relative to facial height (fWHR) are more likely to develop unethical behaviour mediated by a psychological sense of power. This research was based on reports suggesting that sexual dimorphism and selection would be responsible for a correlation between fWHR and aggression. Here we show that 4,960 individuals from 94 modern human populations belonging to a vast array of genetic and cultural contexts do not display significant amounts of fWHR sexual dimorphism. Further analyses using populations with associated ethnographical records as well as samples of male prisoners of the Mexico City Federal Penitentiary condemned by crimes of variable level of inter-personal aggression (homicide, robbery, and minor faults) did not show significant evidence, suggesting that populations/individuals with higher levels of bellicosity, aggressive behaviour, or power-mediated behaviour display greater fWHR. Finally, a regression analysis of fWHR on individual's fitness showed no significant correlation between this facial trait and reproductive success. Overall, our results suggest that facial attributes are poor predictors of aggressive behaviour, or at least, that sexual selection was weak enough to leave a signal on patterns of between- and within-sex and population facial variation.
PMCID: PMC3541377  PMID: 23326328
6.  A Reappraisal of the Role of Abscisic Acid and its Interaction with Auxin in Apical Dominance 
Annals of Botany  2006;98(4):891-897.
• Background and Aims Evidence from pea rms1, Arabidopsis max4 and petunia dad1 mutant studies suggest an unidentified carotenoid-derived/plastid-produced branching inhibitor which moves acropetally from the roots to the shoots and interacts with auxin in the control of apical dominance. Since the plant hormone, abscisic acid (ABA), known to inhibit some growth processes, is also carotenoid derived/plastid produced, and because there has been indirect evidence for its involvement with branching, a re-examination of the role of ABA in apical dominance is timely. Even though it has been determined that ABA probably is not the second messenger for auxin in apical dominance and is not the above-mentioned unidentified branching inhibitor, the similarity of their derivation suggests possible relationships and/or interactions.
• Methods The classic Thimann–Skoog auxin replacement test for apical dominance with auxin [0·5 % naphthalene acetic acid (NAA)] applied both apically and basally was combined in similar treatments with 1 % ABA in Ipomoea nil (Japanese Morning Glory), Solanum lycopersicum (Better Boy tomato) and Helianthus annuus (Mammoth Grey-striped Sunflower).
• Key Results Auxin, apically applied to the cut stem surface of decapitated shoots, strongly restored apical dominance in all three species, whereas the similar treatment with ABA did not. However, when ABA was applied basally, i.e. below the lateral bud of interest, there was a significant moderate repression of its outgrowth in Ipomoea and Solanum. There was also some additive repression when apical auxin and basal ABA treatments were combined in Ipomoea.
• Conclusion The finding that basally applied ABA is able partially to restore apical dominance via acropetal transport up the shoot suggests possible interactions between ABA, auxin and the unidentified carotenoid-derived branching inhibitor that justify further investigation.
PMCID: PMC2806172  PMID: 16882681
Abscisic acid; auxin; branching; apical dominance; branching inhibitor; decapitated shoot; Ipomoea nil; strain violet; Solanum lycopersicum; Helianthus annuus
7.  Reappraisal of the coupling interval of ventricular extrasystoles as an index of ectopic mechanisms 
British Heart Journal  1992;68(6):589-595.
Objective—A mathematical model of modulated ventricular parasystole based on the relation between the coupling interval and the preceding RR interval was developed in an attempt to distinguish between parasystolic automaticity and other mechanisms.
Mathematical model—The relation between the coupling interval and the preceding RR interval was examined by plotting the coupling interval of each extrasystole against the preceding RR interval (coupling interval/RR diagram). The coupling interval/RR diagrams obtained from simulations with various modulation modes suggested that the parasystolic mechanism was likely when the dots representing extrasystoles appeared as discrete clusters. In contrast, a linear horizontal accumulation of dots indicated a non-parasystolic mechanism.
Clinical observation—To verify the validity of the simulations, 24 hour electrocardiographic recordings from 60 patients with frequent ventricular extrasystoles (>1000/day) were analysed to determine whether the extrasystoles showed intrinsic periodicity. Intrinsic periodicity indicative of a parasystolic mechanism was seen in 14 (93%) of 15 patients in whom the coupling interval/RR diagram was characteristic of a parasystolic mechanism. When the coupling interval did not change (variability <200 ms) over a wide range of RR intervals (>700 ms) intrinsic periodicity was never identified (0/17). Parasystolic automaticity was the likely mechanism in 11 of the remaining 28 patients (39·3%) in whom coupling interval/RR diagrams were not definitive.
Conclusion—These data indicate that definite patterns of coupling interval/RR diagrams can be used to distinguish between parasystolic and non-parasystolic mechanisms.
PMCID: PMC1025690  PMID: 1281661
8.  Reappraisal of Metformin Efficacy in the Treatment of Type 2 Diabetes: A Meta-Analysis of Randomised Controlled Trials 
PLoS Medicine  2012;9(4):e1001204.
Catherine Cornu and colleagues performed a meta-analysis of randomised controlled trials of metformin efficacy on cardiovascular morbidity or mortality in patients with type 2 diabetes and showed that although metformin is considered the gold standard, its benefit/risk ratio remains uncertain.
The UK Prospective Diabetes Study showed that metformin decreases mortality compared to diet alone in overweight patients with type 2 diabetes mellitus. Since then, it has been the first-line treatment in overweight patients with type 2 diabetes. However, metformin-sulphonylurea bitherapy may increase mortality.
Methods and Findings
This meta-analysis of randomised controlled trials evaluated metformin efficacy (in studies of metformin versus diet alone, versus placebo, and versus no treatment; metformin as an add-on therapy; and metformin withdrawal) against cardiovascular morbidity or mortality in patients with type 2 diabetes. We searched Medline, Embase, and the Cochrane database. Primary end points were all-cause mortality and cardiovascular death. Secondary end points included all myocardial infarctions, all strokes, congestive heart failure, peripheral vascular disease, leg amputations, and microvascular complications. Thirteen randomised controlled trials (13,110 patients) were retrieved; 9,560 patients were given metformin, and 3,550 patients were given conventional treatment or placebo. Metformin did not significantly affect the primary outcomes all-cause mortality, risk ratio (RR) = 0.99 (95% CI: 0.75 to 1.31), and cardiovascular mortality, RR = 1.05 (95% CI: 0.67 to 1.64). The secondary outcomes were also unaffected by metformin treatment: all myocardial infarctions, RR = 0.90 (95% CI: 0.74 to 1.09); all strokes, RR = 0.76 (95% CI: 0.51 to 1.14); heart failure, RR = 1.03 (95% CI: 0.67 to 1.59); peripheral vascular disease, RR = 0.90 (95% CI: 0.46 to 1.78); leg amputations, RR = 1.04 (95% CI: 0.44 to 2.44); and microvascular complications, RR = 0.83 (95% CI: 0.59 to 1.17). For all-cause mortality and cardiovascular mortality, there was significant heterogeneity when including the UK Prospective Diabetes Study subgroups (I2 = 41% and 59%). There was significant interaction with sulphonylurea as a concomitant treatment for myocardial infarction (p = 0.10 and 0.02, respectively).
Although metformin is considered the gold standard, its benefit/risk ratio remains uncertain. We cannot exclude a 25% reduction or a 31% increase in all-cause mortality. We cannot exclude a 33% reduction or a 64% increase in cardiovascular mortality. Further studies are needed to clarify this situation.
Please see later in the article for the Editors' Summary
Editors' Summary
Worldwide, more than 350 million people have diabetes, and this number is increasing rapidly. Diabetes is characterized by dangerous amounts of sugar (glucose) in the blood. Blood sugar levels are normally controlled by insulin, a hormone produced by the pancreas. In people with type 2 diabetes (the most common form of diabetes), blood sugar control fails because the fat and muscle cells that usually respond to insulin by removing excess sugar from the blood become less responsive to insulin. Type 2 diabetes can be controlled with diet and exercise and with antidiabetic pills, each of which works in a different way to maintain a healthy blood sugar level. Metformin, for example, stops the liver making glucose and increases the body's response to insulin, whereas sulfonylureas help the pancreas make more insulin. The long-term complications of diabetes, which include an increased risk of cardiovascular problems such as heart disease and stroke, reduce the life expectancy of people with diabetes by about ten years compared to people without diabetes.
Why Was This Study Done?
In 1998, a large randomized clinical trial called the UK Prospective Diabetes Study (UKPDS 34) reported that metformin in combination with dietary control reduced all-cause mortality in overweight patients with type 2 diabetes when compared to dietary control alone. Specifically, the risk of death from any cause among patients taking metformin was about a third lower than the risk of death among patients not taking metformin—a risk ratio (RR) of 0.64. This reduction in risk was significant (that is, it was unlikely to have occurred by chance) because its 95% confidence interval (95% CI; there is a 95% chance that the “true” RR lies within this interval) of 0.45–0.91 did not overlap 1.0. Given this finding, metformin is now recommended as the first-line treatment for type 2 diabetes. However, UKPDS 34 also reported an increase in death in non-overweight patients who took metformin plus sulfonylurea compared to those who took sulfonylurea alone (RR: 1.60; 95% CI: 1.02–2.52), a result considered non-significant by the UKPDS 34 researchers and largely ignored ever since. So do the benefits of metformin outweigh its risks? In this meta-analysis, the researchers re-evaluate the risk-to-benefit balance of metformin in the treatment of patients with type 2 diabetes. A meta-analysis is a statistical method that combines the results of several studies.
What Did the Researchers Do and Find?
The researchers identified 13 randomized controlled trials that evaluated the effect of metformin on cardiovascular morbidity (illness) and mortality in patients with type 2 diabetes. More than 13,000 patients participated in these studies, three-quarters of whom received metformin and a quarter of whom received other treatments or a placebo. Compared to other treatments, metformin treatment had no effect on the risk of all-cause mortality (RR: 0.99; 95% CI: 0.75–1.31) or cardiovascular mortality (RR: 1.05; 95% CI: 0.67–1.64), the primary end points of this study. However, the results of the individual trials varied more than would be expected by chance (“heterogeneity”). Exclusion of the UKPDS 34 trial from the meta-analysis had no effect on the estimated risk ratio for all-cause mortality or cardiovascular deaths, but the heterogeneity disappeared. Finally, metformin treatment had no significant effect on the risk of cardiovascular conditions such as heart attacks, strokes, and heart failure; there was no heterogeneity among the trials for these secondary end points.
What Do These Findings Mean?
These findings show no evidence that metformin has any beneficial effect on all-cause mortality, on cardiovascular mortality, or on cardiovascular morbidity among patients with type 2 diabetes. These findings must be cautiously interpreted because only a few randomized controlled trials were included in this study, and only a few patients died or developed any cardiovascular illnesses. Importantly, however, from these findings, it is impossible to exclude beyond reasonable doubt the possibility that metformin causes up to a 25% reduction or a 31% increase in all-cause mortality. Similarly, these findings cannot exclude the possibility that metformin causes up to a 33% reduction or a 64% increase in cardiovascular mortality. Given that a large number of patients take metformin for many years as a first-line treatment for diabetes, further studies are urgently needed to clarify this situation.
Additional Information
Please access these web sites via the online version of this summary at
The International Diabetes Federation provides information about all aspects of diabetes
The US National Diabetes Information Clearinghouse provides information about diabetes for patients, health-care professionals, and the general public, including detailed information on diabetes medicines (in English and Spanish)
The UK National Health Service Choices web site provides information for patients and carers about type 2 diabetes and includes peoples stories about diabetes
The charity Diabetes UK also provides detailed information for patients and carers, including information on diabetes medications, and has a further selection of stories from people with diabetes
MedlinePlus provides links to further resources and advice about diabetes and about diabetes medicines; it also provides information about metformin (in English and Spanish)
The charity Healthtalkonline has interviews with people about their experiences of diabetes and of controlling diabetes with oral medications
PMCID: PMC3323508  PMID: 22509138
9.  Reappraisal of thyroxine treatment in primary hypothyroidism. 
Archives of Disease in Childhood  1990;65(10):1129-1132.
The optimum daily dose of thyroxine was calculated for 13 children aged 3-16 years with primary hypothyroidism by titrating their doses at monthly intervals. The condition of the thyroid was assessed by sensitive assay of thyroid stimulating hormone concentrations, as well as measurement of total and free thyroid hormone concentrations and systolic time interval ratios. Serum thyroid stimulating hormone concentration was found to be the most responsive to small changes in thyroxine. The calculated optimum daily replacement dose of thyroxine (102 micrograms/m2 or 3.5 micrograms/kg) was fractionally lower than that previously recommended, and was more closely related to surface area (coefficient of variation 8.2%) than to body weight (coefficient of variation 16.2%). Our results suggest that though monthly may be the optimal time interval for increases in the dose of thyroxine, any reduction in the dose should be made more gradually.
PMCID: PMC1792337  PMID: 2248504
10.  Reappraising suppression: subjective and physiological correlates of experiential suppression in healthy adults 
Background: Emotion regulation strategies based on suppressing behavioral expressions of emotion have been considered maladaptive. However, this may not apply to suppressing the emotional experience (experiential suppression). The aim of this study was to define the effect of experiential suppression on subjective and physiological emotional responses.
Methods: Healthy adults (N = 101) were characterized in terms of the temperament, personality, and hedonic capacity using the Tridimensional Personality Questionnaire, the Eysenck Personality Questionnaire, the Fawcett–Clark Pleasure Scale, and the State-Trait Anxiety Inventory. Participants were shown positive, negative, and neutral pictures from the International Affective Picture System under two conditions, passive viewing, and experiential suppression. During both conditions, subjective ratings of the intensity and duration of emotional responses and physiological measures of skin conductance (SC) and cardiac inter-beat interval (IBI) to each picture were recorded.
Results: Negative pictures elicited the most intense physiological and emotional responses regardless of experimental condition. Ratings of emotional intensity were not affected by condition. In contrast, experiential suppression, compared to passive viewing, was associated with decreased duration of the emotional response, reduced maximum SC amplitude and longer IBIs independent of age, picture valence, personality traits, hedonic capacity, and anxiety.
Conclusion: These findings demonstrate that experiential suppression may represent an adaptive emotion regulation mechanism associated with reduced arousal and cardiovascular activation.
PMCID: PMC4052820  PMID: 24966844
emotion regulation; experiential suppression; skin conductance response; heart rate; time course
11.  Reappraising the Long-term Course and Outcome of Psychotic Disorders 
Psychological medicine  2014;44(13):2713-2726.
Studies of the long-term course and outcome of psychoses tend to focus on cohorts of prevalent cases. Such studies bias samples toward those with poor outcomes, which may distort our understanding of prognosis. Long-term follow-up studies of epidemiologically robust first-episode samples are rare.
ÆSOP-10 is a ten-year follow-up of 557 individuals with a first-episode of psychosis initially identified in two areas in the UK (south-east London and Nottingham). Detailed information was collated on course and outcome in three domains (clinical, social, service use) from case records, informants and follow-up interviews.
At follow-up: 37 (7%) cases had died, 29 (6%) had emigrated, and 8 (2%) were excluded. Of the remaining 458, 412 (90%) were traced and some information on follow-up was collated for 387 (85%). Most cases (265, 77%) experienced at least one period of sustained remission; at follow-up, 141 (46%) had been symptom free for two or more years. A majority (208, 72%) of cases had been employed for less than 25% of the follow-up. The median number of hospital admissions, including at first presentation, was 2 (IQR 1-4); a majority (299, 88%) were admitted a least once and a minority (21, 6%) had 10 or more admissions. Overall, outcomes were worse for those with a non-affective diagnosis, for men and for those from London.
Sustained periods of symptom remission are usual following first presentation to mental health services for psychosis, including for those with a non-affective disorder; almost half recover.
PMCID: PMC4134320  PMID: 25066181
12.  Reappraisal of sexually transmitted infections in children: A hospital-based study from an urban area 
Sexually transmitted diseases (STDs) in children can be acquired either by sexual, or non-sexual route. Sexually transmitted infection (STI) in children reflect the pattern of STI in adult population and the knowledge, attitude and practices of the society. They also serve as an indicator of STI control strategies.
A retrospective study spanning over a period of 5 years from 2007 to 2011) was undertaken to make a detailed analysis of demographic, behavioral, epidemiological and clinical profile of STD among children (<19 years).
Materials and Methods:
The medical records of children attending the STI clinic of Smt. Sucheta Kriplani Hospital from year 2007 to 2011 were studied. Results of Gram's staining, KOH examination, Tzanck smear, culture and serological tests like Venereal Disease Research Laboratory for syphilis and ELISA for human immunodeficiency virus (HIV) wherever performed were recorded along with the final diagnosis.
The study showed a steady rise in the prevalence of STIs from 1% to 4.9% in the initial 4 years. STIs were more commonly observed in girls (M:F ratio - 1:1.13) and in adolescents >16 years of age. Homosexuality was present in 33.3% of males. History of sexual abuse was given by 4 children. 2 children were seropositive for HIV by ELISA technique. Viral STIs (Cyanea acuminata, molluscum contagiosum, herpes genitalis) were 1.5 times more common than bacterial infections.
The societal sexual practices have undergone tremendous changes, which is reflected in a steady rise in STIs (predominantly viral), sexual abuse and homosexuality in children. There is an urgent need for strengthening of school health programs aiming at adolescent sexual health.
PMCID: PMC4066593  PMID: 24958982
Children; sexually transmitted diseases; sexually transmitted infections
13.  The Wyckoff observing response—a reappraisal1 
Pigeons were trained on a Wyckoff observing response procedure in which key responses were reinforced on a mixed schedule consisting of fixed-interval and extinction components. In Experiment 1, stepping on a pedal (a) converted the mixed schedule to a multiple schedule, (b) replaced the mixed-schedule stimulus with an unlit key (or, in different phases, a blackout), or (c) had no consequence. In Experiment 2, pedal standing removed the mixed-schedule stimulus that was physically similar to the multiple-schedule stimuli or one that was less similar. In Experiment 3, Wyckoff's differential and nondifferential discrimination procedure was repeated. The results of Experiments 1 and 2 showed that the Wyckoff pedal response was controlled by neither the removal of the mixed-schedule stimulus nor the production of discriminative stimuli. The results indicated a correlation between key-response rates and pedal-standing time. Experiment 3 showed that high response rates to mixed-schedule stimuli were correlated with little pedal-standing time while high key-response rates to multiple-schedule stimuli were correlated with considerable pedal standing time. The correlation between key-response rates and pedal-standing time was related to the physical arrangement between the key and pedal operanda.
PMCID: PMC1334011  PMID: 16811630
14.  Decentering as a Common Link among Mindfulness, Cognitive Reappraisal, and Social Anxiety 
The tendency to employ both cognitive reappraisal and mindfulness are associated with reduced trait social anxiety; however, it is unclear whether reappraisal and mindfulness are associated with social anxiety through the same mechanisms. It has been proposed that decentering, or the process of seeing thoughts or feelings as objective events in the mind rather than personally identifying with them, may be a key mechanism underlying both cognitive reappraisal and mindfulness.
To examine the relationships between reappraisal, mindfulness, decentering, and social anxiety.
This study utilized structural equation modeling to examine the relationships among cognitive reappraisal, mindfulness, decentering, and social anxiety in a large cross-sectional study.
Results indicate that the relationship between mindfulness and social anxiety is partially accounted for by decentering, whereas the relationship between cognitive reappraisal and social anxiety is more fully accounted for by decentering.
These results imply that decentering may be a common mechanism underlying both cognitive reappraisal and mindfulness, although mindfulness may also affect social anxiety through additional mechanisms. However, given the cross-sectional nature of these findings, results should be considered preliminary with future research being needed to further elucidate these relationships.
PMCID: PMC3756689  PMID: 23218023
15.  Reappraisal of thienopyridine pretreatment in patients with non-ST elevation acute coronary syndrome: a systematic review and meta-analysis 
Objective To investigate the effect of pretreatment with P2Y12 receptor inhibitors compared with no pretreatment on efficacy and safety of treatment of non-ST elevation acute coronary syndrome (ACS).
Data sources Two reviewers independently searched Medline, Embase, Cochrane Controlled Trials, and BioMed Central databases for randomized placebo controlled trials and observational studies from August 2001 to March 2014.
Study eligibility Studies must have reported both all-cause mortality (primary efficacy endpoint) and major bleeding (safety endpoint) outcomes.
Data extraction Data on sample size, characteristics, drug dose and delay of administration, and outcomes were independently extracted and analyzed.
Data synthesis A random-effect model was applied. The analysis was performed (i) in all patients independently of the management strategy and (ii) only in patients undergoing percutaneous coronary intervention.
Results Of the 393 titles identified, seven (four randomized controlled trials, one observational analysis from a randomized controlled trial, and three observational studies) met the inclusion criteria. No study was identified for ticagrelor or cangrelor, and analyses were thus limited to thienopyridines. A total of 32 383 non-ST elevation ACS patients were included, 18 711 coming from randomized controlled trials. Of these, 55% underwent percutaneous coronary intervention (PCI). Pretreatment was not associated with a significant lower risk of mortality in all patients (odds ratio 0.90 (95% confidence interval 0.75 to 1.07), P=0.24), in particular when considering only the randomized controlled trials (odds ratio 0.90 (0.71 to 1.14), P=0.39). Similar results were observed in the cohort of patients undergoing PCI. A significant 30-45% excess of major bleeding was consistently observed in all patients (odds ratio 1.32 (1.16 to 1.49), P<0.0001) and in those undergoing PCI, as well as in the subset analyses of randomized controlled trials of these two cohorts of patients. There was a reduction in major adverse cardiovascular events in the analysis of all patients (odds ratio 0.84 (0.72 to 0.98), P=0.02), driven by the old clopidogrel studies (CURE and CREDO), but the difference was not significant for the cohort of patients undergoing PCI. Stent thrombosis, stroke, and urgent revascularization did not differ between groups (pretreatment v no pretreatment). The results were consistent for both thienopyridines and confirmed in sensitivity analyses.
Limitations Analysis was not performed on individual patient’s data.
Conclusion In patients presenting with non-ST elevation ACS, pretreatment with thienopyridines is associated with no significant reduction of mortality but with a significant excess of major bleeding no matter the strategy adopted, invasive or not. Our results do not support a strategy of routine pretreatment in patients with non-ST elevation ACS.
PMCID: PMC4208629
16.  Reappraisal of bicarbonate secretion by the human oesophagus. 
Gut  1997;40(5):582-586.
BACKGROUND AND AIMS: Administration of omeprazole to healthy volunteers was recently reported to increase proximal duodenal mucosal bicarbonate secretion. As human oesophagus also secretes bicarbonate, the hypothesis was tested that omeprazole may stimulate oesophageal bicarbonate secretion and thus contribute to the therapeutic efficacy of the drug in gastro-oesophageal reflux disease. SUBJECTS AND METHODS: In nine healthy volunteers, oesophageal "steady state" perfusion of a 10 cm open segment of distal oesophagus was performed twice in random order. The volunteers were pretreated with either 60 mg/day omeprazole for three days and 80 mg intravenous omeprazole before perfusion or 600 mg/day ranitidine for three days and 50 mg/h intravenously during the perfusion. Saliva and samples of aspirate from the perfused oesophagus and stomach were collected and bicarbonate concentrations were measured. RESULTS: The median rates (95% confidence intervals) of intrinsic oesophageal bicarbonate secretion, corrected for contaminating salivary and gastric bicarbonate, were 89 (33-150) and 121 (63-203) mumol/h/10 cm (p > 0.5) in omeprazole and ranitidine treated subjects respectively. Salivary and gastric bicarbonate contaminating the oesophagus accounted for 14% and 3%, respectively, of total oesophageal bicarbonate output. CONCLUSIONS: Bicarbonate secretory capacity of the human oesophagus is less than previously assumed, and the clinical relevance of intrinsic oesophageal bicarbonate for mucosal defence may be overestimated. As omeprazole and ranitidine did not affect bicarbonate secretion differently there was no evidence that omeprazole acts on bicarbonate secretory cells in the oesophageal mucosa.
PMCID: PMC1027157  PMID: 9203933
17.  Microvascular Invasion Does Not Predict Long-Term Survival in Hepatocellular Carcinoma up to 2 cm: Reappraisal of the Staging System for Solitary Tumors 
Annals of surgical oncology  2012;20(4):10.1245/s10434-012-2739-y.
Excellent long-term outcomes have been reported recently for patients with small (≤2 cm) hepatocellular carcinoma (HCC). However, the significance of microvascular invasion (MVI) in small HCC remains unclear. The purpose of this study was to determine the impact of MVI in small HCC up to 2 cm.
In 1,109 patients with solitary HCC from six major international hepatobiliary centers, the impact of MVI on long-term survival in patients with small HCC (≤2 cm) and patients with tumors larger than 2 cm was analyzed.
In patients with small HCC, long-term survival was not affected by MVI (p = 0.8), whereas in patients with larger HCC, significantly worse survival was observed in patients with MVI (p < 0.0001). In multivariate analysis, MVI (hazard ratio [HR] 1.59; 95 % confidence interval (CI) 1.27–1.99; p < 0.001), elevated alpha-fetoprotein (HR 1.41; 95 % CI 1.11–1.8; p = 0.005), and higher histologic grade (HR 1.29; 95 % CI 1.01–1.64; p = 0.04) were significant predictors of worse survival in patients with HCC larger than 2 cm but were not correlated with long-term survival in small HCC. When the cohort was divided into three groups—HCC ≤2, >2 cm without MVI, and HCC >2 cm with MVI—significant between-group survival difference was observed (p < 0.0001).
Small HCC is associated with an excellent prognosis that is not affected by the presence of MVI. The discriminatory power of the 7th edition of the AJCC classification for solitary HCC could be further improved by subdividing tumors according to size (≤2 vs. >2 cm).
PMCID: PMC3856190  PMID: 23179993
18.  Turning the knots in your stomach into bows: Reappraising arousal improves performance on the GRE 
This research examined the benefits of interpreting physiological arousal as a challenge response on practice and actual Graduate Record Examination (GRE) scores. Participants who were preparing to take the GRE reported to the laboratory for a practice GRE study. Participants assigned to a reappraisal condition were told arousal improves performance, whereas control participants were not given this information. We collected saliva samples at baseline and after the appraisal manipulation, which were then assayed for salivary alpha amylase (sAA), a measure of sympathetic nervous system activation. Reappraisal participants exhibited a significant increase in sAA and outperformed controls on the GRE-math section. One to three months later, participants returned to the lab and provided their score reports from their actual GRE. Again, reappraisal participants scored higher than controls on the GRE-math section. These findings illuminate the powerful influence appraisal has on physiology and performance both in and out of the laboratory.
PMCID: PMC2790291  PMID: 20161454
19.  Reappraising the concept of massive transfusion in trauma 
Critical Care  2010;14(6):R239.
The massive-transfusion concept was introduced to recognize the dilutional complications resulting from large volumes of packed red blood cells (PRBCs). Definitions of massive transfusion vary and lack supporting clinical evidence. Damage-control resuscitation regimens of modern trauma care are targeted to the early correction of acute traumatic coagulopathy. The aim of this study was to identify a clinically relevant definition of trauma massive transfusion based on clinical outcomes. We also examined whether the concept was useful in that early prediction of massive transfusion requirements could allow early activation of blood bank protocols.
Datasets on trauma admissions over a 1 or 2-year period were obtained from the trauma registries of five large trauma research networks. A fractional polynomial was used to model the transfusion-associated probability of death. A logistic regression model for the prediction of massive transfusion, defined as 10 or more units of red cell transfusions, was developed.
In total, 5,693 patient records were available for analysis. Mortality increased as transfusion requirements increased, but the model indicated no threshold effect. Mortality was 9% in patients who received none to five PRBC units, 22% in patients receiving six to nine PRBC units, and 42% in patients receiving 10 or more units. A logistic model for prediction of massive transfusion was developed and validated at multiple sites but achieved only moderate performance. The area under the receiver operating characteristic curve was 0.81, with specificity of only 50% at a sensitivity of 90% for the prediction of 10 or more PRBC units. Performance varied widely at different trauma centers, with specificity varying from 48% to 91%.
No threshold for definition exists at which a massive transfusion specifically results in worse outcomes. Even with a large sample size across multiple trauma datasets, it was not possible to develop a transportable and clinically useful prediction model based on available admission parameters. Massive transfusion as a concept in trauma has limited utility, and emphasis should be placed on identifying patients with massive hemorrhage and acute traumatic coagulopathy.
PMCID: PMC3219977  PMID: 21192812
20.  An Epidemiological Reappraisal of the Familial Aggregation of Prostate Cancer: A Meta-Analysis 
PLoS ONE  2011;6(10):e27130.
Studies on familial aggregation of cancer may suggest an overall contribution of inherited genes or a shared environment in the development of malignant disease. We performed a meta-analysis on familial clustering of prostate cancer. Out of 74 studies reporting data on familial aggregation of prostate cancer in unselected populations retrieved by a Pubmed search and browsing references, 33 independent studies meeting the inclusion criteria were used in the analysis performed with the random effects model. The pooled rate ratio (RR) for first-degree family history, i.e. affected father or brother, is 2.48 (95% confidence interval: 2.25–2.74). The incidence rate for men who have a brother who got prostate cancer increases 3.14 times (CI:2.37–4.15), and for those with affected father 2.35 times (CI:2.02–2.72). The pooled estimate of RR for two or more affected first-degree family members relative to no history in father and in brother is 4.39 (CI:2.61–7.39). First-degree family history appears to increase the incidence rate of prostate cancer more in men under 65 (RR:2.87, CI:2.21–3.74), than in men aged 65 and older (RR:1.92, CI:1.49–2.47), p for interaction = 0.002. The attributable fraction among those having an affected first-degree relative equals to 59.7% (CI:55.6–63.5%) for men at all ages, 65.2% (CI:57.7–71.4%) for men younger than 65 and 47.9% (CI:37.1–56.8%) for men aged 65 or older. For those with a family history in 2 or more first-degree family members 77.2% (CI:65.4–85.0%) of prostate cancer incidence can be attributed to the familial clustering. Our combined estimates show strong familial clustering and a significant effect-modification by age meaning that familial aggregation was associated with earlier disease onset (before age 65).
PMCID: PMC3205054  PMID: 22073129
21.  Undermatching: a reappraisal of performance on concurrent variable-interval schedules of reinforcement1 
The extant data for pigeons' performance on concurrent variable-interval schedules were examined in detail. Least-squares lines relating relative pecks and time to the corresponding relative reinforcements were obtained for four studies. The between-study group slopes for time and pecks and five of seven within-study group slopes from individual studies were less than 1.00. This suggested the generality that pigeons respond less to the richer reinforcement schedule than predicted by matching. For pecks, a nonparametric test for distribution of points also supported this concept of undermatching (to the richer reinforcement schedule). In addition, using mean squared error as the criterion, a cubic curve fit the peck proportion data better than any line or other polynomial. This indicates that the relation between peck and reinforcement proportions may be nonlinear.
PMCID: PMC1333565  PMID: 16811977
undermatching concurrent variable-interval schedules; matching; pigeons
22.  Reappraisal of the Etiology of Extracorpuscular Non-Autoimmune Acquired Hemolytic Anemia in 2657 Hospitalized Patients with Non-Neoplastic Disease 
Unlike autoimmune hemolytic anemia (AIHA), literature on the etiological study of non-autoimmune hemolytic anemia (non-AIHA) is scarce. The incidence and prevalence of non-AIHA in different geographic regions are largely unknown perhaps owing to the lack of perspective investigation and different profiles of etiologies from different geographic regions. We aimed to examine the real-world etiology or mechanisms of the non-hereditary non-AIHA from a nationwide population-based administrative claim database in Taiwan.
The National Health Insurance Research Database of Taiwan was adopted for this research. The studied population was total inpatient claim records including both pediatric and adult patients, contributed by a population of 23 million insured individuals in Taiwan. From 2002 to 2008, we retrieved 3,903 patients having no pre-existing malignancy discharged after inpatient management for acquired hemolytic anemia, which was defined as coding in discharge diagnoses containing ICD-9-CM code 283. By contrast, ICD-9-CM code 282 and all of the sub-codes are for hereditary hemolytic anemias.
AIHA accounted for 32% of the total cases. Among 2,657 patients with non-AIHA, mechanical or microangiopathic mechanism accounted for 19% of cases; hemolytic-uremic syndrome (HUS) 4%, hemoglobinuria because of hemolysis from external causes such as paroxysmal nocturnal hemoglobinuria (PNH) and march hemoglobinuria 7%, and chronic idiopathic hemolytic anemia or other unspecified non-AIHA 69%. We looked further for specific etiology or mechanism for this group of patients with non-hereditary extrinsic non-AIHA (n = 2,657). The explanatory disease states or conditions were splenomegaly; alcohol use disorder (spur cell hemolysis); heart-valve prosthesis; malignant hypertension; disseminated intravascular coagulation; transfusion reaction; dengue fever-induced hemolytic anemia; direct parasitization; snake, lizard, or spider bite; and Wilson’s disease with internal toxin mechanism. All these cases can explain up to 34.6% of all the non-hereditary extrinsic non-AIHA cases. Fragmentation hemolysis (HUS, heart-valve prosthesis, malignant hypertension, and disseminated intravascular coagulation) accounted for 7.4% of non-AIHA hospitalized patients with non-neoplastic disease.
This article is the first one to clearly demonstrate that the non-neoplastic-induced HUS requiring hospitalization cases in Taiwan, which has a population of over 23 million were 110 over a span of seven years, 16 cases per year. Although the etiologies of non-AIHA are well known and described in the literature, this work added the statistical percentages of the various etiologies of non-AIHA in Taiwan.
PMCID: PMC3999811  PMID: 24808725
non-immune hemolytic anemia; anemia; hemolytic; etiology; causality; extracorpuscular; hospitalized; NHIRD
23.  Reappraisal of the chloride plate test as screening test for cystic fibrosis. 
Archives of Disease in Childhood  1981;56(2):137-139.
A rapid and simple screening test for detecting cystic fibrosis, described in 1956, has been used routinely for 21 years; the results during a 15-month period are compared with those using the quantitative pilocarpine iontophoresis sweat test. In the chloride agar plate test the concentration of chloride on the finger tips is evaluated accordingly to the intensity of the imprint. Readings of 2+ or less excluded cystic fibrosis in 1589 cases with only two doubtful instances, whereas 4+ readings were recorded in 198 cases of cystic fibrosis and 3+ readings in 15 cases of cystic fibrosis. In doubtful cases 4 individuals had 4+ readings and 11 had 3+ readings. This screening test does not replace the quantitative pilocarpine iontophoresis test but it does identify an individual who is likely to have the disease and who requires further tests. It is not reliable for infants aged under 2 months.
PMCID: PMC1627134  PMID: 7469466
24.  Reappraisal of Spontaneous Closure Rate of Idiopathic Full-Thickness Macular Holes 
We retrospectively reviewed the records of 142 eyes of 138 patients with idiopathic full-thickness macular hole. Spontaneous closure of idiopathic full-thickness macular hole was observed in five eyes (3.5%) of four patients before the planned vitrectomy. In the era when surgical treatment was not available for macular hole, the rate of spontaneous closure of idiopathic full-thickness macular hole was reported as 6.2%. Among several case reports on spontaneous closure of idiopathic full-thickness macular hole based on the optical coherence tomography images only one study reported the rate of spontaneous closure as 2.7%. According to the previous reports and our results, small idiopathic full-thickness macular holes may close spontaneously in a few percent of all macular hole cases. The rate of spontaneous closure may be affected by the waiting time before vitrectomy.
PMCID: PMC3428785  PMID: 22934124
Full-thickness macular hole; spontaneous closure; optical coherence tomography.
25.  Reappraising the Surgical Approach on the Perforated Gastroduodenal Ulcer: Should Gastric Resection Be Abandoned? 
Advancements in medical care for peptic ulcer disease (PUD) have reduced the need for invasive surgical procedures such as gastric resection (GR). Community-based PUD studies from a large sampling of PUD patients designed to analyze hospital resource use and outcomes after different surgical procedures have been rare. We aimed to exhaustively reappraise the risk factors and patient demographics that affect PUD patient recoveries after GR compared to those after simple closure (SC).
We used a Japanese administrative database for 6 consecutive months each year between 2006 and 2010. The database included a total of 68,432 PUD patients; we analyzed 6,334 perforation cases and 3,148 cases of patients who underwent GR or SC. Study variables were demographics, comorbidities, characteristics of PUD, and operative day. Study outcomes that were analyzed included mortality, postoperative complications, ventilation administration, postoperative blood transfusions, length of stay, total charges, operating room (OR) time, and the postoperative fasting period (defined as the day of surgery to the day oral food intake was resumed.) To reduce selection bias in study procedures and to control the variation in hospital practice, a propensity score (PS) matching cohort analysis and a mixed linear regression model were used to assess the effects of GR on the outcomes.
In 699 hospitals, 322 GRs and 2,826 SCs were observed. Younger age, duodenal ulcers, preexisting anemia and an operative day no more than 24hours were significant associated with the choice of SCs. No significant differences were observed in study outcomes after either GR or SC; more postoperative blood transfusions and longer OR times but shorter postoperative fasting periods were observed after GR. Longer OR times, ventilation and postoperative blood transfusion were significantly associated with mortality. Not GR but longer OR times use of ventilation and complications were the most significant indicators of increased resource use.
There were no major significant differences in GR when compared to SC with regards to patient recoveries. Surgeons should obtain the skills and establish strategies to optimize either type of surgical procedure including minimizing OR time and establishing the best perioperative critical care.
Peptic ulcer perforation; Simple closure; Gastric resection; Outcome; Resource use
PMCID: PMC3279482  PMID: 22383908

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