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1.  Uncertainty and perception of danger among patients undergoing treatment for prostate cancer 
BJU international  2012;111(3 0 0):E84-E91.
To investigate patient uncertainty and perception of danger regarding prospects for clinical prostate cancer control.
To determine the impact of these factors on satisfaction with overall prostate cancer treatment outcome.
Men who had undergone primary treatment for early stage prostate cancer and who were participants in the Prostate Cancer Outcomes and Satisfaction with Treatment Quality Assessment (PROSTQA) prospective cohort study of prostate cancer outcomes (the parent study) were offered the opportunity to participate in the present study.
Centralized phone interviews were conducted to determine patient-reported uncertainty regarding cancer status (measured by the Mishel Uncertainty in Illness Scale-Community Form), perception of danger (measured by Folkman and Lazarus’ Appraisal Scale) and satisfaction with treatment outcome (measured by the Service Satisfaction Scale for Cancer Care). The study used the same centralized telephone interview centre as was used in the parent study.
Data were collected at 48, 60 or 72 months after the completion of prostate cancer treatment.
Relationships among measures were characterized by Spearman rank correlation coefficients (r).
A total of 338 agreed to participate, representing 76% of those who were invited.
Younger patients experienced less uncertainty (r = 0.20, P < 0.001), yet reported greater perception of danger (r = −0.12; P = 0.03) concerning their previously treated prostate cancer.
African-American patients showed greater uncertainty than other ethnic groups (P = 0.005) but did not have a greater perception of danger (P = 0.36).
Education played a major role in uncertainty; patients with lower levels of education tended to report higher degrees of uncertainty (r = −0.25; P < 0.001).
There was a mild to moderate general association between the three outcomes. A greater sense of uncertainty was associated with a greater perception of danger (r = 0.34, P < 0.001), and as danger and uncertainty increased, satisfaction with treatment outcome tended to decrease (r was between −0.30 and −0.34, P < 0.001).
Results suggest that possible disparities related to patient racial background and education may exist in the perception of cancer-related uncertainty.
Racial and educational disparities, coupled with a mild to moderate association of uncertainty or danger perception and overall outcome satisfaction, suggest an unmet need for healthcare and nursing services for men undergoing treatment for prostate cancer.
PMCID: PMC4075327  PMID: 22985348
2.  Respiratory treatment history predicts suck pattern stability in preterm infants 
Journal of neonatal nursing : JNN  2008;14(6):185-192.
Sensory deprivation and motor restriction associated with extensive oxygen therapy may lead to poor oromotor control in preterm infants. Non-nutritive suck is one of the first complex oromotor behaviors infants perform. This study determined the spatiotemporal variability of non-nutritive suck (NNS) pressure trajectories in three preterm groups with differing oxygen histories—one control group with minimal or no O2 therapy, and two Respiratory Distress Syndrome (RDS) groups with either a mild/moderate (RDS1) or moderate/severe (RDS2) O2 history. The Non-nutritive Suck Spatiotemporal Index (NNS STI) quantifies spatial and temporal variability across kinematic trajectories, and was calculated from digital representations of infants’ suck pressure signals. An ANCOVA revealed a significant effect for group (p < .001) on the NNS STI measure, with RDS2 infants showing highly variable NNS patterning, and thus relatively underdeveloped suck. Extensive oxygen therapy, which alters the oral sensory environment and reduces motor experiences, disrupts the development of coordinated NNS in preterm infants.
PMCID: PMC2614286  PMID: 19956344
Premature infant; Respiratory Distress Syndrome; Non-nutritive suck; Oromotor control; Spatiotemporal index; Suck variability; Suck central pattern generator; Oxygen therapy; Motor function
Nature medicine  2009;15(8):951-954.
Neutralizing antibodies are thought crucial to HIV vaccine protection but a major hurdle is the high antibody concentrations likely required as suggested by studies in animal models1. However, these studies typically apply a large virus inoculum to ensure infection in control animals in single challenge experiments. In contrast, most human infection via sexual encounter probably involves repeated exposures to much lower doses of virus2–4. Therefore, animal studies may have overestimated protective antibody levels in humans. To investigate the impact of virus challenge dose on antibody protection, we repeatedly exposed macaques intravaginally to low doses of a CCR5 coreceptor-using SHIV (an HIV/SIV chimera) in the presence of antibody at plasma concentrations leading to relatively modest neutralization titers of the order of 1:5 IC90 values in a PBMC assay. An effector function deficient variant of the neutralizing antibody was also included. The results show that a significantly greater number of challenges are required to infect animals treated with neutralizing antibody than control antibody-treated animals, and the notion that effector function may contribute to antibody protection is supported. Overall, the results imply that lower levels of antibody than considered hereto may provide benefit in the context of typical human exposure to HIV-1.
PMCID: PMC4334439  PMID: 19525965
5.  Assessing the experiences of intra-uterine device users in a long-term conflict setting: a qualitative study on the Thailand-Burma border 
Conflict and Health  2015;9(1):6.
In Burma, severe human rights violations, civil conflict, and the persecution of ethnic and linguistic minority populations has resulted in the displacement of millions of people, many of whom now reside as internally displaced populations (IDPs) in Eastern Burma or in Thailand as refugees or undocumented migrants. Use of the intra-uterine device (IUD), a non-user dependent and highly reliable method of long acting reversible contraception, has the potential to make a significant impact on reproductive health in this protracted conflict setting.
This qualitative study aimed to understand Burmese women’s experiences with and perceptions of the IUD and identify avenues for improving contraceptive service delivery along the Thailand-Burma border.
In the summer of 2013, we conducted in-person in-depth open-ended interviews with 31 women who obtained IUDs from a clinic along the border. We conducted a content and thematic analysis of these data using both a priori (pre-determined) and emergent codes and inductive techniques.
Women’s experiences with the IUD are overwhelmingly positive and the experiences of friends and family impact use of the device. Financial considerations and access to reproductive health facilities also shape the use of the IUD in this region. The IUD is rare along the Thailand-Burma border and misinformation about this method of contraception is pervasive.
Our findings suggest that this modality of contraception is culturally acceptable and may be able to address structural barriers to reproductive health services along the Thailand-Burma border. Ensuring that information provided by health care providers and among peer groups is evidence-based, a full range of contraceptive methods is available, and adoption of an IUD is affordable are priorities for expanding access to reproductive health services in this setting.
PMCID: PMC4330595
Myanmar; Contraception; Family planning; Abortion; Maternal health; Refugees
6.  College Student Beliefs About Wagering: An Evaluation of the Adolescent Gambling Expectancies Survey 
Expectancy theory posits that decisions to engage in a given behavior are closely tied to expectations of the outcome of that behavior. Gambling outcome expectancies have predicted adolescent gambling and gambling problems. When high school students’ outcome expectancies were measured by Wickwire, Whelan and Meyers (2010), the Adolescent Gambling Expectancy Survey (AGES) revealed five categories of expectancies that were each predictive of gambling frequency and pathology. The present study aimed to explore if the AGES could be successfully replicated with college students. When administered to a diverse college student population, factor analyses identified five factors similar to those found in the high school sample. Several factors of the AGES were also found to predict gambling frequency and gambling problems for college students. Gambling frequency and gambling activity preference were also addressed.
PMCID: PMC3921269  PMID: 23934368
college student gambling; outcome expectancies
7.  Data Standards ≠ Data Quality 
The relationship between data quality and data standards has not been clearly articulated. While some directly state that data standards increase data quality, others claim the opposite. Depending on the type of data standard and the aspects of data quality considered, both arguments may in fact be correct. We deconstruct a typology of data standards and apply a dimensional definition of data quality to clearly articulate the relationship between the two, providing a framework for data quality planning.
PMCID: PMC4317361  PMID: 23920982
Data standards; data quality; information quality; Clinical informatics; Clinical research informatics
8.  Population Structure of KPC-Producing Klebsiella pneumoniae Isolates from Midwestern U.S. Hospitals 
Genome sequencing of carbapenem-resistant Klebsiella pneumoniae isolates from regional U.S. hospitals was used to characterize strain diversity and the blaKPC genetic context. A phylogeny based on core single-nucleotide variants (SNVs) supports a division of sequence type 258 (ST258) into two distinct groups. The primary differences between the groups are in the capsular polysaccharide locus (cps) and their plasmid contents. A strict association between clade and KPC variant was found. The blaKPC gene was found on variants of two plasmid backbones. This study indicates that highly similar K. pneumoniae subpopulations coexist within the same hospitals over time.
PMCID: PMC4136011  PMID: 24913165
9.  Robotic assisted Ivor Lewis esophagectomy in the elderly patient 
Robotic assisted approaches to esophagectomy have demonstrated decreased complications and length of hospitalization. We sought to examine the impact of age on outcomes in patients undergoing robotic assisted Ivor Lewis esophagectomy (RAIL).
A retrospective review of all patients undergoing RAIL from 2009-2013 was conducted. Statistical analysis was performed for the entire cohort and by stratifying patients into three age cohorts: ≤49, 50-69, ≥70.
We identified 134 patients and found no statistically significant difference for operative time, length of hospitalization, adverse events (AE), or mortality. There was a higher median blood loss (150 cc) seen in cohorts 1 (50-600 cc) and 3 (50-400 cc) compared to cohort 2 [100 (range, 25-400) cc; P<0.01]. The overall AE rate was 10% (cohort 1), 22% (cohort 2), 35% (cohort 3), P=0.13. There were 5 (4%) leaks and 2 (1.5%) deaths, but this was not significantly different between cohorts (P=0.40, P=0.91, respectively).
RAIL is a safe surgical technique for use in an aging patient population. There was no increased risk of AE or death in the elderly patients compared to younger patients undergoing the robotic approach.
PMCID: PMC4294822  PMID: 25642335
Esophageal cancer; elderly; robotic esophageal
10.  Concurrent chemoradiotherapy with protracted infusion of 5-fluorouracil (5-FU) and cisplatin for locally advanced resectable esophageal cancer 
Neoadjuvant concurrent chemoradiotherapy (CCRT) has become the standard treatment for esophageal cancer (EC) in North America. The cisplatin/5-flurouracil (5-FU) combination has been the most commonly used regimen. For the last 15 years we incorporated a daily continuous infusion of 5-FU and 2 doses of cisplatin into our neoadjuvant CCRT for potentially resectable EC.
Patients and methods
Between July 1997 and June 2012, 129 patients with locally advanced EC (T3 or N1 and higher), received neoadjuvant CCRT with cisplatin 75 mg/m2 on day 1 and day 29 and continuous infusion of 5-FU (225 mg/m2/day) on the days of radiation.
The median age of patients was 63 years, 85% had adenocarcinoma, 29, 74 and 26 patients had stage II, III and IVa disease respectively, 110 patients had N1 disease based on the American Joint Committee on Cancer (AJCC) 6th edition, 118 patients experienced weight loss during treatment. All patients completed treatment. Treatment was well tolerated with 14% of patients having ≥ grade 3 toxicity and 18 patients requiring hospital admission. Sixty-four percent of patients had surgical resection following CCRT, with disease progression and patient refusal being the most common reasons for not proceeding with surgery. An R0 resection was achieved in 96% of patients. A pathological complete response (pCR) was achieved in 45% of patients. With a median follow up of 26 months (1.2-144 months), 48/129 patients recurred and 60/129 died of their disease.
Our study has its limitation, however, and compared to the conventional chemotherapy regimens containing the cisplatin/5-FU doublet, our treatment strategy for locally advanced EC CCRT seems to be feasible and well tolerated.
PMCID: PMC4294830  PMID: 25642336
5-fluorouracil (5-FU); cisplatin; esophageal cancer (EC)
12.  Do Australian general practitioners believe practice nurses can take a role in chlamydia testing? A qualitative study of attitudes and opinions 
Chlamydia notifications continue to rise in young people in many countries and regular chlamydia testing is an important prevention strategy. Although there have been initiatives to increase testing in primary care, none have specifically investigated the role of practice nurses (PNs) in maximising testing rates. PNs have previously expressed a willingness to be involved, but noted lack of support from general practitioners (GPs) as a barrier. We sought GPs’ attitudes and opinions on PNs taking an expanded role in chlamydia testing and partner notification.
In the context of a cluster randomised trial in mostly rural towns in 4 Australian states, semi structured interviews were conducted with 44 GPs between March 2011 and July 2012. Data relating to PN involvement in chlamydia testing were thematically analysed using a conventional content analysis approach.
The majority of GPs interviewed felt that a role for PNs in chlamydia testing was appropriate. GPs felt that PNs had more time for patient education and advice, that patients would find PNs easier to talk to and less intimidating than GPs, and that GPs themselves could benefit through a reduction in their workload. Although GPs felt that PNs could be utilised more effectively for preventative health activities such as chlamydia testing, many raised concerns about how these activities would be renumerated whilst some felt that existing workload pressures for PNs could make it difficult for them to expand their role. Whilst some rural GPs recognised that PNs might be well placed to conduct partner notification, they also recognised that issues of patient privacy and confidentiality related to living in a “small town” was also a concern.
This is the first qualitative study to explore GPs’ views around an increased role for PNs in chlamydia testing. Despite the concerns raised by PNs, these findings suggest that GPs support the concept and recognise that PNs are suited to the role. However issues raised, such as funding and remuneration may act as barriers that will need to be addressed before PNs are supported to make a contribution to increasing chlamydia testing rates in general practice.
PMCID: PMC4314754
13.  Why are we not screening for anal cancer routinely - HIV physicians’ perspectives on anal cancer and its screening in HIV-positive men who have sex with men: a qualitative study 
BMC Public Health  2015;15:67.
Anal cancer is a priority health issue in HIV positive men who have sex with men. Anal cancer screening may be aimed at either detecting the precursor lesion (high grade anal intraepithelial neoplasia(HGAIN)) or early anal cancer. To date no qualitative study has explored the views of HIV physicians regarding anal cancer and its screening.
We conducted indepth interviews with 20 HIV physicians (Infectious diseases, Immunology, Sexual health, General practice) in different settings (hospital, sexual health centres, general practice) from around Australia. Framework analysis was used to identify themes.
HIV physicians viewed anal cancer as a significant health issue and all agreed on the importance of anal cancer screening amongst HIV positive MSM if a valid screening method was available. Barriers for utilizing anal cytology was based primarily on the theme of insufficient evidence (e.g. no studies demonstrating reduction in mortality following screening or effective treatments for HGAIN). Barriers for utilizing DARE for early cancer detection were based on systemic factors (e.g. lack of opportunity, lack of priority, differences in HIV care practices); health provider factors (lack of evidence, difficulty discussing with patients, lack of confidence in DARE) and patient factors (perceived discomfort of DARE for patients, low anal cancer risk awareness). Physicians were willing to consider the idea of patient self-examination and partner-examination although concerns were raised regarding its reliability and issues surrounding partner dynamics.
HIV physicians remain ambivalent regarding the most effective means to screen for anal cancer. More research is needed to address the physicians’ concerns before anal cancer screening can be implemented into routine HIV care.
PMCID: PMC4314790  PMID: 25636181
Anal cancer; Screening; HIV; Men who have sex with men
14.  Mineralocorticoid Receptors Modulate Vascular Endothelial Function in Human Obesity 
Obesity increases linearly with age and is associated with impaired vascular endothelial function and increased risk for cardiovascular disease. Mineralocorticoid receptors (MR) contribute to impaired vascular endothelial function in cardiovascular disease; however, their role in uncomplicated human obesity is unknown. Because plasma aldosterone levels are elevated in obesity and adipocytes may be a source of aldosterone, we hypothesized that MR modulate vascular endothelial function in older adults in an adiposity-dependent manner. To test this hypothesis, we administered MR blockade (Eplerenone; 100 mg/day) for 1 month in a balanced, randomized, double-blind, placebo-controlled, crossover study to 22 older adults (10 men, 55–79 years) varying widely in adiposity (body mass index: 20–45 kg/m2) but who were free from overt cardiovascular disease. We evaluated vascular endothelial function (brachial artery flow-mediated dilation [FMD] via ultrasonography) and oxidative stress (plasma F2-isoprostanes and vascular endothelial cell protein expression of nitrotyrosine and NADPH oxidase p47phox) during placebo and MR blockade. In the whole group, oxidative stress (P>0.05) and FMD did not change with MR blockade (6.39±0.67 vs. 6.23±0.73 %, P=0.7, placebo vs. Eplerenone). However, individual improvements in FMD in response to Eplerenone were associated with higher total body fat (body mass index: r=0.45, P=0.02 and DXA-derived % body fat: r=0.50, P=0.009) and abdominal fat (total: r=0.61, P=0.005, visceral: r=0.67, P=0.002 and subcutaneous: r=0.48, P=0.03). In addition, greater improvements in FMD with Eplerenone were related with higher baseline fasting glucose (r=0.53, P=0.01). MR influence vascular endothelial function in an adiposity-dependent manner in healthy older adults.
PMCID: PMC4312011  PMID: 23786536
brachial artery; flow-mediated dilation; abdominal visceral and subcutaneous fat
15.  A genome-wide association study of marginal zone lymphoma shows association to the HLA region 
Vijai, Joseph | Wang, Zhaoming | Berndt, Sonja I. | Skibola, Christine F. | Slager, Susan L. | de Sanjose, Silvia | Melbye, Mads | Glimelius, Bengt | Bracci, Paige M. | Conde, Lucia | Birmann, Brenda M. | Wang, Sophia S. | Brooks-Wilson, Angela R. | Lan, Qing | de Bakker, Paul I. W. | Vermeulen, Roel C. H. | Portlock, Carol | Ansell, Stephen M. | Link, Brian K. | Riby, Jacques | North, Kari E. | Gu, Jian | Hjalgrim, Henrik | Cozen, Wendy | Becker, Nikolaus | Teras, Lauren R. | Spinelli, John J. | Turner, Jenny | Zhang, Yawei | Purdue, Mark P. | Giles, Graham G. | Kelly, Rachel S. | Zeleniuch-Jacquotte, Anne | Ennas, Maria Grazia | Monnereau, Alain | Bertrand, Kimberly A. | Albanes, Demetrius | Lightfoot, Tracy | Yeager, Meredith | Chung, Charles C. | Burdett, Laurie | Hutchinson, Amy | Lawrence, Charles | Montalvan, Rebecca | Liang, Liming | Huang, Jinyan | Ma, Baoshan | Villano, Danylo J. | Maria, Ann | Corines, Marina | Thomas, Tinu | Novak, Anne J. | Dogan, Ahmet | Liebow, Mark | Thompson, Carrie A. | Witzig, Thomas E. | Habermann, Thomas M. | Weiner, George J. | Smith, Martyn T. | Holly, Elizabeth A. | Jackson, Rebecca D. | Tinker, Lesley F. | Ye, Yuanqing | Adami, Hans-Olov | Smedby, Karin E. | De Roos, Anneclaire J. | Hartge, Patricia | Morton, Lindsay M. | Severson, Richard K. | Benavente, Yolanda | Boffetta, Paolo | Brennan, Paul | Foretova, Lenka | Maynadie, Marc | McKay, James | Staines, Anthony | Diver, W. Ryan | Vajdic, Claire M. | Armstrong, Bruce K. | Kricker, Anne | Zheng, Tongzhang | Holford, Theodore R. | Severi, Gianluca | Vineis, Paolo | Ferri, Giovanni M. | Ricco, Rosalia | Miligi, Lucia | Clavel, Jacqueline | Giovannucci, Edward | Kraft, Peter | Virtamo, Jarmo | Smith, Alex | Kane, Eleanor | Roman, Eve | Chiu, Brian C. H. | Fraumeni, Joseph F. | Wu, Xifeng | Cerhan, James R. | Offit, Kenneth | Chanock, Stephen J. | Rothman, Nathaniel | Nieters, Alexandra
Nature Communications  2015;6:5751.
Marginal zone lymphoma (MZL) is the third most common subtype of B-cell non-Hodgkin lymphoma. Here we perform a two-stage GWAS of 1,281 MZL cases and 7,127 controls of European ancestry and identify two independent loci near BTNL2 (rs9461741, P=3.95 × 10−15) and HLA-B (rs2922994, P=2.43 × 10−9) in the HLA region significantly associated with MZL risk. This is the first evidence that genetic variation in the major histocompatibility complex influences MZL susceptibility.
Marginal zone lymphoma (MZL) is a common subtype of B-cell non-Hodgkin lymphoma. Here the authors carry out a two-stage genome-wide association study in over 8,000 Europeans and identify two new MZL risk loci at chromosome 6p, implicating the major histocompatibility complex in the disease for the first time.
PMCID: PMC4287989  PMID: 25569183
16.  Motivations for Providing a Secure Base: Links with Attachment Orientation and Secure Base Support Behavior 
Attachment & human development  2013;15(3):261-280.
This investigation examined the importance of underlying motivations in predicting secure base support behavior, as well as the extent to which support motivations are predicted by individual differences in attachment orientation. Participants were 189 married couples who participated in two laboratory sessions: During a questionnaire session, couples completed assessments of their underlying motivations for providing, and for not providing, support for their partner's exploration (i.e., goal-strivings), as well as assessments of their typical secure base support behavior. In an observational session, couples engaged in a discussion of one member's personal goals, during which the partner's secure base support was assessed. Results revealed a variety of distinct motivations for providing, and for not providing, secure base support to one's partner, as well as theoretically expected links between these motivations and both secure base behavior and attachment orientation. This work establishes motivations as important mechanisms that underlie the effective or ineffective provision of relational support.
PMCID: PMC4308721  PMID: 23581972
motivations; secure base; caregiving; social support; attachment; exploration; goals
17.  Transmembrane fragment structures of Amyloid Precursor Protein depend on membrane surface curvature 
The amyloid β (Aβ) peptide associated with Alzheimer’s Disease results from processing of the amyloid precursor protein (APP) by secretases. Following cleavage of APP by β-secretase, a 99 amino acid C-terminal fragment of APP (C99) is produced consisting of a single transmembrane (TM) helix. Simulation studies of C99 congeners and structural studies of C99 in surfactant micelles and lipid vesicles have shown that a key peptide structural motif is a prominent “GG kink,” centered at two glycines and dividing the TM helix. The flexibility of the GG kink is important in the processing of C99 by γ-secretase. We performed multiscale simulations of C9915–55 in a DPC surfactant micelle and POPC lipid bilayer in order to elucidate the role of membrane surface curvature in modulating the peptide structure. C9915–55 in a DPC surfactant micelle possesses a “GG kink” in the TM domain near the dynamic hinge located at G37/G38, while such a kink is not observed in C9915–55 in a POPC lipid bilayer. Intramolecular interaction between the extracellular and TM domains of C9915–55 is enhanced in the micelle environment, influencing helical stability, TM helix extension, exposure to water, and depth of insertion in the lipophilic region. Our results point to critical differences in C9915–55 structures in micelle and bilayer environments, and show that the fluctuations of the structural ensemble of APP are strongly influenced by membrane surface curvature.
PMCID: PMC3928069  PMID: 24364734
19.  Organized Labor and Racial Wage Inequality in the United States1  
AJS; American journal of sociology  2012;117(5):1460-1502.
Why have African-American private-sector unionization rates surpassed those of white workers for decades, and how has private-sector union decline exacerbated black-white wage inequality? Using data from the Current Population Survey (1973–2007), the authors show that African-Americans join unions for protection against discriminatory treatment in nonunion sectors. A model-predicted wage series also shows that, among women, black-white weekly wage gaps would be between 13% and 30% lower if union representation remained at high levels. The effect of deunionization on racial wage inequality for men is less substantial, but without deunionization, weekly wages for black men would be an estimated $49 higher. The results recast organized labor as an institution vital for its economic inclusion of African-American men and women. This study points to the need to move beyond class-based analyses of union decline to an understanding of the gendered role unions once played in mitigating racial inequality.
PMCID: PMC4300995  PMID: 25620802
20.  The Hybrid Lid Crease Approach to Address Lateral Frontal Sinus Disease With Orbital Extension 
This study aimed to describe the hybrid lid crease approach in conjunction with functional endoscopic sinus surgery (FESS) for lateral frontal sinus disease with orbital extension.
Study Design
Retrospective case review.
Patients undergoing hybrid lid crease approach with FESS for frontal sinus disease were reviewed retrospectively. Surgical indications consisted of inverting papilloma with extension into the frontal sinus (n = 1) and frontal sinus mucocele (n = 2). Inclusion criteria included presence of disease in the lateral frontal sinus with extension into the orbital space and erosion of the superior orbital rim. Preoperative and postoperative parameters included complete ophthalmologic exam, endoscopic exam, and computed tomography scan.
We were able to access the frontal sinus and orbit in all 3 cases and address sinus pathology of the lateral frontal sinus and orbit using the lid crease approach with FESS. All patients had improvement in ophthalmologic symptoms and interval disease resolution and were satisfied with their postoperative lid crease incision.
The lid crease approach offers direct access to the frontal sinus with minimal dissection through a well-hidden incision. In our case series of lateral frontal sinus pathology with orbital extension, the hybrid lid crease approach with FESS allowed complete eradication of disease without recurrence.
PMCID: PMC4301847  PMID: 24944279
frontal sinus; endoscopic; lid crease; inverted papilloma; mucocele
21.  Changes in malaria epidemiology in a rural area of Cubal, Angola 
Malaria Journal  2015;14:21.
Scarce information about malaria epidemiology in Angola has been published. The objective of this study is to describe the epidemiology of malaria at the Hospital Nossa Senhora da Paz (Cubal, Angola) and the fatality rate due to malaria (total and in children under five years) in the last five years.
A retrospective, observational study was performed at the Hospital Nossa Senhora da Paz, a 400-bed rural hospital located in Benguela Province of Angola. The study population included all patients who attended the hospital from January 2009 to December 2013. Outcome variables were calculated as follows: the percentage of malaria cases (number of positive thick blood films, divided by the total thick blood films performed); the percentage of in-patients for malaria (number of in-patients diagnosed with malaria, divided by the total number of in-patients); and, the fatality rate (number of deaths due to malaria divided by the number of positive thick blood films).
Overall, 23,106 thick blood films were performed, of which 3,279 (14.2%) were positive for Plasmodium falciparum infection. During this five-year period, a reduction of 40% (95% CI 37-43%, p < 0.001) in the malaria-positive slides was detected. Distribution of positive-malaria slides showed a seasonal distribution with a peak from December to March (rainy season). An average annual reduction of 52% (95% CI 50-54%, p < 0.001) in the admissions due to malaria was observed. The overall fatality rate due to malaria was 8.3%, and no significant differences in the annual fatality rate were found (p = 0.553).
A reduction in the number of malaria cases and the number of admissions due to malaria has been observed at the Hospital Nossa Senhora da Paz, during the last five years, and incidence along the study period showed a seasonal distribution. All this information could be useful when deciding which malaria control strategies have to be implemented in this area.
PMCID: PMC4308942  PMID: 25604647
Malaria; Angola; Benguela; Plasmodium falciparum; Epidemiology
22.  The Dental Health of primary school children living in fluoridated, pre-fluoridated and non-fluoridated communities in New South Wales, Australia 
BMC Oral Health  2015;15:9.
The Local Government Area of Gosford implemented a water fluoridation scheme in 2008. Therefore the opportunity was taken to record the dental health of primary school children aged 5–7 years prior to the fluoridation and compare the results with other communities in NSW with different access to fluoridated water. The aim was to compare the oral health of New South Wales (Australia)s 5–7 year olds living in fluoridated, and non- fluoridated communities. One of the areas was due to implement water fluoridation and is termed the pre-fluoridation site.
Pupils in the first year of Public and Catholic Schools in three areas of NSW were recruited. Class lists were used to draw a sample of approximately 900 per area. This number allowed for a non-response rate of up to 30 per cent and would give a sample sufficient numbers to allow statistical inferences to be drawn. Children whose parents consented received a dental examination and the clinical data was collected on mark sense cards.
In the 3 areas the proportion of children who received a dental examination varied; 77.5% (n = 825) for the fluoridated area, 80.1% (n = 781) for the pre-fluoridated area and 55.3% (n = 523) for the non-fluoridated area. The mean dmft was 1.40 for the fluoridated area, 2.02 for the pre-fluoridated area and 2.09 for the non-fluoridated area. These differences were statistically significant (p < 0.01). Differences were also noted in the proportion of children who were caries free, 62.6% fluoridated area, 50.8% for the pre-fluoride area and 48.6% for the non-fluoride location.
The children living in the well-established fluoridated area had less dental caries and a higher proportion free from disease when compared with the other two areas which were not fluoridated. Fluoridation demonstrated a clear benefit in terms of better oral health for young children.
PMCID: PMC4324770  PMID: 25604625
Water fluoridation; Dental caries; Children; Australia
23.  Cystatin C enhances GFR estimating Equations in Kidney Transplant Recipients 
American journal of nephrology  2014;39(1):59-65.
The glomerular filtration rate (GFR) estimating equation incorporating both cystatin C and creatinine perform better than those using creatinine or cystatin C alone in patients with reduced GFR. Whether this equation performs well in kidney transplant recipients cross-sectionally, and more importantly, over time has not been addressed.
We analyzed four GFR estimating equations in participants of the Angiotensin II Blockade for Chronic Allograft Nephropathy Trial (NCT 00067990): Chronic Kidney Disease Epidemiology Collaboration equations based on serum cystatin C and creatinine (eGFR (CKD-EPI-Creat+CysC)), cystatin C alone (eGFR (CKD-EPI-CysC)), creatinine alone (eGFR (CKD-EPI-Creat)) and the Modification of Diet in Renal Disease study equation (eGFR(MDRD)). Iothalamate GFR served as a standard (mGFR).
mGFR, serum creatinine, and cystatin C shortly after transplant were 56.1 ± 17.0 mL/min/1.73 m2, 1.2 ± 0.4 mg/dL, and 1.2 ± 0.3 mg/L respectively. eGFR (CKD-EPI-Creat+CysC) was most precise (R2=0.50) but slightly more biased than eGFR (MDRD); 9.0 ± 12.7 ml/min/1.73m2 vs. 6.4 ± 15.8 ml/min/1.73m2, respectively. This improved precision was most evident in recipients with mGFR >60 ml/min/1.73m2. For relative accuracy, eGFR (MDRD) and eGFR (CKD-EPI-Creat+CysC) had the highest percentage of estimates falling within 30% of mGFR; 75.8% and 68.9%, respectively. Longitudinally, equations incorporating cystatin C most closely paralleled the change in mGFR.
eGFR (CKD-EPI-Creat+CysC) is more precise and reflects GFR change over time reasonably well. eGFR (MDRD) had superior performance in recipients with mGFR between 30–60 ml/min/1.73m2.
PMCID: PMC4026030  PMID: 24457184
Glomerular filtration rate; Chronic Kidney Disease Epidemiology Collaboration; Modification of Diet in Renal Disease; cystatin C; kidney transplantation
24.  Potentiated Hsp104 variants antagonize diverse proteotoxic misfolding events 
Cell  2014;156(0):170-182.
There are no therapies that reverse the proteotoxic misfolding events that underpin fatal neurodegenerative diseases including amyotrophic lateral sclerosis (ALS) and Parkinson disease (PD). Hsp104, a conserved hexameric AAA+ protein from yeast, solubilizes disordered aggregates and amyloid, but has no metazoan homologue and only limited activity against human neurodegenerative disease proteins. Here, we reprogram Hsp104 to rescue TDP-43, FUS, and α-synuclein proteotoxicity by mutating single residues in helix 1, 2, or 3 of the middle domain or the small domain of nucleotide-binding domain 1. Potentiated Hsp104 variants enhance aggregate dissolution, restore proper protein localization, suppress proteotoxicity, and in a C. elegans PD model attenuate dopaminergic neurodegeneration. Potentiating mutations reconfigure how Hsp 104 subunits collaborate, desensitize Hsp104 to inhibition, obviate any requirement for Hsp70, and enhance ATPase, translocation, and unfoldase activity. Our work establishes that disease-associated aggregates and amyloid are tractable targets and that enhanced disaggregases can restore proteostasis and mitigate neurodegeneration.
PMCID: PMC3909490  PMID: 24439375
25.  Adjuvant Exemestane with Ovarian Suppression in Premenopausal Breast Cancer 
The New England journal of medicine  2014;371(2):107-118.
Adjuvant therapy with an aromatase inhibitor improves outcomes, as compared with tamoxifen, in postmenopausal women with hormone-receptor–positive breast cancer.
In two phase 3 trials, we randomly assigned premenopausal women with hormone-receptor–positive early breast cancer to the aromatase inhibitor exemestane plus ovarian suppression or tamoxifen plus ovarian suppression for a period of 5 years. Suppression of ovarian estrogen production was achieved with the use of the gonadotropin-releasing-hormone agonist triptorelin, oophorectomy, or ovarian irradiation. The primary analysis combined data from 4690 patients in the two trials.
After a median follow-up of 68 months, disease-free survival at 5 years was 91.1% in the exemestane–ovarian suppression group and 87.3% in the tamoxifen–ovarian suppression group (hazard ratio for disease recurrence, second invasive cancer, or death, 0.72; 95% confidence interval [CI], 0.60 to 0.85; P<0.001). The rate of freedom from breast cancer at 5 years was 92.8% in the exemestane–ovarian suppression group, as compared with 88.8% in the tamoxifen–ovarian suppression group (hazard ratio for recurrence, 0.66; 95% CI, 0.55 to 0.80; P<0.001). With 194 deaths (4.1% of the patients), overall survival did not differ significantly between the two groups (hazard ratio for death in the exemestane–ovarian suppression group, 1.14; 95% CI, 0.86 to 1.51; P = 0.37). Selected adverse events of grade 3 or 4 were reported for 30.6% of the patients in the exemestane–ovarian suppression group and 29.4% of those in the tamoxifen–ovarian suppression group, with profiles similar to those for postmenopausal women.
In premenopausal women with hormone-receptor–positive early breast cancer, adjuvant treatment with exemestane plus ovarian suppression, as compared with tamoxifen plus ovarian suppression, significantly reduced recurrence. (Funded by Pfizer and others; TEXT and SOFT numbers, NCT00066703 and NCT00066690, respectively.)
PMCID: PMC4175521  PMID: 24881463

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