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Military training exercises are conducted routinely in the Mojave Desert. To determine whether assignment in this desert environment increases risk of respiratory illnesses, hospitalization rates were compared between two matched cohorts of soldiers during three intervals of follow-up during a 10-year surveillance period. The exposed cohort (N = 21,543) included all soldiers who were ever assigned to the Mojave Desert during the surveillance period. The control cohort (N = 86,172) included soldiers matched on demographic characteristics who were never assigned to the Mojave Desert during the surveillance period. Three follow-up intervals ("before," "during," "after") were defined relative to times when exposed soldiers were assigned to the desert. Rates of respiratory hospitalizations were similar between the cohorts for the "before" and "during" intervals but were higher in the exposed cohort for the "after" interval (rate ratio, 1.30; 95% confidence interval, 1.07-1.59). This difference was largely attributable to excess pneumonia and influenza hospitalizations in the exposed cohort. Healthy, young adults may have increased susceptibility to respiratory infectious illnesses after prolonged exposures to desert environments. [ABSTRACT FROM AUTHOR]

Background: In the United States, the leading cause of death for young men is unintentional injury. The experience of the U.S. Army, because it comprises mostly young men, provides insights into factors associated with risk of accidental death. Between 1990 and 1998, accidents accounted for more than half of all deaths of men on active duty in the U.S. Army.Methods: All men on active duty in the U.S. Army who died in an accident between 1990 and 1998 were included in the study. For each accidental death case, four randomly selected controls were also included, matched on gender and contemporaneous military service.Results: In multivariate analyses, accidental death victims were more likely to be unmarried, limited to a high school education, in combat-specific occupations, veterans of a recent deployment, and previously hospitalized for an "injury/poisoning," "mental disorder," or "sign/symptom/ill-defined condition." Of behaviors reported on routine health risk assessments, the strongest predictor of a subsequent fatal accident was motorcycle use while the most excess deaths were attributable to consuming more than five alcoholic drinks per week.Conclusions: There are characteristics, experiences, and behaviors that predict accidental death risk. The findings may inform safety and health promotion programs aimed at young adults. [ABSTRACT FROM AUTHOR]

Prevention activities are designed and resourced based on perceptions of the relative population health impacts of various conditions. We examined the nature and variability of rankings of "conditions" based on how they are defined and how their population health impacts are measured. The first listed diagnosis from all hospitalizations and ambulatory visits of U.S. service members during 2002 was used to rank conditions (as defined by two standard classification systems) using five different measures of population health impacts. Less than 10% of all conditions accounted for more than one-half of total population health impact, regardless of how conditions were defined or impacts measured. However, specific conditions with the largest impacts varied depending on the classification system and impact measure. Four groups of related conditions--acute musculoskeletal injuries, pregnancy-related conditions, respiratory infections, and mental disorders (including substance abuse)--accounted for disproportionately large impacts regardless of the measure. The identification of conditions with the largest population health impacts depends on the nature and degree of aggregation in defining conditions and the measure of impact. The findings are relevant to prevention planning and resourcing. [ABSTRACT FROM AUTHOR]

Basic trainees at Fort Jackson, South Carolina, who were unable to continue basic combat training (BCT) because of a serious injury were assigned to the Physical Training and Rehabilitation Program (PTRP). Between January 3, 1998 and July 24, 2001, 4258 trainees were assigned to the PTRP. Using a retrospective cohort study design, return to training and BCT graduation rates were evaluated. PTRP graduates were compared with matched non-PTRP graduates for 2-year retention in the Army. More PTRP women than men were discharged from the PTRP (60% and 48%, respectively, p < 0.01). Of PTRP trainees returning to BCT, 10% and 12% of men and women, respectively, were discharged from the Army compared with overall Fort Jackson discharge rates of 9% and 15% for men and women, respectively. Comparing PTRP graduates to matched non-PTRP graduates, there were no differences in 2-year retention for men (14.9% and 14.7%, respectively; p = 0.93) or women (26.6% and 30.1%, respectively; p = 0.19). Despite the high discharge rate in the PTRP, the BCT discharge rate for trainees who successfully rehabilitated was similar to the overall discharge rate at Fort Jackson. The 2-year retention in service for PTRP trainees who graduated from BCT was similar to that of non-PTRP trainees. [ABSTRACT FROM AUTHOR]

The DC-DC converter is an essential subsystem in electric vehicle (EV) chargers, and most converters depend on a single-input single-output structure, which can be costly when multiple charging units are needed. Additionally, these converters offer limited voltage gain, restricting charging configurations. This paper proposed a dual-stage high-gain converter that operates in a boost mode with reduced components, using an inductor, capacitor, and 2-diodes (LC2D) to provide high-gain output. The proposed Dual Inputs and Dual Outputs (DIDO) converter tied with Photovoltaic (PV) and constant DC acting as inputs and two different voltage levels EV chargers are serving as the output. The proposed converter operates at continuous conduction mode (CCM), achieving high efficiency and reliability with fewer losses. The proposed work was designed for 418V and 85V systems in MATLAB/Simulink, and the results were validated with hardware implementation. The proposed converter delivers high-gain output to the electric vehicle application with 92.2 % efficiency., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

Lignin is the main plant cell wall component responsible for recalcitrance in the process of lignocellulosic biomass conversion into biofuels. The recalcitrance and insolubility of lignin in different reaction media are due in part to the hydrogen bonds and π interactions that hold syringyl (S) and guaiacyl (G) units together and promote the formation of stable water-bridged dimeric complexes (WBDCs): S⋯G and S⋯S, in native lignin. The current understanding of how each type of interaction influences the stability of these complexes within lignin native cell walls is still limited. Here, we found by DFT calculations that hydrogen bonding is more dominant than π-stacking interaction between aromatic rings of WBDCs. Although there is a stronger interaction of hydrogen bonds between subunits and water and higher π-stacking interaction in the S⋯S complex compared to the S⋯G complex, the former complex is less thermodynamically stable than the latter due to the entropic contribution coming from the methoxy substituents in the S-unit. Our results demonstrate that the methoxylation degree of lignin units does not significantly influence the structural geometries of WBDCs; if anything, an enhanced dispersion interaction between ring aromatics results in quasi-sandwich geometries as found in "coiled" lignin structures in the xylem tissue of wood. In the same way as that with ionic liquids, polar solvents can dissolve S-lignin by favorable interactions with the aliphatic hydroxyl group in the α-position as the key site or the aromatic hydroxyl group as the secondary site.

In this international study, we examined the incidence of hip fractures, postfracture treatment, and all-cause mortality following hip fractures, based on demographics, geography, and calendar year. We used patient-level healthcare data from 19 countries and regions to identify patients aged 50 years and older hospitalized with a hip fracture from 2005 to 2018. The age- and sex-standardized incidence rates of hip fractures, post-hip fracture treatment (defined as the proportion of patients receiving anti-osteoporosis medication with various mechanisms of action [bisphosphonates, denosumab, raloxifene, strontium ranelate, or teriparatide] following a hip fracture), and the all-cause mortality rates after hip fractures were estimated using a standardized protocol and common data model. The number of hip fractures in 2050 was projected based on trends in the incidence and estimated future population demographics. In total, 4,115,046 hip fractures were identified from 20 databases. The reported age- and sex-standardized incidence rates of hip fractures ranged from 95.1 (95% confidence interval [CI] 94.8-95.4) in Brazil to 315.9 (95% CI 314.0-317.7) in Denmark per 100,000 population. Incidence rates decreased over the study period in most countries; however, the estimated total annual number of hip fractures nearly doubled from 2018 to 2050. Within 1 year following a hip fracture, post-hip fracture treatment ranged from 11.5% (95% CI 11.1% to 11.9%) in Germany to 50.3% (95% CI 50.0% to 50.7%) in the United Kingdom, and all-cause mortality rates ranged from 14.4% (95% CI 14.0% to 14.8%) in Singapore to 28.3% (95% CI 28.0% to 28.6%) in the United Kingdom. Males had lower use of anti-osteoporosis medication than females, higher rates of all-cause mortality, and a larger increase in the projected number of hip fractures by 2050. Substantial variations exist in the global epidemiology of hip fractures and postfracture outcomes. Our findings inform possible actions to reduce the projected public health burden of osteoporotic fractures among the aging population. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)., (© 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).)

Aims: The objectives were to describe differences in self-reported health at discharge between women diagnosed with angina or unspecific chest pain and investigate the association between self-reported health and adverse outcomes within 3 years., Methods and Results: Data from a national cohort study were used, including data from the DenHeart survey combined with 3 years of register-based follow-up. The population included two groups of women with symptoms of angina but no diagnosis of obstructive coronary artery disease at discharge (women with angina and women with unspecific chest pain). Self-reported health measured with validated instruments was combined with register-based follow-up on adverse outcomes (a composite of unplanned cardiac readmissions, revascularization, or all-cause mortality). Associations between self-reported health and time to first adverse outcomes were investigated with Cox proportional hazard models, reported as hazards ratios with 95% confidence intervals. In total, 1770 women completed the questionnaire (49%). Women with angina (n = 931) reported significantly worse self-reported health on several outcomes compared to women with unspecific chest pain (n = 839). Within the 3 years follow-up, women with angina were more often readmitted (29 vs. 23%, P = 0.011) and more underwent revascularization (10 vs. 1%, P < 0.001), whereas mortality rates were similar (4 vs. 4%, P = 0.750). Self-reported health (physical and mental) was associated with adverse outcomes between both groups (on most instruments)., Conclusion: Women with angina reported significantly worse self-reported health on most instruments compared to women with unspecific chest pain. Adverse outcomes varied between groups, with women diagnosed with angina experiencing more events., Registration: ClinicalTrials.gov (NCT01926145)., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Protective immune responses against respiratory pathogens, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza virus, are initiated by the mucosal immune system. However, most licensed vaccines are administered parenterally and are largely ineffective at inducing mucosal immunity. The development of safe and effective mucosal vaccines has been hampered by the lack of a suitable mucosal adjuvant. In this study we explore a class of adjuvant that harnesses mucosal-associated invariant T (MAIT) cells. We show evidence that intranasal immunization of MAIT cell agonists co-administered with protein, including the spike receptor binding domain from SARS-CoV-2 virus and hemagglutinin from influenza virus, induce protective humoral immunity and immunoglobulin A production. MAIT cell adjuvant activity is mediated by CD40L-dependent activation of dendritic cells and subsequent priming of T follicular helper cells. In summary, we show that MAIT cells are promising vaccine targets that can be utilized as cellular adjuvants in mucosal vaccines., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

To determine denosumab's effectiveness for fracture prevention among postmenopausal women with osteoporosis in East Asia, the risk of fracture was compared between patients continuing denosumab therapy versus patients discontinuing denosumab after one dose. The real-world effectiveness was observed to be consistent with the efficacy demonstrated in the phase III trial., Introduction: After therapeutic efficacy is demonstrated for subjects in global clinical trials, real-world evidence may provide complementary knowledge of therapeutic effectiveness in a heterogeneous mix of patients seen in clinical practice. This retrospective cohort study was conducted to compare the fracture risk in real-world clinical care received in Taiwan and Hong Kong between a treatment cohort (patients receiving denosumab 60 mg subcutaneously every 6 months) versus an off-treatment cohort (patients discontinuing after 1 dose of denosumab, which has no known clinical benefit) among real-world postmenopausal women., Methods: This study included 38,906 and 2,835 postmenopausal women receiving denosumab in Taiwan and Hong Kong, respectively. The primary endpoint was hip fracture, and secondary endpoints were clinical vertebral and nonvertebral fractures. Propensity-score-matched analysis, adjusting for known covariates, was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). The robustness of findings was evaluated with a series of sensitivity and quantitative bias analyses., Results: In this study, 554 hip fractures were included in the primary Taiwan population analysis. The crude incidence rate was 0.9 per 100 person-years in the treatment cohort (n = 25,059) and 1.7 per 100 person-years in the off-treatment cohort (n = 13,847). After adjusting for prognostic differences between cohorts, denosumab reduced the risk of hip fractures by 38% (HR = 0.62, CI:0.52-0.75). Risk reductions of similar magnitude were observed for the secondary endpoints and for the analysis of the smaller Hong Kong population., Conclusion: The effectiveness of denosumab for fracture reduction among real-world postmenopausal women with osteoporosis was consistent with the efficacy demonstrated in a global clinical trial., Registration: EnCePP registration number: EUPAS26372; registration date: 12/11/2018., (© 2022. The Author(s).)

On June 23, 2020, Prolia ® (denosumab) was approved by the National Medical Products Administration (NMPA) in the People's Republic of China as the first monoclonal antibody for the treatment of postmenopausal women with osteoporosis at high risk of fractures. Its brand name in Chinese is , a transliteration from the English name "Prolia", which has an implied meaning of "to give strength to everyone"- a suitable name for a potent anti-resorptive therapy. The approval was supported by a novel marketing authorization application (MAA) that included data from Prolia's global clinical trial program establishing favorable efficacy and safety, augmented by results from a real-world evidence (RWE) study confirming the effectiveness and safety of Prolia in clinical practice within Taiwan and Hong Kong. Key constructs for this registration-quality RWE study included the fit-for-purpose assessment of data quality, methodology and quantitative assessment of potential biases, good practices of study conduct, and reproducibility of results. Using data from clinical practice in Taiwan and Hong Kong to evaluate the benefits versus risks of Prolia treatment in ethnic Chinese women with postmenopausal osteoporosis, the RWE study results for effectiveness were comparable to efficacy demonstrated in the global clinical trial program and results for safety were consistent with the incidence observed in global post-marketing safety studies. While RWE is often used to monitor postmarket safety of drug products, support health insurance coverage decisions, and inform clinicians on real-world use of medicines, it has not been widely used to support regulatory approval for new medicines in lieu of clinical bridging studies in countries where such studies are required. Well-conducted registrational RWE studies can play a pivotal role in complementing the totality of evidence presented in an MAA. The benefits of such an approach include avoiding the collection of additional placebo-controlled trial data in populations where adequate ethnic characterization of efficacy, effectiveness, and safety may already exist from postmarketing sources, and accelerate access for patients to innovative medicines in important regions. Here, we describe a regulatory case study of a novel MAA incorporating RWE that provided important evidence to confirm the benefit:risk of a new drug and facilitated a label expansion to a new patient population., (© 2021. The Author(s).)

Background: In South Korea, women aged 66 years are eligible for complimentary bone mineral density (BMD) screening via the National Screening Program for Transitional Ages. We aimed to evaluate the 10-year fracture risk in women receiving BMD screening between January 2008 and December 2015., Methods: BMD was classified as normal (T-score ≥-1.0 standard deviation [SD]), osteopenia (T-score <-1.0 SD and >-2.5 SD), and osteoporosis (T score ≤-2.5 SD) from dual-energy X-ray absorptiometry. Follow-up continued from the screening date until a diagnosis for clinical fragility fracture (including sites of the vertebrae, hip, pelvis, clavicle, humerus, forearm, wrist, lower leg, and ankle), censored at the earliest date of trauma, death, or December 2017; fracture was ascertained using diagnostic codes from the National Health Insurance Service database. A multivariable Cox proportional hazard model was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of fracture in women with osteopenia or osteoporosis relative to women with normal BMD., Results: Among the 271,197 women screened, 44.0% had osteopenia and 35.2% had osteoporosis. The 10 year cumulative incidence of fragility fractures was 31.1%, 37.5%, and 44.3% in women with normal BMD, osteopenia, and osteoporosis, respectively. Fracture risk was higher in women with osteopenia (HR, 1.31; 95% CI, 1.28 to 1.34) and osteoporosis (HR, 1.68; 95% CI, 1.64 to 1.72) than in women with normal BMD., Conclusion: Women with osteopenia and women with osteoporosis, identified by the national BMD screening program, demonstrated a substantially elevated risk of fracture.

Background: A research priority in finding a cure for HIV is to establish methods to accurately locate and quantify where and how HIV persists in people living with HIV (PLWH) receiving suppressive antiretroviral therapy (ART). Infusing copper-64 ( 64 Cu) radiolabelled broadly neutralising antibodies targeting HIV envelope (Env) with CT scan and positron emission tomography (PET) identified HIV Env in tissues in SIV infected non-human primates . We aimed to determine if a similar approach was effective in people living with HIV (PLWH)., Methods: Unmodified 3BNC117 was compared with 3BNC117 bound to the chelator MeCOSar and 64 Cu ( 64 Cu-3BNC117) in vitro to assess binding and neutralization. In a clinical trial 64 Cu-3BNC117 was infused into HIV uninfected (Group 1), HIV infected and viremic (viral load, VL >1000 c/mL; Group 2) and HIV infected aviremic (VL <20 c/mL; Group 3) participants using two dosing strategies: high protein (3mg/kg unlabeled 3BNC117 combined with <5mg 64 Cu-3BNC117) and trace (<5mg 64 Cu-3BNC117 only). All participants were screened for 3BNC117 sensitivity from virus obtained from viral outgrowth. Magnetic resonance imaging (MRI)/PET and pharmacokinetic assessments (ELISA for serum 3BNC117 concentrations and gamma counting for 64 Cu) were performed 1, 24- and 48-hours post dosing. The trial (clincialtrials.gov NCT03063788) primary endpoint was comparison of PET standard uptake values (SUVs) in regions of interest (e.g lymph node groups and gastrointestinal tract)., Findings: Comparison of unmodified and modified 3BNC117 in vitro demonstrated no difference in HIV binding or neutralisation. 17 individuals were enrolled of which 12 were dosed including Group 1 (n=4, 2 high protein, 2 trace dose), Group 2 (n=6, 2 high protein, 4 trace) and Group 3 (n=2, trace only). HIV+ participants had a mean CD4 of 574 cells/microL and mean age 43 years. There were no drug related adverse effects and no differences in tissue uptake in regions of interest (e.g lymph node gut, pharynx) between the 3 groups. In the high protein dosing group, serum concentrations of 3BNC117 and gamma counts were highly correlated demonstrating that 64 Cu-3BNC117 remained intact in vivo., Interpretation: In PLWH on or off ART, the intervention of infusing 64 Cu-3BNC117 and MRI/PET imaging over 48 hours, was unable to detect HIV-1 env expression in vivo. Future studies should investigate alternative radiolabels such as zirconium which have a longer half-life in vivo., Funding: Funded by the Alfred Foundation, The Australian Centre for HIV and Hepatitis Virology Research with additional support from the Division of AIDS, National Institute of Allergy and Infectious Disease, US National Institutes of Health (USAI126611). JHM and SRL are supported by the Australian National Health and Medical Research Council., Competing Interests: Declaration of Competing Interest PD holds intellectual property in, this area of research, which has been licensed from the University of Melbourne to Clarity Pharmaceuticals and has a financial interest in Clarity Pharmaceuticals. PD serves on the Scientific Advisory Board of Clarity Pharmaceuticals. MCN has a patent for 3BNC117 licensed to Gilead and is a Member of the Scientific Advisory Board of Celldex Pharmaceuticals and Frontier Bioscience. SRL reports grants from National Health and Medical Research Council of Australia (NHMRC), grants from National Institutes of Health (NIH), during the conduct of the study; grants from American Foundation for AIDS Research (amfAR), grants from Gilead Sciences, grants from Merck, grants from ViiV, grants from Leidos, grants from Wellcome Trust, grants from Australian Centre for HIV and Hepatitis Virology Research (ACH2), grants from Melbourne HIV Cure Consortium, grants from Victorian Department of Health and Human Services (DHHS), grants from Medical Research Future Fund (MRFF), Other authors have nothing to disclose., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

The midwifery and occupational health faculty of a U.S. university were approached by parish and health care leaders from Caldwell, Liberia, for assistance in addressing critical maternal health care needs in their community. Liberia has suffered setbacks in its efforts to improve health care for its people due to recent civil wars and the Ebola epidemic of 2014 to 2016. Initial discussions among international groups centered around realistic ways to help in the face of multiple compelling needs. Grant support for U.S. faculty to conduct exploratory meetings and educational workshops in Liberia was secured. Ethical principles and best practices in partnering across borders guided this partnership and include reciprocity, equity, and empowerment of health care workers, including nurses, midwives, community workers, and health center staff. Here, we describe the preparation for and implementation of these workshops, as well as plans for continuing collaborations that emerged from these workshops., (Copyright © 2020 AWHONN. Published by Elsevier Inc. All rights reserved.)

A variant of 1,4,7,10-tetraazacyclododecane (cyclen) bearing two semicarbazone pendant groups has been prepared. The octadentate ligand forms complexes with Bi3+ and Pb2+. X-ray crystallography showed that the neutral ligand provides an eight-coordinate environment for both metal ions and intermolecular hydrogen bond interactions have influenced the coordination environments of both complexes in the solid state. NMR spectroscopy revealed a fluxional environment for both complexes. The ligand was radiolabeled with the α-emitting radioactive isotope 213Bi3+, which is used in systemic targeted radiotherapy. The resulting complex was stable in serum for at least 90 min (two decay half-lives). The Pb2+ complex has reasonably fast kinetics of formation (t1/2 = 20 min) at 25 °C and pH 7.4. The Bi3+ and Pb2+ complexes show kinetic stability in 1.2 M HCl (half-lives of 214 min and 47 min, respectively). This is the first description of a macrocycle bearing semicarbazone pendant groups and its utility in coordinating main group metals, specifically those with radiotherapeutic potential.

The current advances in nanoengineered materials coupled with the precise targeting capability of recombinant antibodies can create nanoscale diagnostics and therapeutics which show enhanced accumulation and extended retention at a target tissue. Smaller antibodies such as single-chain variable fragments (scFv) preserve the selective and strong binding of their parent antibody to their antigen with the benefits of low immunogenicity, more efficient tissue penetration and easy introduction of functional residues suitable for site-specific conjugation. This is of high importance as nonspecific antibody modification often involves attachment to free cysteine or lysine amino acids which may reside in the active site, leading to reduced antigen binding.In this chapter, we outline a facile and versatile chemoenzymatic approach for production of targeted nanocarrier scFv conjugates using the bacterial trans-peptidase Sortase A (Srt A). Srt A efficiently mediates sequence-specific peptide ligation under mild conditions and has few undesirable side reactions. We first describe the production, purification and characterization of Srt A enzyme and a scFv construct which targets activated platelets, called scFv anti-GPIIb/IIIa . Following this, our protocol illustrates the chemoenzymatic modification of the antibody at the C-terminus with an orthogonal click chemistry linker. This avoids any random attachment to the biologically active antigen binding site of the antibody. Finally, we describe the modification of a nanoparticle surface with scFv attachment via two methods: (1) direct Sortase-mediated conjugation; or (2) a two-step system which consists of scFv Sortase-mediated conjugation followed by strain promoted azide-alkyne cycloaddition. Finally, methodology is described to assess the successful assembly of targeted particles.

Background: Individuals who suffer from mental illness are more prone to obesity and related co-morbidities, including the metabolic syndrome. Autopsies provide an outstanding platform for the macroscopic, microscopic and molecular-biological investigation of diseases. Autopsy-based findings may assist in the investigation of the metabolic syndrome. To utilise the vast information that an autopsy encompasses to elucidate the pathophysiology behind the syndrome further, we aimed to both develop and evaluate a method for the post mortem definition of the metabolic syndrome., Methods: Based on the nationwide Danish SURVIVE study of deceased mentally ill, we established a set of post mortem criteria for each of the harmonized criteria of the metabolic syndrome. We based the post mortem (PM) evaluation on information from the police reports and the data collected at autopsy, such as anthropometric measurements and biochemical and toxicological analyses (PM information). We compared our PM evaluation with the data from the Danish health registries [ante mortem (AM) information, considered the gold standard] from each individual., Results: The study included 443 deceased individuals (272 male and 171 female) with a mean age of 50.4 (± 15.5) years and a median (interquartile range) post mortem interval of 114 (84-156) hours. We found no significant difference when defining the metabolic syndrome from the PM information in comparison to the AM information ( P  = 0.175). The PM evaluation yielded a high specificity (0.93) and a moderate sensitivity (0.63) with a moderate level of agreement compared to the AM evaluation (Cohen's κ = 0.51). Neither age nor post mortem interval affected the final results., Conclusions: Our model of a PM definition of the metabolic syndrome proved reliable when compared to the AM information. We believe that an appropriate estimate of the prevalence of the metabolic syndrome can be established post mortem. However, while neither the PM nor the AM information is exhaustive in terms of defining an individual's health status, a superlative estimate may be obtained by combining the PM and the AM information. With this model, we open up the possibility of utilising autopsy data for future studies of the metabolic syndrome.

Background Stroke is the fifth leading cause of death in young individuals globally. Data on the burden of sudden death by stroke are sparse in the young. Aims The aim of this study was to report mortality rates, cause of death, stroke subtype, and symptoms in children and young adults who suffered sudden death by stroke. Methods We conducted a retrospective, nationwide study including all deaths within Danish borders between 2000-2009 and 2007-2009 in persons aged 1-35 years and 36-49 years, respectively. Two physicians identified all sudden death cases through review of all death certificates. All available autopsy reports and records from hospitals and general practitioners were retrieved and a neurologist identified all sudden death by stroke cases. Results Of the 14,567 deaths in the 10-year period, there were 1,698 sudden death cases, of which 52 (3%) were sudden death by stroke. There was a male predominance (56%) and the median age was 33 years. The incidence of sudden death by stroke in individuals aged 1-49 years was 0.19 deaths per 100,000 person-years. Stroke was hemorrhagic in 94% of cases, whereof subarachnoid hemorrhage was the cause of death in 63% of cases. Seventeen (33%) cases contacted the healthcare system because of neurological symptoms, whereof one was suspected of having a stroke (6%). Conclusions Sudden death by stroke in children and young adults occurs primarily due to hemorrhagic stroke. We report a high frequency of neurological symptoms prior to sudden death by stroke. Increased awareness among healthcare professionals towards stroke symptoms in children and young adults may lead to earlier detection of stroke, and thereby potentially lowering the incidence of sudden death by stroke.

Background: The use of prophylactic systemic antibiotics with nasal packing has been a controversial topic. There are few evidence-based studies to determine the need for prophylactic systemic antibiotics. We performed a systematic literature review to determine the role of prophylactic systemic antibiotics with nasal packing in the prevention of toxic shock syndrome and local nasal infections., Objective: The purpose of this study was to perform a systematic literature review to determine the role of prophylactic systemic antibiotics with nasal packing in the prevention of toxic shock syndrome and local nasal infections., Methods: A search for studies that reviewed the efficacy of prophylactic systemic antibiotics in the prevention of toxic shock or nasal infections and/or sinusitis for patients with nasal packing for epistaxis and postoperative septoplasties was performed. This was conducted in a number of medical literature data bases by following the methods of the 2009 Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Only English publications and human studies that were randomized control trials, quasi-randomized control trials, controlled clinical trials, retrospective studies, and case series were included., Results: Six studies, with a total of 990 patients, met the inclusion criteria for the review and were included. Primary outcomes were signs and symptoms of nasal or sinus infections in patients who underwent nasal packing for epistaxis or septoplasty. There were no reports of toxic shock syndrome in any patients, and there was no statistical difference in purulent drainage in patients who had septoplasty (9.9 versus 11.2%) treated with or without antibiotics., Conclusion: There is a paucity of literature that reviewed the need for prophylactic systemic antibiotics with nasal packing. The available literature does not show a significant benefit to the use of antibiotics with nasal packing, but the studies were underpowered to detect such a difference. One must consider the associated risks of prophylactic antibiotics to the patient as well when deciding to prescribe prophylactic antibiotics.

Background: Sudden cardiac death caused by coronary artery disease (CAD-SCD) is the most frequent cause of SCD in persons <50years. The aim of this study was to examine differences in clinical characteristics and autopsy findings of the heart among 18-35 and 36-49year old CAD-SCD cases., Methods: We have previously identified all sudden cardiac deaths in Denmark through review of death certificates and autopsy reports including all deaths between 2000 and 2006 in individuals aged 18-35years and all deaths between 2007 and 2009 in individuals aged 18-49years. In this study we included the 197 autopsied CAD-SCD cases. Full autopsy report and medical records from general practitioners and hospitals were obtained., Results: There was a male predominance (n=151, 76%) and the median age was 42years. In witnessed cases, 51% had a shockable rhythm and 9 cases returned to spontaneous circulation briefly, CAD-SCD victims aged 36-49years had more severe atherosclerosis in all coronary arteries, more multi-vessel disease (29% vs. 15%, p=0.049) and less commonly (38% vs. 54%, p=0.039) acute coronary occlusion than victims <36years. Sixty-eight percent(n=133) of CAD-SCD victims had cardiac symptoms prior to death., Conclusion: This nationwide study found several differences in the pathologic lesions of the heart in victims aged 18-35 and 36-49years, which might be associated with different disease progression leading to death in these age groups. We also report a high frequency of cardiac symptoms prior to death in young CAD-SCD cases, which may enable clinicians to prevent these tragic deaths., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The importance of women's oral health and its association with overall systemic health cannot be overemphasized. Poor oral health can have several detrimental effects on a woman's health across her life span. This article reviews the literature and describes how nurses, nurse practitioners, and nurse-midwives can incorporate oral cavity examinations into their care of women., (© 2017, AWHONN. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).)

Gallium-68 is a positron-emitting isotope that can be used in positron-emission tomography imaging agents. Alzheimer's disease is associated with the formation of plaques in the brain primarily comprised of aggregates of a 42 amino acid protein called amyloid-β. With the goal of synthesising charge neutral, low molecular weight, lipophilic gallium complexes with the potential to cross the blood-brain barrier and bind to Aβ plaques we have used an ancillary tetradentate N 2 O 2 Schiff base ligand and the β-diketone curcumin as a bidentate ligand to give a six-coordinate Ga 3+ complex. The tetradentate Schiff base ligand adopts the cis-β configuration with deprotonated curcumin acting as a bidentate ligand. The complex binds to amyloid-β plaques in human brain tissue and it is possible that extension of this chemistry to positron-emitting gallium-68 could provide useful imaging agents for Alzheimer's disease., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Introduction: There is a shortage of primary care providers in the United States. As more individuals obtain health insurance coverage with the Patient Protection and Affordable Care Act, the number seeking care will increase dramatically. Both the Institute of Medicine and the American College of Nurse-Midwives state that certified nurse-midwives and certified midwives should function at their full scope of practice, which includes primary care services as delineated by the Core Competencies for Basic Midwifery Practice. Nonetheless, the percentage of midwives who self-identify as primary care providers is decreasing. Dedicated primary care educational experiences may increase student confidence and encourage the incorporation of primary care into midwifery practice after graduation., Methods: Midwifery students in 2 cohorts completed questionnaires before and after a dedicated primary care practicum to study changes in the perceived level of confidence in primary care provision. The students in cohort A participated in 45 hours of primary care clinical time, whereas the students in cohort B participated in 88 hours of primary care clinical time. Postclinical focus groups provided qualitative data on student perceptions and attitudes about the clinical experience. Student responses were coded by cohort and analyzed using qualitative descriptive analysis., Results: Seventeen midwifery students from 2 cohorts completed questionnaires. Students in both cohorts reported increased perceived confidence in almost all primary care domains., Discussion: Participation in a dedicated primary care clinical rotation increased student-perceived confidence in primary care practice. The inclusion of designated primary care clinical education in nurse-midwifery education may contribute to meeting the national need for primary care providers. This article is part of a special series of articles that address midwifery innovations in clinical practice, education, interprofessional collaboration, health policy, and global health., (© 2015 by the American College of Nurse-Midwives.)

Introduction: More than 70 common alleles are known to be involved in breast cancer (BC) susceptibility, and several exhibit significant heterogeneity in their associations with different BC subtypes. Although there are differences in the association patterns between BRCA1 and BRCA2 mutation carriers and the general population for several loci, no study has comprehensively evaluated the associations of all known BC susceptibility alleles with risk of BC subtypes in BRCA1 and BRCA2 carriers., Methods: We used data from 15,252 BRCA1 and 8,211 BRCA2 carriers to analyze the associations between approximately 200,000 genetic variants on the iCOGS array and risk of BC subtypes defined by estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and triple-negative- (TN) status; morphologic subtypes; histological grade; and nodal involvement., Results: The estimated BC hazard ratios (HRs) for the 74 known BC alleles in BRCA1 carriers exhibited moderate correlations with the corresponding odds ratios from the general population. However, their associations with ER-positive BC in BRCA1 carriers were more consistent with the ER-positive associations in the general population (intraclass correlation (ICC) = 0.61, 95% confidence interval (CI): 0.45 to 0.74), and the same was true when considering ER-negative associations in both groups (ICC = 0.59, 95% CI: 0.42 to 0.72). Similarly, there was strong correlation between the ER-positive associations for BRCA1 and BRCA2 carriers (ICC = 0.67, 95% CI: 0.52 to 0.78), whereas ER-positive associations in any one of the groups were generally inconsistent with ER-negative associations in any of the others. After stratifying by ER status in mutation carriers, additional significant associations were observed. Several previously unreported variants exhibited associations at P <10(-6) in the analyses by PR status, HER2 status, TN phenotype, morphologic subtypes, histological grade and nodal involvement., Conclusions: Differences in associations of common BC susceptibility alleles between BRCA1 and BRCA2 carriers and the general population are explained to a large extent by differences in the prevalence of ER-positive and ER-negative tumors. Estimates of the risks associated with these variants based on population-based studies are likely to be applicable to mutation carriers after taking ER status into account, which has implications for risk prediction.

Background: Preparticipation screening programs have been suggested to reduce the numbers of sports-related sudden cardiac deaths (SrSCD)., Objective: The purpose of this study was to identify and characterize all SrSCD aged 12-49 years and to address the difference in incidence rates between competitive and noncompetitive athletes., Methods: All deaths among persons aged 12-49 years from 2007-2009 were included. Death certificates were reviewed. History of previous admissions to hospital was assessed, and discharge summaries and autopsy reports were read. Sudden cardiac deaths (SCDs) and SrSCD cases were identified., Results: In the 3-year period, there were 881 SCDs, of which we identified 44 SrSCD. In noncompetitive athletes aged 12-35 years, the incidence rate of SrSCD was 0.43 (95% confidence interval [CI] 0.16-0.94) per 100,000 athlete person-years vs 2.95 (95% CI 1.95-4.30) in noncompetitive athletes aged 36-49 years. In competitive athletes, the incidence rate of SrSCD was 0.47 (95% CI 0.10-1.14) and 6.64 (95% CI 2.86-13.1) per 100,000 athlete person-years in those aged 12-35 years and 36-49 years, respectively. The incidence rate of SCD in the general population was 10.7 (95% CI 10.0-11.5) per 100.000 person-years., Conclusion: The incidence rates of SrSCD in noncompetitive and competitive athletes are not different. The study showed an increase in the incidence rate of SrSCD in persons aged 36-49 years in both noncompetitive and competitive athletes compared to those aged 12-35 years. Importantly, SCD in the general population is much more prevalent than is SrSCD in all age groups., (Copyright © 2014 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Single Nucleotide Polymorphisms (SNPs) in genes involved in the DNA Base Excision Repair (BER) pathway could be associated with cancer risk in carriers of mutations in the high-penetrance susceptibility genes BRCA1 and BRCA2, given the relation of synthetic lethality that exists between one of the components of the BER pathway, PARP1 (poly ADP ribose polymerase), and both BRCA1 and BRCA2. In the present study, we have performed a comprehensive analysis of 18 genes involved in BER using a tagging SNP approach in a large series of BRCA1 and BRCA2 mutation carriers. 144 SNPs were analyzed in a two stage study involving 23,463 carriers from the CIMBA consortium (the Consortium of Investigators of Modifiers of BRCA1 and BRCA2). Eleven SNPs showed evidence of association with breast and/or ovarian cancer at p<0.05 in the combined analysis. Four of the five genes for which strongest evidence of association was observed were DNA glycosylases. The strongest evidence was for rs1466785 in the NEIL2 (endonuclease VIII-like 2) gene (HR: 1.09, 95% CI (1.03-1.16), p = 2.7 × 10(-3)) for association with breast cancer risk in BRCA2 mutation carriers, and rs2304277 in the OGG1 (8-guanine DNA glycosylase) gene, with ovarian cancer risk in BRCA1 mutation carriers (HR: 1.12 95%CI: 1.03-1.21, p = 4.8 × 10(-3)). DNA glycosylases involved in the first steps of the BER pathway may be associated with cancer risk in BRCA1/2 mutation carriers and should be more comprehensively studied.

Background: Knowledge of the burden and causes of sudden cardiac death (SCD) is sparse in persons aged<50 years; better understanding is needed to lower the risk of SCD. The aim of this study was to report SCD incidence rates and autopsy findings in persons aged 1 to 49 years., Methods and Results: All deaths in persons aged 1 to 49 years were included in 2007 to 2009. Death certificates were reviewed by 2 physicians. History of previous admissions to hospital was assessed, and discharge summaries were read. Sudden unexpected death cases were identified and autopsy reports were collected. In the 3-year study period, there were 7849 deaths of which we identified 893 (11%) SCD cases. The annual incidence rate per 100 000 persons increased from 2.3 (95% confidence interval, 2.0-2.7) to 21.7 (95% confidence interval, 20.2-23.4) in persons aged 1 to 35 and 36 to 49 years, respectively. Coronary artery disease was the most common cause of death and was found in 158 (36%) autopsied cases, followed by 135 (31%) cases of sudden unexplained death., Conclusions: In a nationwide cohort of persons aged<50 years, the annual incidence rate of SCD was ≈10× higher in persons aged 36 to 49 years than in persons aged 1 to 35 years. Notably, coronary artery disease was the most common cause of SCD, followed by unexplained deaths. These findings may help in developing strategies to prevent SCD in the future.

Unlabelled: This observational study showed that after 2 years, both risedronate and alendronate lowered the risk of hip and nonvertebral fractures compared with patients filling in a single bisphosphonate prescription., Introduction: Post hoc analyses of the placebo-controlled trials suggested earlier effects for risedronate (6-12 months) than for alendronate (18-24 months). The present study extends our 1-year observational data that confirmed an earlier fracture reduction with risedronate and evaluated the absolute and relative effectiveness of alendronate and risedronate in clinical practice over 2 years., Methods: We observed three cohorts of women aged 65 years and older who initiated once-a-week dosing of bisphosphonate therapy; (1) patients adherent to alendronate (n = 21,615), (2) patients adherent to risedronate (n = 12,215), or (3) patients filling only a single bisphosphonate prescription (n = 5,390) as a referent population. Proportional hazard modeling compared the incidence of hip and nonvertebral fractures among the cohorts over 2 years after the initial prescription., Results: In this cohort, we previously showed at 12 months a significant reduction of hip and nonvertebral fractures with risedronate but not with alendronate. At the end of 2 years, the cumulative incidence of hip fractures in the referent cohort was 1.9 %, and incidence of nonvertebral fractures was 6.3 %. Relative to the referent, 6 months after initiating therapy and continuing through 2 years, both risedronate and alendronate cohorts had approximately a 45 % lower incidence of hip fractures and a 30 % lower incidence of nonvertebral fractures., Conclusion: These observations suggest that both risedronate and alendronate are effective at reducing the risk of hip and nonvertebral fracture after 2 years of treatment and support the post hoc analyses of placebo-controlled trials indicating an earlier effect of risedronate.

A pattern of genital injury that separates trauma seen in sexual assault cases from trauma seen following consensual sexual intercourse has been a matter of debate. This study aimed at clarifying the question by eliminating as many confounders as possible in a prospective, case-control setup. A total of 98 controls and 39 cases were examined using the naked eye, the colposcope and toluidine blue dye followed by colposcopy. The overall frequency of having at least one lesion was strikingly similar in the two groups, but cases had significantly more abrasions, a trend towards more haematomas and a higher frequency of multiple lesions. Cases had a higher frequency of lesions in locations other than the 6 o'clock position. Our data suggests that cases have larger, more complex lesions. In conclusion, this study has confirmed the existence of different patterns of genital lesions. Background data for detection of genital lesions using the three most commonly used techniques is provided. These results will aid in the interpretation of findings seen when examining sexual assault victims., (Copyright © 2013 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.)

Breast milk is considered the optimal form of nutrition for newborn infants. Current recommendations are to breastfeed for 6 months. Not all women are able to breastfeed. Mammary hypoplasia is a primary cause of failed lactogenesis II, whereby the mother is unable to produce an adequate milk volume. Women with mammary hypoplasia often have normal hormone levels and innervation but lack sufficient glandular tissue to produce an adequate milk supply to sustain their infant. The etiology of this rare condition is unclear, although there are theories that refer to genetic predisposition and estrogenic environmental exposures in select agricultural environments. Women with mammary hypoplasia may not exhibit the typical breast changes associated with pregnancy and may fail to lactate postpartum. Breasts of women with mammary hypoplasia may be widely spaced (1.5 inches or greater), asymmetric, or tuberous in nature. Awareness of the history and clinical signs of mammary hypoplasia during the prenatal period and immediate postpartum increases the likelihood that women will receive the needed education and physical and emotional support and encouragement. Several medications and herbs demonstrate some efficacy in increasing breast milk production in women with mammary hypoplasia., (© 2013 by the American College of Nurse-Midwives.)

The aim of this study was to evaluate interpretations and the reproducibility of interpretations when looking at colposcopic photographs in a forensic setting, as well as discussing some of the dilemmas and pitfalls of forensic colposcopic photography. A total of 316 colposcopic photographs from 51 women taken on three occasions following consensual sexual intercourse, and 78 colposcopic photographs from 39 rape victims, were evaluated by four different observers. Photographs were taken in the same setting, by the same group of investigators, before and after application of toluidine blue dye. The overall Kappa-value for the four observers' judgment of lesion vs. no lesion was 0.41 which can be interpreted as moderate agreement. Intra-observer agreement was calculated for two of the observers looking at photographs with a 10 months' time-gap, and the Kappa-values were 0.41 and 0.52. Positive and negative predictive values of the photographs were 82 and 81 % respectively. This study demonstrates relatively poor reliability of colposcopic photography. Some would argue that this makes colposcopic photography a low-quality method of evaluation and that forensic science should aim for higher standards because of its use in court. Others would argue that as long as the limitations of a scientific method are acknowledged then it is still eligible for use. The moderate agreement and accuracy stresses the need for quality control in the gynecological part of a rape examination. Colposcopic photography also provides a good option for supervision and teaching in an ethically difficult setting. It strengthens the legal rights for both victim and perpetrator.

An evaluation was conducted on the results of the Certified Safe Farm controlled intervention program on a wide range of occupational health and safety outcomes. This report focuses on the outcomes of personal protective equipment (PPE) usage among one cohort of 438 Iowa (owner-operator) farmers in the Certified Safe Farm study during a 5-year period from 2004 to 2008. Intervention farmers reported an 11% increase in regular respirator usage and a 23% increase in regular use of hearing protection relative to comparison groups. Furthermore, it was revealed that personal factors such as smoking and low self-assessment of health status are associated with lower usage of PPE. The authors provide evidence that multiple modalities of intervention are more likely to affect safe behavior changes in the owner-operator farming population compared with single modality interventions. Further, farmers reported that personal factors such as smoking history and low self-assessment of health status are associated with lower usage of PPE.

Unlabelled: This study aims to estimate bisphosphonate effectiveness by comparing fracture incidence over time on therapy in glucocorticoid-induced osteoporosis (GIO). From this observational study, alendronate and risedronate decreased clinical vertebral and nonvertebral fractures over time. The effectiveness of each bisphosphonate is consistent with their efficacies demonstrated on surrogate markers in randomized controlled trials (RCTs)., Introduction: This study aims to estimate bisphosphonate effectiveness by comparing fracture incidence over time on therapy with fracture incidence during a short period after starting a therapy., Methods: The study population was a subgroup of a larger cohort study comprising two cohorts of women aged ≥65 years, prescribed with alendronate or risedronate. Within the two study cohorts, 11,007 women were identified as having received glucocorticoids. Within each cohort, the baseline incidence of clinical fractures at nonvertebral and vertebral sites was defined by the initial 3-month period after starting therapy. Relative to these baseline data, we then compared the fracture incidence during the subsequent 12 months on therapy., Results: The baseline incidence of clinical nonvertebral and vertebral fractures was similar in the alendronate cohort (5.22 and 5.79/100 person-years, respectively) and in the risedronate cohort (5.51 and 5.68/100 person-years, respectively). Relative to the baseline incidence, fracture incidence was significantly lower in the subsequent 12 months in both cohorts of alendronate (33 % lower at nonvertebral sites and 59 % at vertebral sites) and risedronate (28 % lower at nonvertebral sites and 54 % at vertebral sites)., Conclusion: From this observational study not designed to compare drugs, both alendronate and risedronate decreased clinical vertebral and nonvertebral fractures over time. The reductions observed in fracture incidence, within each cohort, suggest that the effectiveness of each bisphosphonate in clinical practice is consistent with their efficacies demonstrated on surrogate markers in randomized controlled trials.

Objective: Prior observational studies have shown an association between bisphosphonate adherence and fewer fractures. It is unclear if such studies reflect pharmacologic benefits or behavioral attributes, i.e., the healthy adherer effect. Our objective was to examine the association of therapy adherence and fracture risk among patients initiating therapies hypothesized to be favorable, unfavorable, or neutral toward fracture risk, in order to evaluate for a healthy adherer effect., Methods: In this observational study, we identified patients within Medicare 2006-2009 data who initiated any of 3 medication groups within 9 months after an osteoporotic fracture as follows: 1) oral bisphosphonates (n = 2,507), 2) selective serotonin reuptake inhibitors (SSRIs; n = 2,420), or 3) angiotensin-converting enzyme (ACE) inhibitor or calcium-channel blocker (CCB; n = 2,178). Cox regression analysis, adjusting for covariates, was used to compare fracture rates at the hip and major osteoporotic fracture sites (including hip, clinical vertebral, humerus, and wrist) during followup, comparing patients with high adherence versus low adherence within each medication group., Results: There were few baseline differences between those who had high adherence versus lower adherence. High adherence with bisphosphonates decreased fracture risk at both hip (hazard ratio [HR] 0.53, 95% confidence interval [95% CI] 0.32-0.96) and major fracture sites (HR 0.61, 95% CI 0.45-0.80). High adherence with SSRIs suggested increased fracture risk at both hip (HR 1.58, 95% CI 0.97-2.57) and major fracture sites (HR 1.32, 95% CI 0.96-1.83). High adherence with ACE inhibitors/CCBs was neutral toward fracture risk at both hip (HR 1.27, 95% CI 0.67-2.41) and major fracture sites (HR 1.00, 95% CI 0.67-1.49)., Conclusion: In this observational cohort of older individuals, the association between medication adherence and fracture risk differed by medication exposure, suggesting a limited role for the healthy adherer effect in observational studies of osteoporosis medications., (Copyright © 2012 by the American College of Rheumatology.)

Cardiac arrest may occur while persons are being kept in hobble restraint. It has been suggested that asphyxia caused by the restraint position, so-called restraint asphyxia, is the cause, but experimental evidence has not confirmed this theory. Some of the sudden deaths are associated with excited delirium syndrome (EDS), an acute condition characterized by a hyperactive, combative behaviour in individuals, who are influenced by psychoactive drugs or suffer from psychiatric illness. Autopsy findings fail to explain this type of deaths. The pathophysiology of EDS is complex and poorly understood. Sensibilisation of the heart by a hyperadrenergic autonomous dysfunction, metabolic acidosis and hyperthermia offer possible mechanisms.

Introduction: In cases of sexual assault, the finding of semen can provide crucial evidence. The presence of spermatozoa serves as proof of a sexual act and may give the identity of the alleged perpetrator through DNA-profiling. In most western countries, there are guidelines for standardized examinations of sexual assault victims. For an objective evaluation of the findings, substantial knowledge of aspects regarding consensual sexual intercourse is crucial. The aim of this study was to examine detection frequencies and genital sampling sites of spermatozoa following consensual sexual intercourse., Methods: In a prospective setting, 60 women underwent forensic examination following consensual sexual intercourse. Specimens were obtained from the external genitalia, the posterior fornix and the cervical canal, and examined using the Papanicolau stain and standard light microscopy., Results: We found that 88% of possible cases were positive for spermatozoa. The posterior fornix was significantly better than the other sites for detection of spermatozoa and the number of spermatozoa decreased significantly over time. In a large sub-group of women who reported that no intra-vaginal ejaculation had taken place during their latest intercourse, a significant number (14%) had spermatozoa in the vagina., Conclusion: Spermatozoa were best recovered from the posterior fornix, but spermatozoa were also present on swabs taken from the external genitalia. Detection of spermatozoa is thus possible in cases where a speculum examination is denied., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Background: We previously reported significant associations between genetic variants in insulin receptor substrate 1 (IRS1) and breast cancer risk in women carrying BRCA1 mutations. The objectives of this study were to investigate whether the IRS1 variants modified ovarian cancer risk and were associated with breast cancer risk in a larger cohort of BRCA1 and BRCA2 mutation carriers., Methods: IRS1 rs1801123, rs1330645, and rs1801278 were genotyped in samples from 36 centers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Data were analyzed by a retrospective cohort approach modeling the associations with breast and ovarian cancer risks simultaneously. Analyses were stratified by BRCA1 and BRCA2 status and mutation class in BRCA1 carriers., Results: Rs1801278 (Gly972Arg) was associated with ovarian cancer risk for both BRCA1 (HR, 1.43; 95% confidence interval (CI), 1.06-1.92; P = 0.019) and BRCA2 mutation carriers (HR, 2.21; 95% CI, 1.39-3.52, P = 0.0008). For BRCA1 mutation carriers, the breast cancer risk was higher in carriers with class II mutations than class I mutations (class II HR, 1.86; 95% CI, 1.28-2.70; class I HR, 0.86; 95%CI, 0.69-1.09; P(difference), 0.0006). Rs13306465 was associated with ovarian cancer risk in BRCA1 class II mutation carriers (HR, 2.42; P = 0.03)., Conclusion: The IRS1 Gly972Arg single-nucleotide polymorphism, which affects insulin-like growth factor and insulin signaling, modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers and breast cancer risk in BRCA1 class II mutation carriers., Impact: These findings may prove useful for risk prediction for breast and ovarian cancers in BRCA1 and BRCA2 mutation carriers., (©2012 AACR.)

Objective: The purpose of this study was to make a normative description of the nature and duration of genital lesions sustained during consensual sexual intercourse, using the three most commonly used techniques; visualisation using the naked eye, colposcopy and toluidine blue dye followed by colposcopy., Methods: Ninety eight women were examined within 48 h of consensual sexual intercourse. Fifty of the women were examined twice again within the following 7 days of sexual abstinence after the first examination., Results: The participants had a median age of 22.4 years and 88% were nulliparous. Lesions were frequent; 34% seen with the naked eye, 49% seen with colposcopy and 52% seen with toluidine blue dye and subsequent colposcopy. The lesions lasted for several days; the median survival times for lacerations were 24, 40 and 80 h, respectively., Conclusions: The legal implications of these findings are that genital lesions by themselves do not corroborate a rape complaint. Genital lesions may, however, corroborate specific details of a case and should be documented as carefully as any other lesion in rape complaints., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Background: Inherited disease may be causative in many young sudden unexpected death cases. Autopsy is essential in the counselling of the bereaved, as the family of the victim may be at risk too. In a nationwide setting operating under the same set of laws, we hypothesized that regional differences exist in the investigation of young persons dying suddenly and unexpectedly., Methods and Results: All deaths in persons aged 1-35 years in Denmark in 2000-2006 were included. Death certificates were read independently by two physicians. External examination as well as autopsy status was retrieved. Significant regional differences were found regarding external examinations and autopsy frequencies. Ratios of conducted external examinations varied between 63% and 93% (p = 0.004). Autopsy ratios varied between 60% and 88% (p = 0.001). In urban areas, external examinations and autopsies were more often conducted than in rural areas. In East Denmark, there were more external examinations resulting in a forensic autopsy, and there was a higher overall autopsy rate compared to West Denmark., Conclusion: Despite operating under the same set of laws, we document significant regional differences in forensic investigations of young persons suffering a sudden unexpected death. This is probably not unique for Denmark although no data exist to confirm that. The results are worrying and call for a revision of the way these deaths are handled. Mandatory autopsy in sudden unexpected death in young persons is warranted as a thorough investigation of the death may help the clinician in guidance of the relatives in relation to hereditary diseases.