The authors previously demonstrated significant association between markers within NOS1AP and schizophrenia in a set of Canadian families of European descent, as well as significantly increased expression in schizophrenia of NOS1AP in unrelated postmortem samples from the dorsolateral prefrontal cortex. In this study the authors sought to apply novel statistical methods and conduct additional biological experiments to isolate at least one risk allele within NOS1AP.
Using the posterior probability of linkage disequilibrium (PPLD) to measure the probability that a single nucleotide polymorphism (SNP) is in linkage disequilibrium with schizophrenia, the authors evaluated 60 SNPs from NOS1AP in 24 Canadian families demonstrating linkage and association to this region. SNPs exhibiting strong evidence of linkage disequilibrium were tested for regulatory function by luciferase reporter assay. Two human neural cell lines (SK-N-MC and PFSK-1) were transfected with a vector containing each allelic variant of the SNP, the NOS1AP promoter, and a luciferase gene. Alleles altering expression were further assessed for binding of nuclear proteins by electrophoretic mobility shift assay.
Three SNPs produced PPLDs >40%. One of them, rs12742393, demonstrated significant allelic expression differences in both cell lines tested. The allelic variation at this SNP altered the affinity of nuclear protein binding to this region of DNA.
The A allele of rs12742393 appears to be a risk allele associated with schizophrenia that acts by enhancing transcription factor binding and increasing gene expression.
PMID: 19255043 CAMSID: cams2101
The authors report on the use of the DSM-III, several years after its introduction, in the clinical diagnosis of 154 subjects with first onset psychosis. Clinicians usually assigned Axis I diagnoses but used the remainder of the multiaxial system less than one time in three; if a standard recording form was in place, the multiaxial system was used more often. Trainees used the DSM-III most, followed by psychiatrists affiliated with a university and community based clinicians. Agreement between researchers and clinicians on diagnoses was fair to poor. The authors discuss the implications of the acceptance of the complex diagnostic system in routine clinical practice.
PMID: 1868420 CAMSID: cams1957
It remains unclear whether age at onset for major psychiatric disorders is a useful marker of etiologic and genetic heterogeneity. The authors examined how heritability of schizophrenia and major affective disorders varied with age at onset. The sample was drawn from a large archival data set collected by Lionel Penrose, comprising 3,109 families with two or more members first hospitalized in Ontario between 1874 and 1944. The authors studied 1,295 sibships with schizophrenia (n = 487), major affective disorder (n = 378), both (n = 234) or neither (n = 196) of these disorders. Proportional hazards models were used to estimate how the hazard of hospitalization for each disorder (schizophrenia or major affective disorder) varied with proband age at onset, adjusted for changes in age at onset distribution between 1874 and 1944. A sibling’s risk of hospitalization for the same illness significantly increased for each 10-year decrease in age at onset of the proband both for schizophrenia (hazard ratio = 1.21, 95 % confidence interval: 1.06, 1.39), and for affective disorder (hazard ratio = 1.29, 95 % CI: 1.14,1.45). Gender of proband was unrelated to sibling risk of the same illness, and tests of interaction effects between proband age at onset and gender on sibling risk were nonsignificant.
PMID: 16331352 CAMSID: cams1793
age of onset; cohort effect; mood disorders; schizophrenia; heredity
An HIV preventive intervention targeting the sex work milieu and involving fully integrated components of structural interventions (SI), communication for behavioural change and care for sexually transmitted infections (STI), was implemented in Benin by a Canadian project from 1992 to 2006. It first covered Cotonou before being extended to other main cities from 2000. At the project end, the Beninese authorities took over the intervention, but SI were interrupted and other intervention components were implemented separately. We estimated time trends in HIV/STI prevalence among female sex workers (FSW) from 1993 to 2008 and assessed the impact of the change in intervention model on trends.
Six integrated biological and behavioural surveys were carried out among FSW. Time trend analysis controlled for potential socio-demographic confounders using log-binomial regression.
In Cotonou, from 1993 to 2008, there was a significant decrease in HIV (53.3 to 30.4%), gonorrhea (43.2 to 6.4%) and chlamydia (9.4 to 2.8%) prevalence (all adjusted-p=0.0001). The decrease in HIV and gonorrhea prevalence was also significant in the other cities between 2002 and 2008. In 2002, gonorrhea prevalence was lower in Cotonou than elsewhere (prevalence ratio [PR]=0.53; 95% confidence interval [95%CI]: 0.32–0.88). From 2005 to 2008, there was an increase in gonorrhea prevalence (PR=1.76; 95%CI: 1.17–2.65) in all cities combined.
Our results suggest a significant impact of this targeted preventive intervention on HIV/STI prevalence among FSW. The recent increase in gonorrhea prevalence could be related to the lack of integration of the intervention components.
PMID: 23337368 CAMSID: cams3496
Restricted feeding (RF) schedules are potent zeitgebers capable of entraining metabolic and hormonal rhythms in peripheral oscillators in anticipation of food. Behaviorally, this manifests in the form of food anticipatory activity (FAA) in the hours preceding food availability. Circadian rhythms of FAA are thought to be controlled by a food-entrainable oscillator (FEO) outside of the suprachiasmatic nucleus (SCN), the central circadian pacemaker in mammals. Although evidence suggests that the FEO and the SCN are capable of interacting functionally under RF conditions, the genetic basis of these interactions remains to be defined. In this study, using dexras1-deficient (dexras1−/−) mice, the authors examined whether Dexras1, a modulator of multiple inputs to the SCN, plays a role in regulating the effects of RF on activity rhythms and gene expression in the SCN. Daytime RF under 12L:12D or constant darkness (DD) resulted in potentiated (but less stable) FAA expression in dexras1−/− mice compared with wild-type (WT) controls. Under these conditions, the magnitude and phase of the SCN-driven activity component were greatly perturbed in the mutants. Restoration to ad libitum (AL) feeding revealed a stable phase displacement of the SCN-driven activity component of dexras1−/− mice by ~2 h in advance of the expected time. RF in the late night/early morning induced a long-lasting increase in the period of the SCN-driven activity component in the mutants but not the WT. At the molecular level, daytime RF advanced the rhythm of PER1, PER2, and pERK expression in the mutant SCN without having any effect in the WT. Collectively, these results indicate that the absence of Dexras1 sensitizes the SCN to perturbations resulting from restricted feeding.
PMID: 22928915 CAMSID: cams3043
Circadian rhythms; Coupling; Dexras1; MAPK signaling; Period genes; Suprachiasmatic nucleus; Temporal restricted feeding
Inequalities in access to palliative care programs (PCP) by age have been shown to exist in Canada and elsewhere. Few studies have been able to provide greater insight by simultaneously adjusting for multiple demographic, health service, and socio-cultural indicators.
To re-examine the relationship between age and registration to specialized community-based PCP programs among cancer patients and identify the multiple indicators contributing to these inequalities.
This retrospective, population-based study was a secondary data analysis of linked individual level information extracted from 6 administrative health databases and contextual (neighborhood level) data from provincial and census information. Subjects included all adults who died due to cancer between 1998 and 2003 living within 2 District Health Authorities in the province of Nova Scotia, Canada. The relationship between registration in a PCP and age was examined using hierarchical nonlinear regression modeling techniques. Identification of potential patient and ecologic contributing indicators was guided by Andersen’s conceptual model of health service utilization.
Overall, 66% of 7511 subjects were registered with a PCP. Older subjects were significantly less likely than those <65 years of age to be registered with a PCP, in particular those aged 85 years and older (adjusted odds ratio: 0.4; 95% confidence interval: 0.3–0.5). Distance to the closest cancer center had a major impact on registration.
Age continues to be a significant predictor of PCP registration in Nova Scotia even after controlling for the confounding effects of many new demographic, health service, and ecologic indicators.
PMID: 19300309 CAMSID: cams3257
aging; disparities; end-of-life care; vulnerable populations
Quality indicators (QIs) are tools designed to measure and improve quality of care. The objective of this study was to assess stakeholder acceptability of QIs of end-of-life (EOL) care that potentially were measurable from population-based administrative health databases.
After a literature review, the authors identified 19 candidate QIs that potentially were measurable through administrative databases. A modified Delphi methodology, consisting of multidisciplinary panels of cancer care health professionals in Nova Scotia and Ontario, was used to assess agreement on acceptable QIs of EOL care (n = 21 professionals; 2 panels per province). Focus group methodology was used to assess acceptability among patients with metastatic breast cancer (n = 16 patients; 2 groups per province) and bereaved family caregivers of women who had died of metastatic breast cancer (n = 8 caregivers; 1 group per province). All sessions were audiotaped, transcribed verbatim, and audited, and thematic analyses were conducted.
Through the Delphi panels, 10 QIs and 2 QI subsections were identified as acceptable indicators of quality EOL care, including those related to pain and symptom management, access to care, palliative care, and emergency room visits. When Delphi panelists did not agree, the principal reasons were patient preferences, variation in local resources, and benchmarking. In the focus groups, patients and family caregivers also highlighted the need to consider preferences and local resources when examining quality EOL care.
The findings of this study should be considered when developing quality monitoring systems. QIs will be most useful when stakeholders perceive them as measuring quality care.
PMID: 18361447 CAMSID: cams3258
end-of-life care; quality indicators; health services; quality care
Risk communication is an important component of genetic counseling. However, many authors have noted that after genetic counseling, subjective risk frequently does not match the objective risk provided by the counselor. This inevitably leads to the conclusion that the risk communication process was not “effective”. There has been much discussion about how this problem can be better addressed, such that our clients recall numeric risks more accurately after genetic counseling. This article draws on the risk and probability literature from other fields (including psychology, economics, philosophy and climate change) to deconstruct the concept of “risk” and to attempt to expand upon and develop thought and discussion about and investigation of the risk communication process in genetic counseling.
PMID: 20119700 CAMSID: cams3085
risk assessment; risk perception; risk communication; probability; clinical genetics
The ‘Barriers to Access to Care for Ethnic Minority Seniors ’ (BACEMS) study in Vancouver, British Columbia, found that immigrant families torn between changing values and the economic realities that accompany immigration cannot always provide optimal care for their elders. Ethnic minority seniors further identified language barriers, immigration status, and limited awareness of the roles of the health authority and of specific service providers as barriers to health care. The configuration and delivery of health services, and health-care providers’ limited knowledge of the seniors’ needs and confounded these problems. To explore the barriers to access, the BACEMS study relied primarily on focus group data collected from ethnic minority seniors and their families and from health and multicultural service providers. The applicability of the recently developed model of ‘candidacy’, which emphasises the dynamic, multi-dimensional and contingent character of health-care access to ethnic minority seniors, was assessed. The candidacy framework increased sensitivity to ethnic minority seniors’ issues and enabled organisation of the data into manageable conceptual units, which facilitated translation into recommendations for action, and revealed gaps that pose questions for future research. It has the potential to make Canadian research on the topic more co-ordinated.
PMID: 23814327 CAMSID: cams2473
seniors; immigrants; access to services; continuing care; British Columbia; candidacy model
Recent demonstration of the histone acetyltransferase activity of the Clock gene greatly expanded the regulatory role of circadian clocks in gene transcription. Clock and its partner Bmal1 are responsible for the generation of circadian oscillations that are synchronized (entrained) to the external light cycle. Entraining light often produces long-lasting changes in the endogenous period called aftereffects. Aftereffects are light-dependent alterations in the speed of free-running rhythms that persist for several weeks upon termination of light exposure. How light causes such long-lasting changes is unknown. However, the persistent nature of circadian aftereffects in conjunction with the long-term effects of epigenetic modifications on development and various aspects of brain physiology prompted us to hypothesize that the histone acetyltransferase CLOCK was required for circadian aftereffects. The authors exposed Clock knockout mice to 25-hour light cycles and report that these mice retain the ability to display circadian aftereffects, indicating that Clock is dispensable for this form of circadian plasticity.
PMID: 22215614 CAMSID: cams3042
aftereffects; entrainment; epigenetic; plasticity; mouse
From the individual perspective of the two authors who were long-time colleagues of Karl Lederis at the University of Calgary, the events and personal interactions are described, that are relevant to the discovery of Urotensin I (UI) in the Lederis laboratory, along with the concurrent discovery of Urotensin II (UII) in the Bern laboratory and corticotropin-releasing factor (CRF/CRH) in the Vale laboratory. The fortuitous sabbatical experiences that put Professors Lederis and Bern on the track of the Urotensins, along with the essential isolation paradigm that resulted in the complete sequencing and synthesis of UI and UII are summarized. The chance interaction between Drs. Vale and Lederis who, prior to the publications of the sequences of UI and CRF, realized the sequence commonalities of these peptides with the vasoactive frog peptide, sauvagine, is outlined. Further, the relationship between the pharmacological studies done with UI in the Calgary laboratory and the more recent understanding of the biology and receptor pharmacology for the entire Urotensin I–CRF–Urocortin peptide family is dealt with. The value of a comparative endocrinology approach to understanding hormone action is emphasized, along with a projection to the future, based on new hypotheses that can be generated by unexplained data already in the literature. Based on the previously described pharmacology of the UI–CRF–Urocortin peptides in a number of target tissues, it is suggested that the use of current molecular approaches can be integrated with a ‘classical’ pharmacological approach to generate new insights about the UI–CRF–Urocortin hormone family.
PMID: 19409389 CAMSID: cams2629
Corticotropin-releasing factor (CRF); CRF1; CRF2; Oxytocin; Urocortin; Urophysis; Urotensin; Vasopressin; Fish; Teleosts
Following proximal peripheral nerve injury, motor recovery is often poor due to prolonged muscle denervation and loss of regenerative potential. The transfer of a sensory nerve to denervated muscle results in improved functional recovery in experimental models. The authors here report the first clinical case of sensory protection. Following a total hip arthroplasty, this patient experienced a complete sciatic nerve palsy with no recovery at 3 months postsurgery and profound denervation confirmed electrodiagnostically. He underwent simultaneous neurolysis of the sciatic nerve and saphenous nerve transfers to the tibialis anterior branch of the peroneal nerve and gastrocnemius branch from the tibial nerve. He noted an early proprioceptive response. Electromyography demonstrated initially selective amelioration of denervation potentials followed by improved motor recovery in sensory protected muscles only. The patient reported clinically significant functional improvements in activities of daily living. The authors hypothesize that the presence of a sensory nerve during muscle denervation can improve functional motor recovery.
PMID: 18976091 CAMSID: cams2284
muscle denervation; sciatic nerve palsy; sensory nerve
To assess whether age-related differences in suppressing nontarget material impact subsequent performance, the authors initially asked younger and older adults to perform a go/nogo task with colored letters used as conflicting go/nogo stimuli and 2 colored numbers as low-conflict nogo stimuli. Next, participants performed another go/nogo task. A previous number was reused as a nogo stimulus and the other as a go stimulus, with new numbers serving as a baseline. In a 1st block of trials, younger adults showed slower responses to previous nogo/now-go numbers than to new go numbers, an effect not shown by older adults. Alternative accounts of these differential transfer costs are discussed.
PMID: 20718536 CAMSID: cams2238
normal aging; suppression; transfer cost; cognitive interference; go/nogo
Researchers are increasingly using observational or nonrandomized data to estimate causal treatment effects. Essential to the production of high-quality evidence is the ability to reduce or minimize the confounding that frequently occurs in observational studies. When using the potential outcome framework to define causal treatment effects, one requires the potential outcome under each possible treatment. However, only the outcome under the actual treatment received is observed, whereas the potential outcomes under the other treatments are considered missing data. Some authors have proposed that parametric regression models be used to estimate potential outcomes. In this study, we examined the use of ensemble-based methods (bagged regression trees, random forests, and boosted regression trees) to directly estimate average treatment effects by imputing potential outcomes. We used an extensive series of Monte Carlo simulations to estimate bias, variance, and mean squared error of treatment effects estimated using different ensemble methods. For comparative purposes, we compared the performance of these methods with inverse probability of treatment weighting using the propensity score when logistic regression or ensemble methods were used to estimate the propensity score. Using boosted regression trees of depth 3 or 4 to impute potential outcomes tended to result in estimates with bias equivalent to that of the best performing methods. Using an empirical case study, we compared inferences on the effect of in-hospital smoking cessation counseling on subsequent mortality in patients hospitalized with an acute myocardial infarction.
PMID: 22419832 CAMSID: cams2143
Structural variations of DNA, such as copy number variations (CNVs), are recognized to contribute both to normal genomic variability and to risk for human diseases. For example, schizophrenia has an established connection with 22q11.2 deletions. Recent genome-wide studies have provided initial evidence that CNVs at other loci may also be associated with schizophrenia. In this article, the authors provide a brief overview of CNVs, review recent findings related to schizophrenia, outline implications for clinical practice and diagnostic subtyping, and make recommendations for future reports on CNVs to improve interpretation of results.
The review included genome-wide surveys of CNVs in schizophrenia that included one or more comparison groups, were published before 2009, and used newer methods. Six studies were identified.
Despite some limitations, these initial genome-wide studies of CNVs provide replicated associations of schizophrenia with rare 1q21.1 and 15q13.3 deletions. Collectively, the results point to a more general mutational mechanism involving rare CNVs that elevate risk for schizophrenia, especially more developmental forms of the disease. Including 22q11.2 deletions, rare risk-associated CNVs appear to account for up to 2% of schizophrenia.
The more penetrant CNVs have direct implications for clinical practice and diagnostic subtyping. CNVs with lower penetrance promise to contribute to our genetic understanding of pathogenesis. The findings provide insight into a broader neuropsychiatric spectrum for schizophrenia than previously conceived and indicate new directions for genetic studies.
PMID: 20439386 CAMSID: cams2100
Histories of violence and of hyperactivity are both characterized by poor cognitive–neuropsychological function. However, researchers do not know whether these histories combine in additive or interactive ways. The authors tested 303 male young adults from a community sample whose trajectories of teacher-rated physical aggression and motoric hyperactivity from kindergarten to age 15 were well defined. No significant interaction was found. In a 1st model, both histories of problem behavior were independently associated with cognitive–neuropsychological function in most domains. In a 2nd model controlling for IQ, general memory, and test motivation, the 3 working-memory tests (relevant to executive function) remained associated with physical aggression, and 1 remained associated with hyperactivity. These results support an additive model.
PMID: 15535792 CAMSID: cams2127
Individuals with 22q11.2 deletion syndrome are known to be at high risk of developing schizophrenia. Previous imaging studies have provided limited data on the relation of schizophrenia expression in 22q11.2 deletion syndrome to specific regional brain volumetric changes. The authors hypothesized that the main structural brain finding associated with schizophrenia expression in 22q11.2 deletion syndrome, as for schizophrenia in the general population, would be gray matter volumetric deficits, especially in the temporal lobes.
MR brain images from 29 patients with 22q11.2 deletion syndrome and schizophrenia and 34 comparison subjects with 22q11.2 deletion syndrome and no history of psychosis were analyzed using a voxel-based morphometry method that also yielded volumes for related region-of-interest analyses. The authors compared data from the two groups using an analysis of covariance model correcting for total intracranial volume, age, sex, IQ, and history of congenital cardiac defects. The false discovery rate threshold was set at 0.05 to account for multiple comparisons.
Voxel-based morphometry analyses identified significant gray matter reductions in the left superior temporal gyrus (Brodmann’s area 22) in the schizophrenia group. There were no significant between-group differences in white matter or CSF volumes. Region-of-interest analyses showed significant bilateral gray matter volume reductions in the temporal lobes and superior temporal gyri in the schizophrenia group.
The structural brain expression of schizophrenia associated with the highly penetrant 22q11.2 deletion involves lower gray matter volumes in temporal lobe regions. These structural MRI findings in a 22q11.2 deletion syndrome form of schizophrenia are consistent with those from studies involving schizophrenia samples from the general population. The results provide further support for 22q11.2 deletion syndrome as a genetic subtype and as a useful neurodevelopmental model of schizophrenia.
PMID: 21362743 CAMSID: cams2144
In this systematic review we evaluated the effectiveness of emergency department (ED)-based management interventions for mental health presentations with an aim to provide recommendations for pediatric care.
A search of electronic databases, references, key journals and conference proceedings was conducted and primary authors contacted. Experimental and observational studies that evaluated ED crisis care with pediatric and adult patients were included. Adult-based studies were evaluated for potential translation to pediatric investigation. Pharmacological-based studies were excluded. Inclusion screening, study selection, and methodological quality were assessed by two independent reviewers. One reviewer extracted the data and a second checked for completeness and accuracy. Presentation of study outcomes included odds ratios (OR) and mean differences (MD) with 95% confidence intervals (CI). Meta-analysis was deferred due to clinical heterogeneity in intervention, patient population, and outcome.
Twelve observational studies were included in the review with pediatric (n=3), and adult or unknown (n=9) aged participants. Pediatric studies supported the use of specialized care models to reduce hospitalization (OR=0.45; 95%CI:0.33,0.60), return ED visits (OR=0.60, 95%CI:0.28,1.25), and length of ED stay (MD=−43.1min; 95%CI:−63.088,−23.11). In an adult study, reduced hospitalization was reported in a comparison of a crisis intervention team to standard care (OR=0.59; 95%CI:0.43,0.82). Five adult-based studies assessed triage scales; however, little overlap in the scales investigated and the outcomes measured limited comparability and generalizability for pediatrics. In a comparison of a mental health scale to a national standard, one study demonstrated reduced ED wait (MD=−7.7 min; 95%CI:−12.82,−2.58) and transit (MD=−17.5 min; 95%CI:−33.00,−1.20) times. Several studies reported a shift in triage scores of psychiatric patients dependent on the scale or nurse training (psychiatric vs. emergency), but linkage to system- or patient-based outcomes was not made limiting clinical interpretation.
Pediatric studies have demonstrated that the use of specialized care models for mental health care can reduce hospitalization, return ED visits, and length of ED stay. Evaluation of these models using more rigorous study designs and the inclusion of patient-based outcomes will improve this evidence base. Adult-based studies provided recommendations for pediatric research including a focus on triage and restraint use.
PMID: 21131813 CAMSID: cams1631
mental health services; crisis; emergency care
Both depression and smoking are highly prevalent and related to poorer outcomes in cardiac patients. In this study, the authors examined the association between depressive symptoms and smoking status, described the frequency and type of antidepressant use, and prospectively tested the effects of antidepressant use in smokers on smoking status and psychosocial outcomes. Participants comprised 1498 coronary artery disease (CAD) outpatients who completed a baseline survey which assessed depressive symptoms, current medications, and smoking status. A second survey was mailed 9 months later that assessed depressive symptoms, anxiety, insomnia, current medications and smoking status. Results showed that current and former-smokers had significantly greater depressive symptoms than non-smokers. Ten percent of patients were taking antidepressants, most frequently SSRIs, with significantly more smokers on antidepressants than former and non-smokers. At follow-up, smokers on antidepressants were less likely to have quit, had greater anxiety, depressive symptoms and insomnia than smokers not using antidepressants. This study demonstrated that smokers and quitters with CAD had greater depressive symptoms and use of antidepressants than non-smokers, but that the antidepressants utilized may not be optimizing outcomes.
PMID: 19504177 CAMSID: cams1434
Smoking; Depression; Antidepressants; Coronary artery disease (CAD); Outpatients
This systematic review evaluated the effectiveness of professional and organizational interventions aimed at improving medical processes, such as documentation or clinical assessments by health care providers, in the care of pediatric emergency department (ED) patients where abuse was suspected.
A search of electronic databases, references, key journals/conference proceedings was conducted and primary authors contacted. Studies whose purpose was to evaluate a strategy aimed at improving ED clinical care of suspected abuse were included. Study methodological quality was assessed by two independent reviewers. One reviewer extracted the data and a second checked for completeness and accuracy.
Six studies met the inclusion criteria: one randomized (RCT) and one quasi-randomized trial (qRCT), and four observational studies. Study quality ranged from modest (observational studies) to good (trials). Variation in study interventions and outcomes limited between study comparisons. One qRCT supported self-instructional education kits as a means to improve physician knowledge for both physical abuse (mean pre-test score: 13.12, SD 2.36; mean post-test score: 18.16, SD 1.64) and sexual abuse (mean pre-test score: 10.81, SD 3.20; mean post-test score: 18.45, SD 1.79). Modest quality observational studies evaluated reminder systems for physician documentation with similar results across studies. Compared to standard practice, chart checklists paired with an educational program increased physician consideration of non-accidental burns in burn cases (59% increase), documentation of time of injury (36% increase), as well as documentation of consistency (53% increase) and compatibility (55% increase) of reported histories. Decisional flowcharts for suspected physical abuse also increased documentation of non-accidental physical injury (69.5% increase; p<0.0001) and had a similar significant impact as checklists on increasing documentation of history consistency and compatibility (69.5% and 70.0% increases, respectively; p<0.0001) when compared to standard practice. No improvements were noted in these studies for documentation of consultations or current status with child protective services. The introduction of a specialized team and crisis center to standardize practice had little effect on physician documentation, but did increase documentation of child protective services involvement (22.7% increase; p<0.005) and discharge status (23.7% increase; p<0.02). Referral to social services increased in one study following the introduction of a chart checklist (8.6% increase; p=0.018). A recently conducted multi-site RCT did not support observational findings, reporting no significant effect of educational sessions and/or a chart checklist on ED practices.
The small number of studies identified in this review highlights the need for future studies that address care of a vulnerable clinical population. While moderate quality observational studies suggested education and reminder systems increased clinical knowledge and documentation, these findings were not supported by a single randomized trial. The limited theoretical base for conceptualizing change in health care providers and the influence of the ED environment on clinical practice are limitations to this current evidence base.
PMID: 20370740 CAMSID: cams1630
The lamin B2 locus is the only mammalian origin whose replication initiation points (RIPs) have been mapped. Although this paper was published 8 years ago, no further mammalian RIP-mapping studies have been reported, largely due to technical difficulties of ligation-mediated (LM)-PCR used by the authors. Here, we report the development of a simple, one-way PCR-based protocol that allows one to accurately determine RIPs at mammalian origins. The procedure can be completed within 48 h from the time of cell lysis in the agarose gel. Nascent DNA is then isolated from the same gel after DNA is separated by alkaline gel electrophoresis. Subsequently, RIPs are determined by one-way PCR-based primer extension using labeled primers. Using this protocol, we have successfully mapped RIPs in the human DBF4 locus. As one-way PCR is routinely used by many scientists, this protocol will provide a powerful new tool for studying DNA replication in many organisms including mammalian cells.
PMID: 18927558 CAMSID: cams351
The authors examined whether the supply of primary care physicians had protective effects on breast cancer stage and survival in Ontario and whether supply losses during the 1990s were associated with diminished protection.
Random samples of the Ontario Cancer Registry, respectively, provided 879 women and 951 women who were diagnosed with breast cancer between 1988 and 1990 (followed until 1996) and 1998 and 2000 (followed until 2006), respectively. Active physician supply data (1991 and 2001) joined to each woman’s census division of residence was taken from the Scott’s Medical Database.
Protective thresholds were observed among the earlier cohort for supplies of general practitioners (7 per 10,000 population) and supplies of obstetricians/gynecologists (6 per 100,000 population) at or above which women with breast cancer were significantly more likely to have been diagnosed with localized disease and to have survived for ≥5 years. These protective effects seemed generally attenuated among the more recent cohort. The risk of living in primary care physician-undersupplied areas increased significantly between 1991 and 2001 (10%–30%), and such physician supply losses were associated with reduced cancer care protection, including less prevalent early diagnoses (odds ratio [OR], 1.60; 95% confidence interval [95% CI], 1.00–2.58) and lower 5-year survival rates (OR, 1.62; 95% CI, 1.03–2.55).
Primary care physician supplies appeared to matter very much in the effective provision of cancer care in Canada. Community healthcare service endowments that include adequate physician supplies may be particularly critical to the performance of a healthcare system such as that in Canada, which provides universal accessibility to medically necessary care.
PMID: 19484796 CAMSID: cams1397
physician supplies; primary care; general practitioners; family physicians; obstetrician/gynecologists; healthcare service endowments; breast cancer; stage at diagnosis; survival; Ontario; Canada
The authors identified a missense mutation in the FTL gene (474G>A; A96T) in a 19-year-old man with parkinsonism, ataxia, corticospinal signs, mild nonprogressive cognitive deficit, and episodic psychosis. This mutation was also present in his asymptomatic mother and younger brother, who had abnormally low levels of ferritin in the serum. The patient and his mother displayed bilateral involvement of the pallidum.
PMID: 16116125 CAMSID: cams1060
Reproduction is at the core of many aspects of human existence. It is intrinsic in our biology and in the broad social constructs in which we all reside. The introduction to this special issue is designed to reflect on some of the differences between the humanities/arts and the sciences on the subject of Reproduction now and in the past. The intellectual/cultural distance between humanists and reproductive biologists is vast, yet communication between the Two Cultures has much to offer in guiding future research, pedagogy, and social policy. The challenges to communication include differences in methodology, professional protocols, specialization, and the increasing speed with which reproductive technology advances. The solutions require a new kind of student who can learn and adapt the approaches from both sides of the disciplinary divide to create new ways of understanding how our current and future concepts of reproduction may be informed by the past. This co-authored introduction reviews the range of interests represented in the essays and represents first steps of a dialogue between a humanist and a reproductive biologist who chart some of the possibilities on what the future of the subject might hold.
PMID: 19937463 CAMSID: cams562
Reproduction; Humanities; Science; History; Imaging; Transdisciplinarity
Age-associated telomere shortening leads to replicative senescence of human endothelial cells (EC). Risk factors for cardiovascular disease (CVD) accelerate ageing, while there is a concomitant rise in oxidative stress known to promote stress-induced senescence (SIS) in vitro. Of all risk factors for CVD, smoking is most associated with the development of inflammation and accelerated atherosclerosis due to a prooxidant–antioxidant imbalance. We tested the hypothesis that SIS predominates in EC isolated from chronic smokers with premature atherosclerosis undergoing coronary artery bypass graft surgery (CABG). We isolated and cultured EC from segments of internal mammary arteries from smoker, former smoker, and nonsmoker coronary patients. Senescence of EC was induced by serial passage and quantified by the measurement of telomere length and senescence-associated β-galactosidase activity. Compared with nonsmokers, smoker patients were 10 years younger at the time of CABG, evidence of premature atherosclerosis. Cellular senescence was independent of telomere length and directly related to oxidative damage. EC exhibited higher expression levels of markers of oxidative stress (lipid peroxydation level and caveolin-1 mRNA), inflammation (angiopoietin-like 2 mRNA), hypoxia (vascular endothelial growth factor (VEGF)-A mRNA), and cell damage (p53 mRNA). In conclusion, a high oxidative stress environment in EC isolated from atherosclerotic chronic smokers predisposes to SIS rather than replicative senescence.
PMID: 19011671 CAMSID: cams3025
smoking; atherosclerosis; oxidative stress; caveolin-1; stress-induced senescence; telomere; replicative senescence