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Background: Prescription opioids have contributed to the rise in opioid‐related overdoses and deaths. The presence of opioids within households may increase the risk of overdose among family members who were not prescribed an opioid themselves. Larger quantities of opioids may further increase risk. Objectives: To determine the risk of opioid overdose among individuals who were not prescribed an opioid but were exposed to opioids prescribed to other family members in the household, and evaluate the risk in relation to the total morphine milligram equivalents (MMEs) present in the household. Methods: We conducted a cohort study using a large database of commercial insurance claims from 2001 to 2021. For inclusion in the cohort, we identified individuals not prescribed an opioid in the prior 90 days from households with two or more family members, and determined the total MMEs prescribed to other family members. Individuals were stratified into monthly enrollment strata defined by household opioid exposure and other confounders. A generalized linear model was used to estimate incidence rate ratios (IRRs) for overdose. Results: Overall, the incidence of overdose among enrollees in households where a family member was prescribed an opioid was 1.73 (95% confidence interval [CI]: 1.67–1.78) times greater than households without opioid prescriptions. The risk of overdose increased continuously with the level of potential MMEs in the household from an IRR of 1.23 (95% CI: 1.16–1.32) for 1–100 MMEs to 4.67 (95% CI: 4.18–5.22) for >12,000 MMEs. The risk of overdose associated with household opioid exposure was greatest for ages 1–2 years (IRR: 3.46 [95% CI: 2.98–4.01]) and 3–5 years (IRR: 3.31 [95% CI: 2.75–3.99]). Conclusions: The presence of opioids in a household significantly increases the risk of overdose among other family members who were not prescribed an opioid. Higher levels of MMEs, either in terms of opioid strength or quantity, were associated with increased levels of risk. Risk estimates may reflect accidental poisonings among younger family members. [ABSTRACT FROM AUTHOR]

Sponges occur across diverse marine biomes and host internal microbial communities that can provide critical ecological functions. While strong patterns of host specificity have been observed consistently in sponge microbiomes, the precise ecological relationships between hosts and their symbiotic microbial communities remain to be fully delineated. In the current study, we investigate the relative roles of host population genetics and biogeography in structuring the microbial communities hosted by the excavating sponge Cliona delitrix. A total of 53 samples, previously used to demarcate the population genetic structure of C. delitrix, were selected from two locations in the Caribbean Sea and from eight locations across the reefs of Florida and the Bahamas. Microbial community diversity and composition were measured using Illumina‐based high‐throughput sequencing of the 16S rRNA V4 region and related to host population structure and geographic distribution. Most operational taxonomic units (OTUs) specific to Cliona delitrix microbiomes were rare, while other OTUs were shared with congeneric hosts. Across a large regional scale (>1,000 km), geographic distance was associated with considerable variability of the sponge microbiome, suggesting a distance–decay relationship, but little impact over smaller spatial scales (<300 km) was observed. Host population structure had a moderate effect on the structure of these microbial communities, regardless of geographic distance. These results support the interplay between geographic, environmental, and host factors as forces determining the community structure of microbiomes associated with C. delitrix. Moreover, these data suggest that the mechanisms of host regulation can be observed at the population genetic scale, prior to the onset of speciation. [ABSTRACT FROM AUTHOR]

Mesoscale oceanic features such as eddies generate considerable environmental heterogeneity within the pelagic oceans, but their transient nature makes it difficult to identify both their spatial and temporal extent and their effects on the distribution of pelagic fauna. Simplifying these complex features using a biologically meaningful classification system will likely be a useful first step in understanding the extent of their influence in structuring openocean ecosystems. In this study, we present a tool to classify the pelagic environment in the Gulf of Mexico using seasurface height and temperatureatdepth data from the 1/25° GOM HYbrid Coordinate Ocean Model (HYCOM). Three "water types" were identified: Loop Currentorigin water (LCOW), Gulf common water (CW), and mixed (MIX) water, where the latter represents an intermediate state during the degradation of LCOW to CW. The HYCOMderived classifications were validated against in situ CTD data and microbial samples collected through 2015–2016 by the Deep Pelagic Nekton Dynamics of the Gulf of Mexico (DEEPEND) consortium. The validation data comprised classifications derived from both temperaturedepth (TD) and temperaturesalinity (TS) profiles and from microbial community analyses from the surface to mesopelagic depths. The HYCOM classifications produced an overall agreement rate of 77% with the TS/TD classifications, and 79% with the microbial classifications. With applicability across a wide range of spatial and temporal scales, we believe that the system provides a useful, complementary tool for biological oceanographers and resource managers interested in better understanding the effects of major mesoscale features on the pelagic biota. [ABSTRACT FROM AUTHOR]

This study used Monte Carlo simulations to examine the ability of the two-stage least squares (2SLS) estimator and two-stage residual inclusion (2SRI) estimators with varying forms of residuals to estimate the local average and population average treatment effect parameters in models with binary outcome, endogenous binary treatment, and single binary instrument. The rarity of the outcome and the treatment was varied across simulation scenarios. Results showed that 2SLS generated consistent estimates of the local average treatment effects (LATE) and biased estimates of the average treatment effects (ATE) across all scenarios. 2SRI approaches, in general, produced biased estimates of both LATE and ATE under all scenarios. 2SRI using generalized residuals minimized the bias in ATE estimates. Use of 2SLS and 2SRI is illustrated in an empirical application estimating the effects of long-term care insurance on a variety of binary health care utilization outcomes among the near-elderly using the Health and Retirement Study. [ABSTRACT FROM AUTHOR]

Abstract: Background: Several environmental and lifestyle factors have been associated with multiple sclerosis (MS) risk, including some pharmacological treatments. We systematically reviewed the literature on prescription drug exposure and MS risk. Methods: Six databases were searched for original observational studies reporting drug exposure and MS risk published before 2017. Results: Thirteen articles fulfilled inclusion criteria. Exposure to neither amiloride nor valproic acid was associated with MS (adjusted hazard ratio (adj.HR = 1.34;95% CI:0.81–2.20; adj.HR = 1.30;95%CI:0.44–3.80, respectively). Four studies explored oral contraceptive exposure and reported no association with MS; while a single study found an increased risk (odds ratio [adj.OR] = 1.52;95%CI:1.21–1.91). While penicillin exposure was associated with reduced risk of developing MS (adj.OR = 0.5;95%CI:0.3–0.9), a later study observed an elevated risk for penicillin (adj.OR = 1.21;95%CI:1.10–1.27) and all antibiotics (adj.OR = 1.41;95%CI:1.29–1.53), which was potentially attributed to underlying infection. Anti‐tumor necrosis factor‐alpha (TNFα) was not associated with MS risk in persons with inflammatory bowel disease (standard morbidity ratio = 4.2;95%CI:0.1–23.0) and arthritis (standardized incidence ratio = 1.38;95%CI:0.69–2.77); however, men exposed to anti‐TNFα who also had arthritis and individuals with ankylosing spondylitis were at an increased risk (standardized incidence ratios = 3.91;95%CI:1.47–10.42 and 3.48;95%CI:1.45–8.37, respectively). A reduced risk of MS was observed with exposure to the beta2‐adrenergic agonist fenoterol (adj.OR = 0.58;95%CI:0.45–0.76), and the sedating histamine 1‐receptor antagonists (adj.OR = 0.2;95%CI:0.1–0.8), but not the non‐sedating equivalent (adj.OR = 0.8;95%CI:0.4–1.6). Conclusions: The suggestion that some drugs may prevent MS is intriguing and warrants further study. In addition, further pharmacovigilance is needed to assess the safety of anti‐TNFα drugs in specific populations in the context of MS risk. [ABSTRACT FROM AUTHOR]

Objective: To examine the settings of simulation evidence supporting use of nonlinear two-stage residual inclusion (2SRI) instrumental variable (IV) methods for estimating average treatment effects (ATE) using observational data and investigate potential bias of 2SRI across alternative scenarios of essential heterogeneity and uniqueness of marginal patients.Study Design: Potential bias of linear and nonlinear IV methods for ATE and local average treatment effects (LATE) is assessed using simulation models with a binary outcome and binary endogenous treatment across settings varying by the relationship between treatment effectiveness and treatment choice.Principal Findings: Results show that nonlinear 2SRI models produce estimates of ATE and LATE that are substantially biased when the relationships between treatment and outcome for marginal patients are unique from relationships for the full population. Bias of linear IV estimates for LATE was low across all scenarios.Conclusions: Researchers are increasingly opting for nonlinear 2SRI to estimate treatment effects in models with binary and otherwise inherently nonlinear dependent variables, believing that it produces generally unbiased and consistent estimates. This research shows that positive properties of nonlinear 2SRI rely on assumptions about the relationships between treatment effect heterogeneity and choice. [ABSTRACT FROM AUTHOR]

Case report An 8-year-old 40.8-kg intact male German Shepherd Dog was evaluated for bilateral antebrachial fractures. Radiographs revealed osteopenia and comminuted proximal diaphyseal fractures of the left radius and ulna, and proximal articular fracture of the right ulna. A dual energy X-ray absorptiometry scan confirmed decreased bone mineral density. Bone mineral analysis collected at the time of definitive surgical repair demonstrated high lead concentration. Analysis further demonstrated normal bone calcium and phosphorus concentrations. Serum lead concentration was normal. The left radial and ulnar fractures were surgically stabilised with an external fixator. The right ulnar fracture was splinted. The left antebrachial fractures were palpably unstable at 12 weeks after surgery. Moderate callus formation and incomplete bone union were present at 17 weeks postoperatively. The dog was re-presented 15 months later for right metacarpal and left metatarsal fractures, which were managed conservatively. Complete bone union of the right radial and ulnar fractures was not present at that time. Conclusion Excessive lead accumulation in bone should be considered as a differential diagnosis for increased susceptibility to pathologic fracture and delayed fracture healing in dogs. [ABSTRACT FROM AUTHOR]

ABSTRACT A recently described case of putative early tertiary syphilis in a young adult male from 6th century Anglo-Saxon England exhibits a distinctive endocranial pathology. A case-control study using both clinical and archaeological materials was performed to investigate a possible association of the pathology with syphilis. Scanning electron microscopy and microcomputed tomography were used to image the syphilitic case and normal cranial material. Although the pathology does seem to have an association with syphilis (OR = 13.14), the sample size is small, and the authors caution against overinterpretation of the results. The study confirms observations by other authors suggesting the lesion has some association with a range of pathological conditions. Any association with syphilis seems to be restricted to the early tertiary stages and is possibly absent in the later stages of the disease. The morphological differences present in the samples observed by scanning electron microscopy and microcomputed tomography illustrate the abnormal nature of the vascularity within the syphilitic cranium. The widespread presence of similar lesions within other tubular bones leads the authors to propose hypothesis that unresolved angiogenesis is the underlying mechanism behind the skeletal changes in tertiary syphilis. This angiogenic model accounts for several diverse characteristics in the progression of skeletal disease resulting from infection by spirochetes of the Treponema pallidum family. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The article examines the methodologies and philosophies underlying modern economics. A history of modern economics is provided, beginning with the rise of capitalism during the Industrial Revolution. The author focuses upon the postulations of the English philosopher Jeremy Bentham, particularly evaluating how his theory of utilitarianism applies to macroeconomics. A correlation between the development of capitalism and the implementation of parliamentary democracy is examined, and the author criticizes the tenets of demand-based economics.

To analyse the performance of candidates in a Canadian national mock-examination for final-year urology residents with respect to North American speciality examinations in urology. In 1997 the Queen's Urology Examination Skills Training Program (QUEST) was established as an annual national mock examination for final-year Canadian urology residents. It consists of a short answer question component and an objective structured clinical examination. During the 5-year period (1997–2001), 91 final-year residents from all 11 Canadian urology residency-training programmes participated in QUEST and the Royal College of Physicians and Surgeons of Canada certifying examinations (RCPSCE); 43 (47%) of candidates also attempted the American Board of Urology part 1 qualifying examinations (ABU 1). Performance on QUEST was correlated with the RCPSCE and ABU 1 in a blinded fashion after submitting QUEST scores to governing bodies. Thresholds were determined to help to predict a candidate's performance on the RCPSCE and ABU 1, based on QUEST scores. There was a moderately close correlation between overall QUEST and RCPSCE performance ( r = 0.68, P < 0.001) and a moderate correlation between overall QUEST and ABU 1 performance ( r = 0.42, P = 0.005). For the following QUEST scores, the probability of success on the RCPSCE was: <65%, 67% pass; 66–75%, 80% pass; > 75%, 100% pass ( P = 0.002). For ABU 1, QUEST overall score of 80% gave a 69% probability of scoring ≥ 70% on ABU 1 ( P = 0.003). QUEST is a moderate predictor of performance on speciality examinations in urology. We consider that the time, effort and expense to maintain QUEST are justified. [ABSTRACT FROM AUTHOR]

Non-steroidal anti-inflammatory drugs (NSAIDs) have been associated with reduced risk for Alzheimer's disease (AD) and selected NSAIDs racemates suppress β-amyloid (Aβ) accumulation in vivo and Aβ42 production in vitro. Clinical use of NSAIDs for preventing or treating AD has been hampered by dose-limiting toxicity believed to be due to cyclooxygenase (COX)-inhibition that is reportedly not essential for selective Aβ42 reduction. Profens have racemates and R-enantiomers were supposed to be inactive forms. Here we demonstrate that R-ibuprofen and R-flurbiprofen, with poor COX-inhibiting activity, reduce Aβ42 production by human cells. Although these R-enantiomers inhibit nuclear factorκB (NF-κB) activation and NF-κB can selectively regulate Aβ42, Aβ42 reduction is not mediated by inhibition of NF-κB activation. Because of its efficacy at lowering Aβ42 production and low toxicity profile, R-flurbiprofen is a strong candidate for clinical development. [ABSTRACT FROM AUTHOR]

Abstract: The apolipoprotein E (ApoE) ε4 allele is a major risk factor for neurodegenerative conditions, including Alzheimer's disease. A role for ApoE is implicated in regeneration of synaptic circuitry after neural injury. In the in vitro mouse organotypic hippocampal slice culture system, we previously showed that cultures derived from ApoE-knockout mice are defective in mossy fiber sprouting into the dentate gyrus molecular layer. This sprouting defect was rescued in cultures from transgenic mice expressing ApoE3 under the control of the human promoter and in ApoE-knockout cultures treated with ApoE3-conditioned media. Although the ApoE3 transgene fully restored sprouting, ApoE4 restored sprouting to only 58% of ApoE3 levels. These data indicate that ApoE isoform-specific effects on neuroregeneration may contribute to its genetic risk for Alzheimer's disease. [ABSTRACT FROM AUTHOR]

The article presents information on neuropathology and clinical practice in mental handicap. Autopsies are systematically arranged in very few hospitals for the mentally handicapped despite the opportunities they provide for comparing clinical observation with post-mortem changes. Aetiology in mental handicap is almost invariably multifactorial. The initial insult, which may be environmental or genetic, can be modified by later factors affecting development. These influences may leave their imprints on the brain and central nervous system, giving clues as to the superimposition of damaging or ameliorating effects. Such findings may have important implications for management and treatment, but very little has been done to explore these causal links so far.

Autopsies were carried out on 60 mentally handicapped patients and the brain was examined in detail in all cases. The clinical records were studied and correlated with the pathological findings. A variety of pathological changes were found in the central nervous system, and there was a high incidence of microcephaly and gross abnormalities among the patients with epilepsy and neurological dysfunction. The incidence of Alzheimer's disease was very high among patients with Down's syndrome, but in those patients without Down's syndrome, the incidence appeared to be much the same as in the general population. The most common cause of death was respiratory disease, followed by cardiovascular disease. There was a high incidence of volvulus among the group with epilepsy. The findings are discussed, and reference made to the long-term care of the mentally handicapped. The study demonstrates the importance of the autopsy in terms of furthering knowledge in the field of mental handicap. [ABSTRACT FROM AUTHOR]

A reprint of the article "The Essentials of Socialization," by G. D. H. Cole, which appeared in the July 1931 issue, is presented. Topics include methods for a transition from capitalism to socialism, the introduction of state ownership of transportation services in Great Britain in relation to the Railways Act of 1921, and the fixing of interest rates.