How well can U.S. military veterans' suicidal ideation be predicted from static and change-based indicators of their psychosocial well-being as they adapt to civilian life?

BACKGROUND: Identifying predictors of suicidal ideation (SI) is important to inform suicide prevention efforts, particularly among high-risk populations like military veterans. Although many studies have examined the contribution of psychopathology to veterans' SI, fewer studies have examined whether experiencing good psychosocial well-being with regard to multiple aspects of life can protect veterans from SI or evaluated whether SI risk prediction can be enhanced by considering change in life circumstances along with static factors. METHODS: The study drew from a longitudinal population-based sample of 7141 U.S. veterans assessed throughout the first three years after leaving military service. Machine learning methods (cross-validated random forests) were applied to examine the predictive utility of static and change-based well-being indicators to veterans' SI, as compared to psychopathology predictors. RESULTS: Although psychopathology models performed better, the full set of well-being predictors demonstrated acceptable discrimination in predicting new-onset SI and accounted for approximately two-thirds of cases of SI in the top strata (quintile) of predicted risk. Greater engagement in health promoting behavior and social well-being were most important in predicting reduced SI risk, with several change-based predictors of SI identified but stronger associations observed for static as compared to change-based indicator sets as a whole. CONCLUSIONS: Findings support the value of considering veterans' broader well-being in identifying individuals at risk for suicidal ideation and suggest the possibility that well-being promotion efforts may be useful in reducing suicide risk. Findings also highlight the need for additional attention to change-based predictors to better understand their potential value in identifying individuals at risk for SI.

Dry eye symptoms and signs in United States Gulf War era veterans with myalgic encephalomyelitis/chronic fatigue syndrome.

BACKGROUND: To examine ocular symptoms and signs of veterans with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) diagnosis, ME/CFS symptoms, and controls. METHODS: This was a prospective, cross-sectional study of 124 South Florida veterans in active duty during the Gulf War era. Participants were recruited at an ophthalmology clinic at the Miami Veterans Affairs Hospital and evaluated for a diagnosis of ME/CFS, or symptoms of ME/CFS (intermediate fatigue, IF) using the Canadian Consensus criteria. Ocular symptoms were assessed via standardised questionnaires and signs via comprehensive slit lamp examination. Inflammatory blood markers were analysed and compared across groups. RESULTS: Mean age was 55.1 ± 4.7 years, 88.7% identified as male, 58.1% as White, and 39.5% as Hispanic. Ocular symptoms were more severe in the ME/CFS (n = 32) and IF (n = 48) groups compared to controls (n = 44) across dry eye (DE; Ocular Surface Disease Index [OSDI]: 48.9 ± 22.3 vs. 38.8 ± 23.3 vs. 19.1 ± 17.8, p < 0.001; 5 item Dry Eye Questionnaire [DEQ-5]: 10.8 ± 3.9 vs. 10.0 ± 4.6 vs. 6.6 ± 4.2, p < 0.001) and pain-specific questionnaires (Numerical Rating Scale 1-10 [NRS] right now: 2.4 ± 2.8 vs. 2.4 ± 2.9 vs 0.9 ± 1.5; p = 0.007; Neuropathic Pain Symptom Inventory modified for the Eye [NPSI-E]: 23.0 ± 18.6 vs. 19.8 ± 19.1 vs. 6.5 ± 9.0, p < 0.001). Ocular surface parameters and blood markers of inflammation were generally similar across groups. CONCLUSION: Individuals with ME/CFS report increased ocular pain but similar DE signs, suggesting that mechanisms beyond the ocular surface contribute to symptoms.

Arthroscopic Anatomic Anterior Cruciate Ligament Primary Repair Restores Anterior Tibial Translation Intraoperatively at Time Zero With No Additional Effect of Suture Augmentation.

PURPOSE: To intraoperatively evaluate the ability of anterior cruciate ligament (ACL) primary repair (ACLPR) to restore anterior tibial translation (ATT) at time zero and to assess the influence of additional suture augmentation (SA) on ATT. METHODS: Patients with proximal ACL tears undergoing arthroscopic ACLPR with dual-suture anchor fixation were included in this time-zero clinical study. Laxity measurements were taken with a digital arthrometer to evaluate ATT stability preoperatively in the office (T0) as a standardized diagnostic tool, preoperatively under anesthesia (T1), at time zero intraoperatively after ACLPR but prior to SA fixation (T2), and after SA fixation (T3). RESULTS: A total of 27 patients (mean age ± standard deviation [SD], 35.1 ± 12.0 years) with proximal ACL tears and significant preoperative (T0) ATT side-to-side differences (SSDs) (mean ± SD, 4.1 ± 1.5 mm) were evaluated. ACLPR was shown to restore ATT SSD at time zero (mean ± SD, 0.2 ± 1.1 mm) given that a significant reduction in ATT SSD (mean difference ± standard error, -4.7 ± 0.21 mm; P < .001) was achieved when comparing preoperative and intraoperative measurements after separate refixation of both ACL bundles with suture anchors. Additional SA fixation did not further decrease ATT when comparing measurements of the ipsilateral leg after ACL refixation and after SA fixation (mean difference ± SD, 0.03 ± 0.22 mm; P = .496). CONCLUSIONS: ACLPR with dual-suture anchor fixation restores time-zero ATT laxity in adults with proximal ACL tears. Additional SA fixation in full knee extension does not further decrease ATT. CLINICAL RELEVANCE: This study provides important information about the effectiveness of ACLPR in restoring ATT. SA with the knee fixed in full knee extension does not further decrease ATT; therefore, augmentation may not lead to overconstraint of the knee or stress shielding of the repaired ACL.

Anterior cruciate ligament primary repair revision rates are increased in skeletally mature patients under the age of 21 compared to reconstruction, while adults (>21 years) show no significant difference: A systematic review and meta-analysis.

PURPOSE: To evaluate the impact of age as a risk factor on the revision rates of anterior cruciate ligament (ACL) primary repair (ACLPR), dynamic intraligamentary stabilization (DIS) and bridge-enhanced ACL restoration (BEAR) compared to ACL reconstruction (ACLR). METHODS: A systematic literature search was performed for comparative studies comparing outcomes for ACLPR, DIS or BEAR to ACLR. A random-effects meta-analysis was performed to assess nondifferentiated and age-differentiated (skeletally mature patients ≤21 and >21 years) ACL revision and reoperation risk, as well as results for subjective outcomes. Methodological study quality was assessed using the Risk of Bias Tool 2.0c and Methodological Index for Nonrandomized Studies tools. RESULTS: A total of 12 studies (n = 1277) were included. ACLR demonstrated a lower nonage-stratified revision risk at 2 years versus ACLPR, DIS and BEAR, but a similar revision risk at 5 years when compared to DIS. However, an age-stratified analysis demonstrated a significantly increased ACLPR revision risk as compared to ACLR in skeletally mature patients ≤21 years of age (risk ratios [RR], 6.33; 95% confidence interval [CI], 1.18-33.87, p = 0.03), while adults (>21 years) showed no significant difference between groups (RR, 1.48; 95% CI, 0.25-8.91, n.s.). Furthermore, DIS reoperation rates were significantly higher than respective ACLR rates (RR, 2.22; 95% CI, 1.35-3.65, p = 0.002), whereas BEAR (RR, 1.07; 95% CI, 0.41-2.75, n.s.) and ACLPR (RR, 0.81; 95% CI, 0.21-3.09, n.s.) showed no differences. IKDC scores were equivalent for all techniques. However, ACLPR exhibited significantly better FJS (mean difference, 11.93; 95% CI, 6.36-17.51, p < 0.0001) and Knee injury and Osteoarthritis Outcome Score Symptoms (mean difference, 3.01; 95% CI, 0.42-5.60, p = 0.02), along with a lower Tegner activity reduction. CONCLUSIONS: ACLPR in skeletally mature patients ≤21 years of age is associated with up to a six-fold risk increase for ACL revision surgery compared to ACLR; however, adults (>21 years) present no significant difference. Based on the current data, age emerges as a crucial risk factor and should be considered when deciding on the appropriate treatment option in proximal ACL tears. LEVEL OF EVIDENCE: Level III.

Associations of vulnerability to stressful life events with suicide attempts after active duty among high-risk soldiers: results from the Study to Assess Risk and Resilience in Servicemembers-longitudinal study (STARRS-LS).

BACKGROUND: The transition from military service to civilian life is a high-risk period for suicide attempts (SAs). Although stressful life events (SLEs) faced by transitioning soldiers are thought to be implicated, systematic prospective evidence is lacking. METHODS: Participants in the Army Study to Assess Risk and Resilience in Servicemembers (STARRS) completed baseline self-report surveys while on active duty in 2011-2014. Two self-report follow-up Longitudinal Surveys (LS1: 2016-2018; LS2: 2018-2019) were subsequently administered to probability subsamples of these baseline respondents. As detailed in a previous report, a SA risk index based on survey, administrative, and geospatial data collected before separation/deactivation identified 15% of the LS respondents who had separated/deactivated as being high-risk for self-reported post-separation/deactivation SAs. The current report presents an investigation of the extent to which self-reported SLEs occurring in the 12 months before each LS survey might have mediated/modified the association between this SA risk index and post-separation/deactivation SAs. RESULTS: The 15% of respondents identified as high-risk had a significantly elevated prevalence of some post-separation/deactivation SLEs. In addition, the associations of some SLEs with SAs were significantly stronger among predicted high-risk than lower-risk respondents. Demographic rate decomposition showed that 59.5% (s.e. = 10.2) of the overall association between the predicted high-risk index and subsequent SAs was linked to these SLEs. CONCLUSIONS: It might be possible to prevent a substantial proportion of post-separation/deactivation SAs by providing high-risk soldiers with targeted preventive interventions for exposure/vulnerability to commonly occurring SLEs.

Predicting suicide attempts among U.S. Army soldiers after leaving active duty using information available before leaving active duty: results from the Study to Assess Risk and Resilience in Servicemembers-Longitudinal Study (STARRS-LS).

Suicide risk is elevated among military service members who recently transitioned to civilian life. Identifying high-risk service members before this transition could facilitate provision of targeted preventive interventions. We investigated the feasibility of doing this by attempting to develop a prediction model for self-reported suicide attempts (SAs) after leaving or being released from active duty in the Study to Assess Risk and Resilience in Servicemembers-Longitudinal Study (STARRS-LS). This study included two self-report panel surveys (LS1: 2016-2018, LS2: 2018-2019) administered to respondents who previously participated while on active duty in one of three Army STARRS 2011-2014 baseline self-report surveys. We focus on respondents who left active duty >12 months before their LS survey (n = 8899). An ensemble machine learning model using predictors available prior to leaving active duty was developed in a 70% training sample and validated in a 30% test sample. The 12-month self-reported SA prevalence (SE) was 1.0% (0.1). Test sample AUC (SE) was 0.74 (0.06). The 15% of respondents with highest predicted risk included nearly two-thirds of 12-month SAs and over 80% of medically serious 12-month SAs. These results show that it is possible to identify soldiers at high post-transition self-report SA risk before the transition. Future model development is needed to examine prediction of SAs assessed by administrative data and using surveys administered closer to the time of leaving active duty.

Treating Combined Anterior Cruciate Ligament and Medial Collateral Ligament Injuries Operatively in the Acute Setting Is Potentially Advantageous.

Combined injury of the anterior cruciate ligament (ACL) and medial collateral ligament (MCL) remains among the most common knee injury patterns in orthopaedics. Optimal treatment of grade III MCL injuries is still debated, especially when combined with ACL injury. Most patients with these severe injuries are treated conservatively for at least 6 weeks to allow for MCL healing, followed by delayed ACL reconstruction. Although acute treatment of the MCL was common in the 1970s, postoperative stiffness was frequently reported. Moreover, studies of such treatment failed to show clinical benefits of surgical over conservative treatment, and the MCL exhibited intrinsic healing capacity, leading to the consensus that all MCL injuries are treated conservatively. The current delayed treatment algorithm for ACL-MCL injuries has several disadvantages. First, MCL healing may be incomplete, resulting in residual valgus laxity that places the ACL graft at greater risk of failure. Second, delayed treatment lengthens the overall rehabilitation period, thereby prolonging the presence of atrophy and delaying return to preinjury activity levels. Third, the initial healing period leaves the knee unstable for longer and risks further intra-articular damage. Acute simultaneous surgical treatment of both ligaments has the potential to avoid these shortcomings. This article will review the evolution of treatment of ACL-MCL injuries and explain how it shifted toward the current treatment algorithm. We will (1) discuss why the consensus shifted, (2) discuss the shortcomings of the current treatment plan, (3) discuss the potential advantages of acute simultaneous treatment, and (4) present an overview of the available literature.

A Comparison of Complication Rates in Wise Pattern Versus Vertical Breast Reduction.

BACKGROUND: Breast reduction has a well-chronicled history and remains a common reason for patients to seek plastic surgery consultation. The Wise pattern is the most common skin reduction pattern in the United States. Vertical pattern reduction is also widely used and offers the potential for decreased scar burden. Both patterns have been used with a variety of pedicles for preservation of the nipple areolar complex, which may also impact complication rate and patient satisfaction. There is a preponderance of literature on breast reduction surgery but limited comparative data on the safety profile of these patterns. The purpose of this article is to review the comparative literature, with emphasis on the overall risk of complications. METHODS: OVID and PubMed were used to query the literature for articles comparing complication rates in both Wise pattern and vertical breast reduction. Inclusion criteria were case series that encompassed both vertical and Wise pattern reductions and cited the rate of complications. Complications included in our analysis of total complication rate were as follows: hematoma, seroma, infection, dehiscence, fat necrosis, skin necrosis, and nipple areolar complex necrosis. We excluded standing cutaneous deformity as a complication. Articles that included oncoplastic breast reductions were also excluded. The primary analysis was an inverse variance-weighted random-effect meta-analysis of overall complication rate, with the association between the technique and overall complication rate quantified using odds ratios. RESULTS: Eight articles were identified that met inclusion criteria, representing 963 patients (525 Wise pattern and 438 vertical pattern). The overall complication rate pooled across the studies favored vertical pattern reduction, but the result was not definitive. CONCLUSIONS: Vertical pattern breast reduction can be done safely. Our statistical analysis found a trend toward decreased complications with vertical reductions, but did not reach statistical significance. Patients seeking breast reduction are a heterogeneous population with respect to breast size, degree of ptosis, body habitus, body mass index, comorbidities, and acceptance of scars. It remains important to individualize the approach to the patient and their needs. More quantitative, comparative data, especially from randomized controlled trials, would be useful to further evaluate the relative safety profiles of the 2 patterns.

A simplified approach for establishing estimable functions in fixed effect age-period-cohort multiple classification models.

Estimable functions play an important role in learning about certain aspects of the impact of ages, periods, and cohorts in age-period-cohort multiple classification (APCMC) models. The advantage of these estimates is that they are unbiased estimates of, for example, the deviations of age, period, and cohort effects from their linear trends, or changes in the linear trends of cohort effects within cohorts, or the residuals of fixed effect APCMC models. If the fixed effect APCMC model contains the relevant variables (is well specified), these estimable functions are unbiased estimates of functions of the parameters that generated the dependent variable data, even though the parameters that generated that data are not identified. I provide a simplified approach to establishing which functions are estimable in fixed effect APCMC models that provides an intuitive understanding of estimable functions by showing clearly and simply why they are estimable. This approach involves the partitioning of the age, period, and cohort effects into linear components and deviations from the linear components; the use of the "line of solutions"; and of the "extended null vector."

Better together: a reappraisal of heterotopic heart transplantation.

Heterotopic heart transplantation (HHT) is rare in the modern era. When used as a biologic left ventricular assist, HHT provides pulsatile flow, supports the left ventricle with a physiologic cardiac output, responds to humoral stimuli, and with modern immunosuppression may offer long-term untethered survival. This study was undertaken to compare survival of HHT with orthotopic heart transplantation (OHT) to assess its viability in the modern era. In the United Network for Organ Sharing database, from January 1999 to December 2020, there were 27691 bicaval OHT, 13836 biatrial OHT, 1271 total OHT, and 51 HHT with sufficient follow-up. Survival was analyzed using restricted mean survival time (RMST) through 4 years as the outcome. In the first 4 years after transplant, compared with HHT, differences in RMST were 0.1 years (99% CI: -0.4 to 0.5 years) for bicaval OHT, 0.0 years (99% CI: -0.4 to 0.5 years) for biatrial OHT, and 0.0 years (99% CI: -0.5 to 0.4 years) for total OHT. In this cohort, survival was indistinguishable between HHT and OHT recipients in the first four years. Thus, HHT might be a viable alternative to durable mechanical circulatory assist particularly with size mismatched grafts or for patients with refractory pulmonary hypertension.

Evidence for seasonal cycles in deep-sea fish abundances: A great migration in the deep SE Atlantic?

Animal migrations are of global ecological significance, providing mechanisms for the transport of nutrients and energy between distant locations. In much of the deep sea (>200 m water depth), the export of nutrients from the surface ocean provides a crucial but seasonally variable energy source to seafloor ecosystems. Seasonal faunal migrations have been hypothesized to occur on the deep seafloor as a result, but have not been documented. Here, we analyse a 7.5-year record of photographic data from the Deep-ocean Environmental Long-term Observatory Systems seafloor observatories to determine whether there was evidence of seasonal (intra-annual) migratory behaviours in a deep-sea fish assemblage on the West African margin and, if so, identify potential cues for the behaviour. Our findings demonstrate a correlation between intra-annual changes in demersal fish abundance at 1,400 m depth and satellite-derived estimates of primary production off the coast of Angola. Highest fish abundances were observed in late November with a smaller peak in June, occurring approximately 4 months after corresponding peaks in primary production. Observed changes in fish abundance occurred too rapidly to be explained by recruitment or mortality, and must therefore have a behavioural driver. Given the recurrent patterns observed, and the established importance of bottom-up trophic structuring in deep-sea ecosystems, we hypothesize that a large fraction of the fish assemblage may conduct seasonal migrations in this region, and propose seasonal variability in surface ocean primary production as a plausible cause. Such trophic control could lead to changes in the abundance of fishes across the seafloor by affecting secondary production of prey species and/or carrion availability for example. In summary, we present the first evidence for seasonally recurring patterns in deep-sea demersal fish abundances over a 7-year period, and demonstrate a previously unobserved level of dynamism in the deep sea, potentially mirroring the great migrations so well characterized in terrestrial systems.

As migrações dos animais são importantes para a ecologia global pois fornecem mecanismos para o transporte de nutrientes e energia entre diferentes locais. Em grande parte do oceano profundo (>200 m de profundidade), a exportação de nutrientes da superfície para os ecossistemas do fundo marinho é uma fonte de energia crucial, mas que varia entre estações. Consequentemente, calcula-se que ocorram migrações sazonais de animais no fundo marinho, mas tal nunca foi reportado. Neste estudo, nós analisamos dados fotográficos do observatório do fundo marinho DELOS colhidos ao longo de 7.5 anos, para determinar se existem indícios de comportamentos migratórios sazonais (intra-anuais) na comunidade de peixes de profundidade na costa oeste africana ao largo de Angola e, se se confirmar, tentar identificar o que desencadeia este comportamento. Os resultados obtidos mostram que há uma correlação entre as alterações intra-anuais da densidade de peixes demersais a 1,400 m de profundidade e as estimativas de produção primária obtidas por satélite. A densidade de peixes atinge o seu máximo no final de Novembro, com um pico menos acentuado em Junho, aproximadamente quatro meses após os respectivos picos de produção primária na superfície. As alterações na densidade de peixe ocorreram de uma forma tão rápida que não podem ser explicadas por recrutamento ou mortalidade, e como tal devem só podem ser geradas por uma alteração do comportamento. Dado a recorrência do padrão observado, e importância da estrutura trófica fundo-topo em ecossistemas do oceano profundo, nós colocamos a hipótese de que uma fracção grande da comunidade de peixes faz migrações sazonais nesta região, e propomos que a variação sazonal da produção primária na superfície esteja na sua origem. Este controlo trófico poderá levar a alterações na densidade de peixes no fundo marinho via, por exemplo, a produção secundária de presas e/ou disponibilidade de corpos em processo de decomposição. Resumindo, nós apresentamos aqui a primeira evidência de padrões sazonais recorrentes na densidade de peixes demersais de profundidade ao longo de um período de sete anos, e provamos existir um nível de dinamismo nunca dantes observado no oceano profundo, que poderá espelhar as grandes migrações comummente observadas em sistemas terrestres.

Patients Forget About Their Operated Knee More Following Arthroscopic Primary Repair of the Anterior Cruciate Ligament Than Following Reconstruction.

PURPOSE: To assess the extent to which patients forget their operative knee joint on a daily basis following arthroscopic primary repair as compared with reconstruction of the anterior cruciate ligament (ACL) at short- to mid-term follow-up. METHODS: For this retrospective study, all patients undergoing ACL surgery between May 2012 and May 2017 were identified. All patients were treated with the algorithm of undergoing arthroscopic primary repair for proximal tears and reconstruction for nonrepairable tears. Patients were contacted to complete the Forgotten Joint Score-12 questionnaire between 2 and 5 years following surgery. A greater score represents a more favorable outcome indicating the patient's ability to "forget" the joint in everyday life, whereas lower scores indicate a less-favorable outcome. Data were analyzed using independent t-tests and χ2 tests, and multiple linear regression analysis was performed to correct for potential confounders. RESULTS: Eighty-three patients completed the questionnaire (57%). Patients who underwent primary repair thought about their operated knee less when compared with those patients who underwent reconstruction (85.3 ± 14.2 vs 74.3 ± 23.3, P = .022). These differences were significantly greater in patients older than 30 years (85.3 ± 12.9 vs 62.6 ± 24.9, P = .007), male patients (85.0 ± 13.6 vs 72.5 ± 24.7, P = .037), and patients with a body mass index greater than 25 (85.9 ± 14.5 vs 64.7 ± 25.6, P = .009). After we corrected for potential confounders, the overall difference remained significant (P = .045). CONCLUSIONS: Based on the data in this study, patients undergoing arthroscopic primary ACL repair can expect to have less daily awareness of their operated knee at short- to mid-term follow-up as compared with patients undergoing ACL reconstruction. LEVEL OF EVIDENCE: Retrospective comparative study, level III.

A Random Forests Quantile Classifier for Class Imbalanced Data.

Extending previous work on quantile classifiers (q-classifiers) we propose the q*-classifier for the class imbalance problem. The classifier assigns a sample to the minority class if the minority class conditional probability exceeds 0 < q* < 1, where q* equals the unconditional probability of observing a minority class sample. The motivation for q*-classification stems from a density-based approach and leads to the useful property that the q*-classifier maximizes the sum of the true positive and true negative rates. Moreover, because the procedure can be equivalently expressed as a cost-weighted Bayes classifier, it also minimizes weighted risk. Because of this dual optimization, the q*-classifier can achieve near zero risk in imbalance problems, while simultaneously optimizing true positive and true negative rates. We use random forests to apply q*-classification. This new method which we call RFQ is shown to outperform or is competitive with existing techniques with respect to tt-mean performance and variable selection. Extensions to the multiclass imbalanced setting are also considered.

BODY CONDITION OF EASTERN BOX TURTLES (TERRAPENE CAROLINA CAROLINA) EVALUATED BY COMPUTED TOMOGRAPHY.

Conservation efforts determining the health status of individuals can aid in assessing population health and sustainability. Body condition was determined in 65 free-ranging Eastern box turtles (Terrapene carolina carolina) from four locations in Vermilion County, Illinois, in the months of May, July, and September 2014, 2015, and 2016 using computed tomography (CT). Physical examinations were performed to determine morphometric measurements, and CT scans measured body fat. Twenty-three linear models were constructed to determine which morphometric measurements best correlated to fat content. The top two models of body fat included a relationship between mass and carapace width. Fat increases as both mass and carapace width increase. CT, while impractical for daily use, improved on previous methods of measuring body condition and created a calculation that can be applied broadly to Eastern box turtles. By understanding how measurements of mass and carapace width correlate to body condition, practitioners, researchers, and conservationists can evaluate chelonians with increased confidence in the accuracy of their assessment.

Continuous glucose monitoring in pregnant women with type 1 diabetes (CONCEPTT): a multicentre international randomised controlled trial.

BACKGROUND: Pregnant women with type 1 diabetes are a high-risk population who are recommended to strive for optimal glucose control, but neonatal outcomes attributed to maternal hyperglycaemia remain suboptimal. Our aim was to examine the effectiveness of continuous glucose monitoring (CGM) on maternal glucose control and obstetric and neonatal health outcomes. METHODS: In this multicentre, open-label, randomised controlled trial, we recruited women aged 18-40 years with type 1 diabetes for a minimum of 12 months who were receiving intensive insulin therapy. Participants were pregnant (≤13 weeks and 6 days' gestation) or planning pregnancy from 31 hospitals in Canada, England, Scotland, Spain, Italy, Ireland, and the USA. We ran two trials in parallel for pregnant participants and for participants planning pregnancy. In both trials, participants were randomly assigned to either CGM in addition to capillary glucose monitoring or capillary glucose monitoring alone. Randomisation was stratified by insulin delivery (pump or injections) and baseline glycated haemoglobin (HbA1c). The primary outcome was change in HbA1c from randomisation to 34 weeks' gestation in pregnant women and to 24 weeks or conception in women planning pregnancy, and was assessed in all randomised participants with baseline assessments. Secondary outcomes included obstetric and neonatal health outcomes, assessed with all available data without imputation. This trial is registered with ClinicalTrials.gov, number NCT01788527. FINDINGS: Between March 25, 2013, and March 22, 2016, we randomly assigned 325 women (215 pregnant, 110 planning pregnancy) to capillary glucose monitoring with CGM (108 pregnant and 53 planning pregnancy) or without (107 pregnant and 57 planning pregnancy). We found a small difference in HbA1c in pregnant women using CGM (mean difference -0·19%; 95% CI -0·34 to -0·03; p=0·0207). Pregnant CGM users spent more time in target (68% vs 61%; p=0·0034) and less time hyperglycaemic (27% vs 32%; p=0·0279) than did pregnant control participants, with comparable severe hypoglycaemia episodes (18 CGM and 21 control) and time spent hypoglycaemic (3% vs 4%; p=0·10). Neonatal health outcomes were significantly improved, with lower incidence of large for gestational age (odds ratio 0·51, 95% CI 0·28 to 0·90; p=0·0210), fewer neonatal intensive care admissions lasting more than 24 h (0·48; 0·26 to 0·86; p=0·0157), fewer incidences of neonatal hypoglycaemia (0·45; 0·22 to 0·89; p=0·0250), and 1-day shorter length of hospital stay (p=0·0091). We found no apparent benefit of CGM in women planning pregnancy. Adverse events occurred in 51 (48%) of CGM participants and 43 (40%) of control participants in the pregnancy trial, and in 12 (27%) of CGM participants and 21 (37%) of control participants in the planning pregnancy trial. Serious adverse events occurred in 13 (6%) participants in the pregnancy trial (eight [7%] CGM, five [5%] control) and in three (3%) participants in the planning pregnancy trial (two [4%] CGM and one [2%] control). The most common adverse events were skin reactions occurring in 49 (48%) of 103 CGM participants and eight (8%) of 104 control participants during pregnancy and in 23 (44%) of 52 CGM participants and five (9%) of 57 control participants in the planning pregnancy trial. The most common serious adverse events were gastrointestinal (nausea and vomiting in four participants during pregnancy and three participants planning pregnancy). INTERPRETATION: Use of CGM during pregnancy in patients with type 1 diabetes is associated with improved neonatal outcomes, which are likely to be attributed to reduced exposure to maternal hyperglycaemia. CGM should be offered to all pregnant women with type 1 diabetes using intensive insulin therapy. This study is the first to indicate potential for improvements in non-glycaemic health outcomes from CGM use. FUNDING: Juvenile Diabetes Research Foundation, Canadian Clinical Trials Network, and National Institute for Health Research.

Detection of intra-cardiac thrombi and congestive heart failure in cats using computed tomographic angiography.

Arterial thromboembolism is a life-threatening condition in cats most commonly secondary to cardiac disease. Echocardiography is the reference standard to evaluate for presence of a thrombus. In humans, computed tomographic (CT) angiography is becoming widely used to detect left atrial thrombi precluding the use of sedation. The purpose of this prospective, controlled, methods comparison pilot study was threefold: (1) describe new CT angiography protocol used in awake cats with cardiac disease and congestive heart failure; (2) determine accuracy of continuous and dynamic acquisition CT angiography to identify and characterize cardiac thrombi from spontaneous echocardiographic contrast using transthoracic echocardiography as our reference standard; (3) identify known negative prognostic factors and comorbidities of the thorax that CT angiography may provide that complement or supersede echocardiographic examination. Fourteen cats with heart disease were recruited; 7 with thrombi and 7 with spontaneous echocardiographic contrast. Echocardiography and awake CT angiography were performed using a microdose of contrast. Six of 7 thrombi were identified on CT angiography as filling defects by at least one reviewer within the left auricle (n = 6) and right heart (n = 1). Highest sensitivity (71.4%) was in continuous phase and highest specificity (85.7%) was in dynamic studies with fair to moderate interobserver agreement (0.38 and 0.44). CT angiography identified prognostic cardiac information (left atrial enlargement, congestive heart failure, arterial thromboembolism) and comorbidities (suspected idiopathic pulmonary fibrosis, asthma). This study indicates CT angiography can readily identify cardiac thrombi, important prognostic information and comorbidities, and can be safely performed in cats with cardiac disease and congestive heart failure.

Mixed models, linear dependency, and identification in age-period-cohort models.

This paper examines the identification problem in age-period-cohort models that use either linear or categorically coded ages, periods, and cohorts or combinations of these parameterizations. These models are not identified using the traditional fixed effect regression model approach because of a linear dependency between the ages, periods, and cohorts. However, these models can be identified if the researcher introduces a single just identifying constraint on the model coefficients. The problem with such constraints is that the results can differ substantially depending on the constraint chosen. Somewhat surprisingly, age-period-cohort models that specify one or more of ages and/or periods and/or cohorts as random effects are identified. This is the case without introducing an additional constraint. I label this identification as statistical model identification and show how statistical model identification comes about in mixed models and why which effects are treated as fixed and which are treated as random can substantially change the estimates of the age, period, and cohort effects. Copyright © 2017 John Wiley & Sons, Ltd.

Catalytic Z-selective olefin cross-metathesis for natural product synthesis.

Alkenes are found in many biologically active molecules, and there are a large number of chemical transformations in which alkenes act as the reactants or products (or both) of the reaction. Many alkenes exist as either the E or the higher-energy Z stereoisomer. Catalytic procedures for the stereoselective formation of alkenes are valuable, yet methods enabling the synthesis of 1,2-disubstituted Z alkenes are scarce. Here we report catalytic Z-selective cross-metathesis reactions of terminal enol ethers, which have not been reported previously, and of allylic amides, used until now only in E-selective processes. The corresponding disubstituted alkenes are formed in up to >98% Z selectivity and 97% yield. These transformations, promoted by catalysts that contain the highly abundant and inexpensive metal molybdenum, are amenable to gram-scale operations. Use of reduced pressure is introduced as a simple and effective strategy for achieving high stereoselectivity. The utility of this method is demonstrated by its use in syntheses of an anti-oxidant plasmalogen phospholipid, found in electrically active tissues and implicated in Alzheimer's disease, and the potent immunostimulant KRN7000.

Integration-independent Transgenic Huntington Disease Fragment Mouse Models Reveal Distinct Phenotypes and Life Span in Vivo.

The cascade of events that lead to cognitive decline, motor deficits, and psychiatric symptoms in patients with Huntington disease (HD) is triggered by a polyglutamine expansion in the N-terminal region of the huntingtin (HTT) protein. A significant mechanism in HD is the generation of mutant HTT fragments, which are generally more toxic than the full-length HTT. The protein fragments observed in human HD tissue and mouse models of HD are formed by proteolysis or aberrant splicing of HTT. To systematically investigate the relative contribution of the various HTT protein proteolysis events observed in vivo, we generated transgenic mouse models of HD representing five distinct proteolysis fragments ending at amino acids 171, 463, 536, 552, and 586 with a polyglutamine length of 148. All lines contain a single integration at the ROSA26 locus, with expression of the fragments driven by the chicken ß-actin promoter at nearly identical levels. The transgenic mice N171-Q148 and N552-Q148 display significantly accelerated phenotypes and a shortened life span when compared with N463-Q148, N536-Q148, and N586-Q148 transgenic mice. We hypothesized that the accelerated phenotype was due to altered HTT protein interactions/complexes that accumulate with age. We found evidence for altered HTT complexes in caspase-2 fragment transgenic mice (N552-Q148) and a stronger interaction with the endogenous HTT protein. These findings correlate with an altered HTT molecular complex and distinct proteins in the HTT interactome set identified by mass spectrometry. In particular, we identified HSP90AA1 (HSP86) as a potential modulator of the distinct neurotoxicity of the caspase-2 fragment mice (N552-Q148) when compared with the caspase-6 transgenic mice (N586-Q148).