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BACKGROUND: Trials of monoclonal antibodies that target various forms of amyloid at different stages of Alzheimer's disease have had mixed results. METHODS: We tested solanezumab, which targets monomeric amyloid, in a phase 3 trial involving persons with preclinical Alzheimer's disease. Persons 65 to 85 years of age with a global Clinical Dementia Rating score of 0 (range, 0 to 3, with 0 indicating no cognitive impairment and 3 severe dementia), a score on the Mini-Mental State Examination of 25 or more (range, 0 to 30, with lower scores indicating poorer cognition), and elevated brain amyloid levels on 18F-florbetapir positron-emission tomography (PET) were enrolled. Participants were randomly assigned in a 1:1 ratio to receive solanezumab at a dose of up to 1600 mg intravenously every 4 weeks or placebo. The primary end point was the change in the Preclinical Alzheimer Cognitive Composite (PACC) score (calculated as the sum of four z scores, with higher scores indicating better cognitive performance) over a period of 240 weeks. RESULTS: A total of 1169 persons underwent randomization: 578 were assigned to the solanezumab group and 591 to the placebo group. The mean age of the participants was 72 years, approximately 60% were women, and 75% had a family history of dementia. At 240 weeks, the mean change in PACC score was -1.43 in the solanezumab group and -1.13 in the placebo group (difference, -0.30; 95% confidence interval, -0.82 to 0.22; P=0.26). Amyloid levels on brain PET increased by a mean of 11.6 centiloids in the solanezumab group and 19.3 centiloids in the placebo group. Amyloid-related imaging abnormalities (ARIA) with edema occurred in less than 1% of the participants in each group. ARIA with microhemorrhage or hemosiderosis occurred in 29.2% of the participants in the solanezumab group and 32.8% of those in the placebo group. CONCLUSIONS: Solanezumab, which targets monomeric amyloid in persons with elevated brain amyloid levels, did not slow cognitive decline as compared with placebo over a period of 240 weeks in persons with preclinical Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Mixed model repeated measures (MMRM) is the most common analysis approach used in clinical trials for Alzheimer's disease and other progressive diseases measured with continuous outcomes over time. The model treats time as a categorical variable, which allows an unconstrained estimate of the mean for each study visit in each randomized group. Categorizing time in this way can be problematic when assessments occur off‐schedule, as including off‐schedule visits can induce bias, and excluding them ignores valuable information and violates the intention to treat principle. This problem has been exacerbated by clinical trial visits which have been delayed due to the COVID19 pandemic. As an alternative to MMRM, we propose a constrained longitudinal data analysis with natural cubic splines that treats time as continuous and uses test version effects to model the mean over time. Compared to categorical‐time models like MMRM and models that assume a proportional treatment effect, the spline model is shown to be more parsimonious and precise in real clinical trial datasets, and has better power and Type I error in a variety of simulation scenarios. [ABSTRACT FROM AUTHOR]

BioID is a proximity labeling strategy whose goal is to identify in vivo protein-protein interactions. The central components of this strategy are modified biotin ligase enzymes that promiscuously add biotin groups to proteins in close proximity. The transferred biotin group provides a powerful tag for purification and thus identification of interacting proteins. While a variety of modified biotin ligases were created for BioID, the original enzymes were inefficient, required long incubation times, and high intracellular biotin concentrations for protein labeling. These limitations hinder the application of BioID in contexts such as developing embryos where processes such as cell division and cell fate decisions occur rapidly. Recently, a new biotin ligase called TurboID was developed that addressed many of the deficiencies of previous enzymes. In this paper we compare TurboID to the BioID2 biotin ligase in developing Xenopus embryos. We find that the TurboID enzyme has several advantages over the BioID2 enzyme. TurboID labels proteins efficiently without the addition of additional biotin and occurs at a range of temperatures compatible with the culturing of Xenopus embryos. Biotinylation events occurred rapidly and were limited by TurboID expression and not its activity. Thus, TurboID is an efficient tool for BioID applications in Xenopus embryos and its use should facilitate the identification of interacting proteins in specific networks and complexes during Xenopus development. • Enzymes for proximity labeling applications were compared in Xenopus embryos. • TurboID was an efficient enzyme for proximity biotinylation. • Proteins were labeled rapidly and without the addition of biotin by TurboID. [ABSTRACT FROM AUTHOR]

Longitudinal studies are ubiquitous in medical and clinical research. Sample size computations are critical to ensure that these studies are sufficiently powered to provide reliable and valid inferences. There are several methodologies for calculating sample sizes for longitudinal studies that depend on many considerations including the study design features, outcome type and distribution, and proposed analytical methods. We briefly review the literature and describe sample size formulas for continuous longitudinal data. We then apply the methods using example studies comparing treatment versus control groups in randomized trials assessing treatment effect on clinical outcomes. We also introduce a Shiny app that we developed to assist researchers with obtaining required sample sizes for longitudinal studies by allowing users to enter required pilot estimates. For Alzheimer's studies, the app can estimate required pilot parameters using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Illustrative examples are used to demonstrate how the package and app can be used to generate sample size and power curves. The package and app are designed to help researchers easily assess the operating characteristics of study designs for Alzheimer's clinical trials and other research studies with longitudinal continuous outcomes. Data used in preparation of this article were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.edu). [ABSTRACT FROM AUTHOR]

Meniscal allograft transplantation provides treatment options for patients with a meniscus-deficient knee with lifestyle-limiting symptoms in the absence of advanced degenerative changes. Meniscal transplantation helps to restore the native biomechanics of the involved knee, which may provide chondroprotective effects and restoring additional knee stability. Improvements in pain, function, and activity level have been seen in appropriately selected patients undergoing transplantation. Although various surgical implantation options exist, the majority focus on reproducing native attachments of the meniscal roots to allow near normal mechanics. Although meniscal transplantation may serve as a salvage procedure for symptomatic patients with a meniscus-deficient knee, it may prevent or delay the necessity of a more invasive arthroplasty procedure. [ABSTRACT FROM AUTHOR]

The Rapid Risk of Violence Screen (RROVS) is a brief screening tool that is designed for use in community-based behavioral health service settings to identify people who may need comprehensive violence risk assessment. This study examined the association between the RROVS total score and future criminal justice involvement including violent offenses. Results from this study suggest that the RROVS screening tool has predictive validity as it is associated with later criminal justice involvement with a violent offense. The RROVS may be a helpful tool for community-based behavioral health providers to screen incoming clients for violence risk to inform whether additional assessment for violence potential is warranted. [ABSTRACT FROM AUTHOR]

Objective: To clarify the preclinical stage of Alzheimer's disease by estimating when β‐amyloid accumulation first becomes associated with changes in cognition. Methods: Here we studied a large group (N = 4432) of cognitively unimpaired individuals who were screened for inclusion in the A4 trial (age 65–85) to assess the effect of subthreshold levels of β‐amyloid on cognition and to identify which cognitive domains first become affected. Results: β‐amyloid accumulation was linked to significant cognitive dysfunction in cognitively unimpaired participants with subthreshold levels of β‐amyloid in multiple measures of memory (Logical Memory Delayed Recall, P = 0.03; Free and Cued Selective Reminding Test, P < 0.001), the Preclinical Alzheimer's Cognitive Composite (P = 0.01), and was marginally associated with decreased executive function (Digit Symbol Substitution, P = 0.07). Significantly, decreased cognitive scores were associated with suprathreshold levels of β‐amyloid, across all measures (P < 0.05). The Free and Cued Selective Reminding Test, a list recall memory test, appeared most sensitive to β‐amyloid ‐related decreases in average cognitive scores, outperforming all other cognitive domains, including the narrative recall memory test, Logical Memory. Interpretation: Clinical trials for cognitively unimpaired β‐amyloid‐positive individuals will include a large number of individuals where mechanisms downstream from β‐amyloid pathology are already activated. These findings have implications for primary and secondary prevention of Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Background: Adults with Down syndrome (DS) are at very high risk for Alzheimer's disease (AD). Neurofilament light (NF-L) has emerged as a potential blood-based biomarker of neurodegeneration due to AD.Objective: To understand the relationship between plasma NF-L with age, brain amyloid, and tau pathology, neurodegeneration as well as cognitive and functional performance.Methods: We analyzed imaging data as well as cognitive measures in relation to plasma NF-L in adults with DS, ages 30 to 60 who were enrolled in the Down Syndrome Biomarker Initiative.Results: We found significant correlations between NF-L plasma concentrations and amyloid pathology (r = 0.73, p = 0.007, pa = 0.041) and significant inverse correlations with regional glucose metabolism in 5 of 6 regions examined, which were Anterior cingulate (r = -0.55, p = 0.067, pa = 0.067), Posterior cingulate r = -0.90, p < 0.001, pa < 0.001), Lateral Temporal (r = -0.78, p = 0.004, pa = 0.012), Frontal cortex (r = -0.90, p < 0.001, p pa < 0.001), Parietal cortex (r = -0.82, p = 0.002, pa = 0.008), Precuneus (r = -0.73, pa = 0.010, pa = 0.020), and with hippocampal volume (r = -0.52, p = 0.084, pa = 0.084); and an inverse correlation with direct measures of cognition: CAMCOG (r = -0.66 p = 0.022, pa = 0.066) and positive correlation with CANTAB Paired Associates Learning (PAL) error rate (r = 0.68, p = 0.015, pa = 0.060). Finally, we found inverse relationships with informant-based functional measures (r = -0.57, p = 0.059, pa = 0.084) and OMQ-PF (r = -0.74, p = 0.008, pa = 0.041).Conclusion: Plasma NF-L is associated with progressive neurodegeneration as well as with declines in cognitive and functional measures in adults with DS. [ABSTRACT FROM AUTHOR]

The article discusses the use of machine learning in sentencing recidivists in the U.S. Topics mentioned include the risk of relying on a recidivism score to sentence a prisoner, the disapproval on a single philosophy of punishment, the sentencing guidelines in the country, and the problem associated with replacing discretion.

Introduction: Since the onset of the Global War on Terror close to 50,000 United States service members have been injured in combat, many of these injuries would have previously been fatal. Among these injuries, open acetabular fractures are at an increased number due to the high percentage of penetrating injuries such as high velocity gunshot wounds and blast injuries. These injuries lead to a greater degree of contamination, and more severe associated injuries. There is a significantly smaller proportion of the classic blunt trauma mechanism typically seen in civilian trauma.Methods: We performed a retrospective review of the Department of Defense Trauma Registry into which all US combat-injured patients are enrolled, as well as reviewed local patient medical records, and radiologic studies from March 2003 to April 2012. Eighty seven (87) acetabular fractures were identified with 32 classified as open fractures. Information regarding mechanism of injury, fracture pattern, transfusion requirements, Injury Severity Score (ISS), and presence of lower extremity amputations was analyzed.Results: The mechanism of injury was an explosive device in 59% (n=19) of patients with an open acetabular fracture; the remaining 40% (n=13) were secondary to ballistic injury. In contrast, in the closed acetabular fracture cohort 38% (21/55) of fractures were due to explosive devices, and all remaining (n=34) were secondary to blunt trauma such as falls, motor vehicle collisions, or aircraft crashes. Patients with open acetabular fractures required a median of 17units of PRBC within the first 24h after injury. The mean ISS was 32 in the open group compared with 22 in the closed group (p=0.003). In the open fracture group nine patients (28%) sustained bilateral lower extremity amputations, and 10 patients (31%) ultimately underwent a hip disarticulation or hemi-pelvectomy as their final amputation level.Discussion: Open acetabular fractures represent a significant challenge in the management of combat-related injuries. High ISS and massive transfusion requirements are common in these injuries. This is one of the largest series reported of open acetabular fractures. Open acetabular fractures require immediate damage control surgery and resuscitation as well as prolonged rehabilitation due to their severity. The dramatic number of open acetabular fractures (37%) in this review highlights the challenge in treatment of combat related acetabular fractures. [ABSTRACT FROM AUTHOR]

Glenohumeral instability secondary to glenohumeral bone loss presents a complex problem to the treating surgeon because of the complex biomechanics of the glenohumeral joint and its reliance on numerous dynamic and static stabilizers. The role of glenoid bone loss, specifically inferior-anterior glenoid bone loss, has been well characterized in the setting of recurrent unidirectional instability with greatly improved clinical results when following an algorithmic reconstructive approach to the location and percentage of overall bone loss. Furthermore, as the role of bipolar bone loss in the setting of glenohumeral engagement becomes more apparent, surgeons can more effectively address those lesions contributing to the recurrent instability. As such, surgeons should carefully and critically asses patients with recurrent anterior instability to optimize patient clinical outcomes. [ABSTRACT FROM AUTHOR]

The glenohumeral joint is one of the most frequently dislocated joints and occurs with increasing frequency in collision and contact athletes, especially those in sports that repeatedly place the glenohumeral joint in a position of vulnerability. Nonoperative management of shoulder instability especially in young contact athletes results in unacceptably high recurrence rates; thus, early surgical stabilization has become commonplace. Surgical stabilization typically yields acceptable outcomes. However, recurrent anterior instability may occur following a previous stabilization procedure at rates of 7% to 12%. Recurrent glenohumeral instability represents a treatment challenge for orthopedic surgeons as it not only has the potential to result in subsequent surgery, therapy, and missed activity time, but also has been associated with long-term degenerative joint changes. Thus, recurrent instability requires close examination to determine underlying pathology leading to failure. Evaluation of underlying pathology requires consideration of patient activity-related factors, hyperlaxity and multidirectional instability, glenoid bone loss, glenoid track lesions, and other pathologic lesions. Revision surgical stabilization approaches include arthroscopic and open stabilization, as well as glenoid osseous augmentation procedures. Postoperative rehabilitation and release to sports and activity must be tailored to protect the shoulder from continued instability. Understanding that risk of recurrent glenohumeral instability and the risk factors associated with it are essential so that these factors may be mitigated and recurrent instability prevented. [ABSTRACT FROM AUTHOR]

Importance: Among cognitively normal individuals, elevated brain amyloid (defined by cerebrospinal fluid assays or positron emission tomography regional summaries) can be related to risk for later Alzheimer-related cognitive decline.Objective: To characterize and quantify the risk for Alzheimer-related cognitive decline among cognitively normal individuals with elevated brain amyloid.Design, Setting, and Participants: Exploratory analyses were conducted with longitudinal cognitive and biomarker data from 445 cognitively normal individuals in the United States and Canada. Participants were observed from August 23, 2005, to June 7, 2016, for a median of 3.1 years (interquartile range, 2.0-4.2 years; maximum follow-up, 10.3 years) as part of the Alzheimer's Disease Neuroimaging Initiative (ADNI).Exposures: Individuals were classified at baseline as having normal (n = 243) or elevated (n = 202) brain amyloid using positron emission tomography amyloid imaging or a cerebrospinal fluid assay of amyloid β.Main Outcomes and Measures: Outcomes included scores on the Preclinical Alzheimer Cognitive Composite (PACC; a sum of 4 baseline standardized z scores, which decreases with worse performance), Mini-Mental State Examination (MMSE; 0 [worst] to 30 [best] points), Clinical Dementia Rating Sum of Boxes (CDR-Sum of Boxes; 0 [best] to 18 [worst] points), and Logical Memory Delayed Recall (0 [worst] to 25 [best] story units).Results: Among the 445 participants (243 with normal amyloid, 202 with elevated amyloid), mean (SD) age was 74.0 (5.9) years, mean education was 16.4 (2.7) years, and 52% were women. The mean score for PACC at baseline was 0.00 (2.60); for MMSE, 29.0 (1.2); for CDR-Sum of Boxes, 0.04 (0.14); and for Logical Memory Delayed Recall, 13.1 (3.3). Compared with the group with normal amyloid, those with elevated amyloid had worse mean scores at 4 years on the PACC (mean difference, 1.51 points [95% CI, 0.94-2.10]; P < .001), MMSE (mean difference, 0.56 points [95% CI, 0.32-0.80]; P < .001), and CDR-Sum of Boxes (mean difference, 0.23 points [95% CI, 0.08-0.38]; P = .002). For Logical Memory Delayed Recall, between-group score was not statistically significant at 4 years (mean difference, 0.73 story units [95% CI, -0.02 to 1.48]; P = .056).Conclusions and Relevance: Exploratory analyses of a cognitively normal cohort followed up for a median of 3.1 years suggest that elevation in baseline brain amyloid level, compared with normal brain amyloid level, was associated with higher likelihood of cognitive decline, although the findings are of uncertain clinical significance. Further research is needed to assess the clinical importance of these differences and measure longer-term associations. [ABSTRACT FROM AUTHOR]

Cognitively-normal people with evidence of β-amyloid (Aβ) pathology and subtle cognitive dysfunction are believed to be at high risk for progression to mild cognitive impairment due to Alzheimer's disease (AD). Clinical trials in later stages of AD typically include a coprimary endpoint to demonstrate efficacy on both cognitive and functional assessments. Recent trials focus on cognitively-normal people, but functional decline has not been explored for trial designs in this group. The goal of this study was therefore to characterize cognitive and functional decline in (1) cognitively-normal people converting to mild cognitive impairment (MCI) and (2) cognitively-normal β-amyloid-positive (Aβ+) people. Specifically, we sought to identify and compare the cognitive and functional assessments and their weighted combinations that maximize the longitudinal decline specific to these 2 groups. We studied 68 people who converted from normal cognition to MCI and 70 nonconverters, as well as 137 Aβ+ and 210 β-amyloid-negative cognitively-normal people. We used bootstrap aggregation and cross-validated mixed-models to estimate the distribution of weights applied to cognitive and functional outcomes to form composites. We also evaluated best subset optimization. Using optimized composites, we estimated statistical power for a variety of clinical trial scenarios. Overall, 55.4% of cognitively-normal to MCI converters were Aβ+. Large gains in power estimates were obtained when requiring participants to have both subtle cognitive dysfunction and Aβ pathology compared with requiring Aβ pathology alone. Additional power resulted when including functional as well as cognitive outcomes as part of the composite. Composites formed by applying equal weights to all measures provided the highest estimates of cross-validated power, although similar to both continuous weight optimization and best subset optimization. Using a composite to detect a 30% slowing of decline, 80% power was obtained for predicted Aβ+ converters with 375 completers/arm for a 30-month trial using a combination of cognitive/ functional measures. In the Aβ+ group, power to approach levels suitable for a phase III clinical trial would require considerably larger sample sizes. Composites incorporating both cognitive and functional measures may substantially increase the power of a trial in a preclinical (Aβ+) AD population with subtle evidence of cognitive dysfunction. [ABSTRACT FROM AUTHOR]

Landing and squat tasks have been utilized to assess lower extremity biomechanics associated with anterior cruciate ligament loading and injury risks. The purpose of this study was to identify the differences and correlations in knee and hip mechanics during a single-leg landing, a single-leg squat, a double-leg landing, and a double-leg squat. Seventeen male and 17 female recreational athletes performed landings and squats when kinematic and kinetic data were collected. ANOVAs showed significant differences (p < 0.00001) for maximum knee flexion angles, maximum hip flexion angles, maximum knee abduction angles, maximum hip adduction angles, and maximum external knee abduction moments among squats and landings. For maximum knee and hip flexion angles, significant correlations (r ≥ 0.5, p ≤ 0.003) were observed between the two landings and between the two squats. For maximum knee abduction and hip adduction angles and maximum external knee abduction moments, significant correlations were mostly found between the two landings, and between the single-leg squat and landings (r ≥ 0.54, p ≤ 0.001). Individuals are likely to demonstrate different profiles of injury risks when screened using different tasks. While a double-leg landing should be considered as a priority in screening, a single-leg squat may be used as a surrogate to assess frontal plane motion and loading. [ABSTRACT FROM AUTHOR]

Oregon's Public Mental Health System employs a large number of unlicensed personnel with limited formal mental health training, both in state hospitals and in residential treatment programs. These mental health paraprofessionals often have the most frequent and direct contact with seriously mentally ill individuals, and therefore have significant impact on their lives. The authors describe organization as well as clinical and administrative supervision of a mostly paraprofessional team working with severely and persistently mentally ill (SPMI) criminal offenders. The purpose of this article is to delineate the most important factors allowing for effective and safe utilization of the fairy unsophisticated personnel in the community based-secure treatment facility for individuals under criminal commitment, conditionally released from Oregon State Hospital. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The primary aim of this study was to assess the relationship between adenovirus 38 (AD36)-specific antibodies and obesity in children. METHODS: A cross-sectional study of children 8 to 18 years of age was performed. Children were classified according to BMI percentile as nonobese (<95th percentile) or obese (⩾95th percentile). The presence of AD36-specific neutralizing antibodies was assessed by using the serum neutralization assay. RESULTS: A total of 124 children (median age: 13.6 years) were studied. Of those children, 46% were nonobese and 54% were obese. AD36 positivity was present in 19 children (15%). The majority of children found to be AD36-positive were obese (15 [78%] of 19 children). AD36 positivity was significantly (P < .05) more frequent in obese children (15 [22%] of 67 children) than nonobese children (4 [7%] of 57 children). Among the subset of children who were obese, those who were AD36-positive had significantly larger anthropometric measures, including weight, BMI, waist circumference, and waist/height ratio. CONCLUSION: These data support an association of obesity and higher body weight with the presence of neutralizing antibodies to AD36 in children. If a cause-and-effect relationship is established, it would have considerable implications for the prevention and treatment of childhood pbesity. [ABSTRACT FROM AUTHOR]

Background Arthrofibrosis following total knee arthroplasty ( TKA) is a common problem, which can be frustrating to both the patient and treating physician and can dramatically compromise post-operative function. Current treatment options for TKA arthrofibrosis include watchful waiting, injections, physical therapy, manipulation under anaesthesia, arthroscopic/open lysis of adhesions and revision surgery. We present a novel technique to treat acute and chronic stiffness following TKA, which we call hydraulic distension. Methods A retrospective pre- and post-operative inpatient and outpatient record review of three patients treated with hydraulic distension for arthrofibrosis following TKA at a single institution. Results Three patients with a mean age of 74 years (68-78) underwent hydraulic distension of the knee at a mean of 23.4 ± 18.4 months (9 weeks to 36 months) following primary TKA. The mean pre-distension maximum flexion was 86.7 ± 10.4°, and the mean post-distension flexion was 110 ± 13.2° (23.3° increase). The patients maintained a mean 110 ± 20° flexion (23.3° increase) at a mean follow-up of 11.7 months (1 week to 29 months). There were no complications. Conclusion We present a novel technique for managing arthrofibrosis following TKA that has not been previously reported. This is an effective, safe procedure, with our patients experiencing a mean 23° increased knee flexion at the most recent follow-up. [ABSTRACT FROM AUTHOR]

Critical to development of new therapies for Alzheimer's disease (AD) is the ability to detect clinical or pathological change over time. Clinical outcome measures typically used in therapeutic trials have unfortunately proven to be relatively variable and somewhat insensitive to change in this slowly progressive disease. For this reason, development of surrogate biomarkers that identify significant disease-associated brain changes are necessary to expedite treatment development in AD. Since AD pathology is present in the brain many years prior to clinical manifestation, ideally we want to develop biomarkers of disease that identify abnormal brain structure or function even prior to cognitive decline. Magnetic resonance imaging, fluorodeoxyglucose positron emission tomography, new amyloid imaging techniques, and spinal fluid markers of AD all have great potential to provide surrogate endpoint measures for AD pathology. The Alzheimer's disease neuroimaging initiative (ADNI) was developed for the distinct purpose of evaluating surrogate biomarkers for drug development in AD. Recent evidence from ADNI demonstrates that imaging may provide more sensitive, and earlier, measures of disease progression than traditional clinical measures for powering clinical drug trials in Alzheimer's disease. This review discusses recently presented data from the ADNI dataset, and the importance of imaging in the future of drug development in AD. [ABSTRACT FROM AUTHOR]

Muscle wasting is a critical feature of patients afflicted by acquired immune deficiency syndrome (AIDS), cancer, or chronic inflammatory diseases. In a mouse model of muscle wasting, TNF-α induces oxidative stress and nitric oxide synthase-2 (NOS2) and decreases myogenin, Jun-D, and creatinine kinase muscle isoform (CKM) expression. Here, we studied 12 patients with muscle wasting due to cancer (N = 10) or AIDS (N = 2) and 4 control subjects. We show that in skeletal muscle of cachectic patients there is 1) increased expression and activity of the TNF-α signaling, including TNF-α mRNA, activation of TNFR1, and TNF-α-associated to TNFR1; 2) increased oxidative stress, as determined by the presence of malondialdehyde-lysine adducts; 3) increased NOS2 mRNA and protein; 4) decreased expression of Jun-D, myogenin, myosin, and CKM mRNA and protein; 5) impaired CKM-E box binding activities, associated with decreased Jun-D/myogenin activities; and 6) oxidative modification and ubiquitination of Jun-D. These studies show that these molecular pathways are modulated in association with muscle wasting in patients with cancer or AIDS, and whether or not they cause muscle wasting remains to be determined. [ABSTRACT FROM AUTHOR]

The property of synergy and its detection are discussed. A response surface is said to possess synergy if it is monotone in each argument and its level curves are convex. Detecting this is useful in the study of combination drug therapies, where the goal is enhanced response with diminished side effect. One way to detect synergy is to fit a surface with linear level curves under the assumption of asynergy and observe the residuals. We explore an algorithm to accomplish this asynergistic regression via a reduction in dimensionality and connections to semiparametric monotonic linear index models (Cavanagh and Sherman, 1998). We see that the asynergistic model is a generalized version of the monotonic linear index model where the linear level curves are not restricted to be parallel. [ABSTRACT FROM AUTHOR]

BACKGROUND: Interpatient variability in the kinetics of peripheral blood progenitor cell (PBPC) mobilization is commonly seen with conventional chemotherapy-based mobilization regimens. This necessitates the availability of leukapheresis (LP) facilities 7 days a week. STUDY DESIGN AND METHODS: The efficacy of an approach where LP was invariably commenced on Day 11 after intermediate-dose cyclophosphamide followed by sequential administration of granulocyte-macrophage–colony-stimulating factor (CSF) and granulocyte–CSF (Cy/GM/G) was retrospectively analyzed in 225 consecutive, unselected patients undergoing autologous hematopoietic stem cell transplantation for all diagnoses other than acute leukemia at our center. Cy/GM/G was scheduled to avoid weekend LP. RESULTS: After Cy/GM/G, a CD34+ cell yield of at least 2.0 × 106 per kg was achieved in 90.7 percent of patients. Optimal yield (OY; ≥5 × 106 or 10 × 106 CD34+ cells/kg depending on diagnosis) was achieved in 67.6 percent of patients. Only three patients (1.3%) required LP on Saturday or Sunday. Febrile neutropenia (FN) was encountered in 5.3 percent. PBPC yield was highest on Day 1 of LP (p < 0.001). In multivariate analyses, platelet (PLT) count on Day 1 of LP (PLT-D1LP) was positively associated with achievement of OY (p < 0.001). PLT-D1LP and diagnosis of myeloma were associated with a shorter time to achieve a CD34+ cell yield of at least 5 × 106 per kg (p < 0.001 and p = 0.002, respectively). CONCLUSION: Cy/GM/G with scheduled LP commencement on Day 11 enables optimal CD34+ cell yields in most patients undergoing autologous transplantation, despite a low risk of FN and avoidance of weekend LP. [ABSTRACT FROM AUTHOR]

The author reflects on his experience renting an apartment in Brooklyn in February 2000. He comments on the death of his landlady and the day on which movers brought her possessions to a warehouse. He describes how he discovered a box of letters addressed to and from a man named Russell, which also contained pornography, newspaper headings, suicide notes, and journal entries.

Background: Plasma neurofilament light chain (NfL) is a blood biomarker of neurodegeneration, including Alzheimer's disease. However, its usefulness may be influenced by common conditions in older adults, including amyloid-β (Aβ) deposition and cardiometabolic risk factors like hypertension, diabetes mellitus (DM), impaired kidney function, and obesity. This longitudinal observational study using the Alzheimer's Disease Neuroimaging Initiative cohort investigated how these conditions influence the prognostic capacity of plasma NfL. Methods: Non-demented participants (cognitively unimpaired or mild cognitive impairment) underwent repeated assessments including the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) scores, hippocampal volumes, and white matter hyperintensity (WMH) volumes at 6- or 12-month intervals. Linear mixed-effect models were employed to examine the interaction between plasma NfL and various variables of interest, such as Aβ (evaluated using Florbetapir positron emission tomography), hypertension, DM, impaired kidney function, or obesity. Results: Over a mean follow-up period of 62.5 months, participants with a mean age of 72.1 years (n = 720, 48.8% female) at baseline were observed. Higher plasma NfL levels at baseline were associated with steeper increases in ADAS-Cog scores and WMH volumes, and steeper decreases in hippocampal volumes over time (all p-values < 0.001). Notably, Aβ at baseline significantly enhanced the association between plasma NfL and longitudinal changes in ADAS-Cog scores (p-value 0.005) and hippocampal volumes (p-value 0.004). Regarding ADAS-Cog score and WMH volume, the impact of Aβ was more prominent in cognitively unimpaired than in mild cognitive impairment. Hypertension significantly heightened the association between plasma NfL and longitudinal changes in ADAS-Cog scores, hippocampal volumes, and WMH volumes (all p-values < 0.001). DM influenced the association between plasma NfL and changes in ADAS-Cog scores (p-value < 0.001) without affecting hippocampal and WMH volumes. Impaired kidney function did not significantly alter the association between plasma NfL and longitudinal changes in any outcome variables. Obesity heightened the association between plasma NfL and changes in hippocampal volumes only (p-value 0.026). Conclusion: This study suggests that the prognostic capacity of plasma NfL may be amplified in individuals with Aβ or hypertension. This finding emphasizes the importance of considering these factors in the NfL-based prognostic model for neurodegeneration in non-demented older adults. [ABSTRACT FROM AUTHOR]

Reports that the synthesis of phylogenetic and ecological approaches is surely a positive development in evolutionary ecology. Phylogeny considered not a correction and a constraint; Challenges ahead.

• The time-from-Aβ pathology measure identifies early signs of disease progression. • Increases in tau pathology and cognitive dysfunction occur 4–8 years prior to Aβ-positivity. • Slowing the spread of tau pathology and cognitive decline may require treatment prior to significant Aβ pathology. Estimate the time-course of the spread of key pathological markers and the onset of cognitive dysfunction in Alzheimer's disease. In a cohort of 335 older adults, ranging in cognitive functioning, we estimated the time of initial changes of Aβ, tau, and decreases in cognition with respect to the time of Aβ-positivity. Small effect sizes of change in CSF Aβ42 and regional Aβ PET were estimated to occur several decades before Aβ-positivity. Increases in CSF tau occurred 7–8 years before Aβ-positivity. Temporoparietal tau PET showed increases 4–5 years before Aβ-positivity. Subtle cognitive dysfunction was observed 4–6 years before Aβ-positivity. Increases in tau and cognitive dysfunction occur years before commonly used thresholds for Aβ-positivity. Explicit estimates of the time for these events provide a clearer picture of the time-course of the amyloid cascade and identify potential windows for specific treatments. [ABSTRACT FROM AUTHOR]

Despite the substantial impact of depression on individuals and healthcare utilization, little is known about the specific relationship between depression severity and total cost of care (TCC). This study evaluates the association between depression symptom severity and TCC and how changes in severity affect TCC. The analysis was conducted using insurance claims data and data from electronic health records between January 1, 2019 and December 31, 2020. Inclusion criteria comprised insured individuals with coverage during 2019 or 2020, aged one year or older, and identified as having depression in at least one year of the study. Depression symptom severity was assessed using the screening Identification and Stratification (IDS) framework and data available to the research team. The main outcome was TCC per member per month (PMPM) evaluated across the two-year period. Across 2019 and 2020, 744,854 members met inclusion criteria. A total of 369,460 members were studied across both years. Greater depression symptom severity was associated with higher TCC across both years. Unchanged severity was associated with limited change in TCC from 2019 to 2020. Decrease in depression symptoms was associated with an average $41 reduction in PMPM spend, whereas increase in depression symptom severity was associated with an average $608 increase. Limitations include fragmented data, retrospective design that limits causality, and the IDS framework design. Changes in depression symptom severity were significantly associated with changes in TCC. Findings reveal financial and clinical opportunities associated with early identification and targeted management of depression. • 13.6 % of members were identified as having depression in 2019 and 15.8 % in 2020. • Expenses for severe depression were 117 % higher than for minimal severity in 2020. • Decrease in depression severity was associated with an average $41 reduction in cost. • Members who had an increase in severity had 25 % to 48 % higher costs. [ABSTRACT FROM AUTHOR]

Case: We present a 26-year-old active duty man who sustained a coccygeal fracture and gluteus maximus hematoma after a fall from height during training. The patient returned 3 weeks postinjury with symptoms and physical examination findings concerning for gluteal compartment syndrome. An expanding gluteal hematoma was confirmed on imaging and the patient was taken to the operating room for emergent evacuation and endovascular hemostasis. Conclusions: This case of gluteal compartment syndrome is a unique contribution to the literature with respect to the specific vascular injury observed and the delayed presentation of gluteal compartment syndrome. [ABSTRACT FROM AUTHOR]

Background: There are limited data comparing the beach-chair (BC) versus lateral decubitus (LD) position for arthroscopic anterior shoulder stabilization. Purpose: To identify predictors of instability recurrence and revision after anterior shoulder stabilization and evaluate surgical position and glenoid bone loss as independent predictors of recurrence and revision at short- and midterm follow-ups. Study Design: Cohort study; Level of evidence, 3. Methods: A consecutive series of 641 arthroscopic anterior stabilization procedures were performed from 2005 to 2019. All shoulders were evaluated for glenohumeral bone loss on magnetic resonance imaging. The primary outcomes of interest were recurrence and revision. Multivariable logistic regression models were used to assess the relationships of outcomes with age, position, glenoid bone loss group, and track. Results: A total of 641 shoulders with a mean age of 22.3 years (SD, 4.45 years) underwent stabilization and were followed for a mean of 6 years. The overall 1-year recurrent instability rate was 3.3% (21/641) and the revision rate was 2.8% (18/641). At 1 year, recurrence was observed in 2.3% (11/487) and 6.5% (10/154) of BC and LD shoulders, respectively. The 5-year recurrence and revision rates were 15.7% (60/383) and 12.8% (49/383), respectively. At 5 years, recurrence was observed in 16.4% (48/293) and 13.3% (12/90) of BC and LD shoulders, respectively. Multivariable modeling demonstrated that surgical position was not associated with a risk of recurrence after 1 year (odds ratio [OR] for LD vs BC, 1.39; P =.56) and 5 years (OR for LD vs BC, 1.32; P =.43), although younger age at index surgery was associated with a higher risk of instability recurrence (OR, 1.73 per SD [4.1 years] decrease in age; P <.03). After 1 and 5 years, surgical position results were similar in a separate multivariable logistic regression model of revision surgery as the dependent variable, when adjusted for age, surgical position, bone loss group, and track. At 5 years, younger age was an independent risk factor for revision: OR 1.68 per SD (4.1 years) decrease in age (P <.05). Conclusion: Among fellowship-trained orthopaedic surgeons, there was no difference in rates of recurrence and revision surgery after performing arthroscopic anterior stabilization in either the BC or the LD position at 1- and 5-year follow-ups. In multivariable analysis, younger age, but not surgical position, was an independent risk factor for recurrence. [ABSTRACT FROM AUTHOR]

Objective: Neuropsychiatric symptoms (NPS) are common in mild cognitive impairment (MCI) and even more in Alzheimer's disease (AD). The symptom‐based cluster including nighttime disturbances, depression, appetite changes, anxiety, and apathy (affective and vegetative symptoms) was associated with an increased risk of dementia in MCI and has common neuroanatomical associations. Our objective was to investigate the differences in brain morphology associations with affective and vegetative symptoms between three groups: cognitively normal older adults (CN), MCI and AD. Material and Methods: Alzheimer's Disease Neuroimaging Initiative data of 223 CN, 367 MCI and 175 AD, including cortical volumes, surface areas and thicknesses and severity scores of the five NPS were analyzed. A whole‐brain vertex‐wise general linear model was performed to test for intergroup differences (CN‐MCI, CN‐AD, AD‐MCI) in brain morphology associations with five NPS. Multiple regressions were conducted to investigate cortical change as a function of NPS severity in the AD‐MCI contrast. Results: We found (1) signature differences in nighttime disturbances associations with prefrontal regions in AD‐MCI, (2) signature differences in NPS associations with temporal regions in AD‐MCI for depression and in CN‐AD for anxiety, (3) decreased temporal metrics in MCI as nighttime disturbances and depression severity increased, (4) decreased pars triangularis metrics in AD as nighttime disturbances and apathy severity increased. Conclusion: Each NPS seems to have a signature on brain morphology. Affective and vegetative NPS were primarily associated with prefrontal and temporal regions. These signatures open the possibility of potential future assessments of links between brain morphology and NPS on an individual level. Key points: Signature differences in nighttime disturbances associations with prefrontal regions in Alzheimer's disease mild cognitive impairment (AD‐MCI).Signature differences in Neuropsychiatric symptoms associations with temporal regions in AD‐MCI for de‐pression and in cognitively normal‐AD for anxiety.Dreased temporal metrics in MCI as nighttime dis‐turbances and depression severity increased.Decreased pars triangularis metrics in AD as nighttime disturbances and apathy severity increased. [ABSTRACT FROM AUTHOR]

Background: Participant eligibility for the A4 Study was determined by amyloid PET imaging. Given the disadvantages of amyloid PET imaging in accessibility and cost, blood-based biomarkers may serve as a sufficient biomarker and more cost-effective screening tool for patient enrollment into preclinical AD trials. Objective: To determine if a blood-based screening test can adequately identify amyloid burden in participants screened into a preclinical AD trial. Methods: In this cross-sectional study, 224 participants from the A4 Study received an amyloid PET scan (18Florbetapir) within 90 days of blood sample collection. Blood samples from all study participants were processed within 2 h after phlebotomy. Plasma amyloid measures were quantified by Shimazdu and C2 N Diagnostics using mass spectrometry-based platforms. A corresponding subset of blood samples (n = 100) was processed within 24 h after phlebotomy and analyzed by C2 N. Results: Plasma Aβ42/Aβ40 demonstrated the highest association for Aβ accumulation in the brain with an AUC 0.76 (95%CI = 0.69, 0.82) at C2 N and 0.80 (95%CI = 0.75, 0.86) at Shimadzu. Blood samples processed to plasma within 2 h after phlebotomy provided a better prediction of amyloid PET status than blood samples processed within 24 h (AUC 0.80 versus 0.64; p < 0.001). Age, sex, and APOE ɛ4 carrier status did not the diagnostic performance of plasma Aβ42/Aβ40 to predict amyloid PET positivity in A4 Study participants. Conclusion: Plasma Aβ42/Aβ40 may serve as a potential biomarker for predicting elevated amyloid in the brain. Utilizing blood testing over PET imaging may improve screening efficiency into clinical trials. [ABSTRACT FROM AUTHOR]

Rates of tau accumulation in cognitively unimpaired older adults are subtle, with magnitude and spatial patterns varying in recent reports. Regional accumulation also likely varies in the degree to which accumulation is amyloid-β-dependent. Thus, there is a need to evaluate the pattern and consistency of tau accumulation across multiple cognitively unimpaired cohorts and how these patterns relate to amyloid burden, in order to design optimal tau end points for clinical trials. Using three large cohorts of cognitively unimpaired older adults, the Anti-Amyloid Treatment in Asymptomatic Alzheimer's and companion study, Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (n = 447), the Alzheimer's Disease Neuroimaging Initiative (n = 420) and the Harvard Aging Brain Study (n = 190), we attempted to identify regions with high rates of tau accumulation and estimate how these rates evolve over a continuous spectrum of baseline amyloid deposition. Optimal combinations of regions, tailored to multiple ranges of baseline amyloid burden as hypothetical clinical trial inclusion criteria, were tested and validated. The inferior temporal cortex, fusiform gyrus and middle temporal cortex had the largest effect sizes of accumulation in both longitudinal cohorts when considered individually. When tau regions of interest were combined to find composite weights to maximize the effect size of tau change over time, both longitudinal studies exhibited a similar pattern—inferior temporal cortex, almost exclusively, was optimal for participants with mildly elevated amyloid β levels. For participants with highly elevated baseline amyloid β levels, combined optimal composite weights were 53% inferior temporal cortex, 31% amygdala and 16% fusiform. At mildly elevated levels of baseline amyloid β, a sample size of 200/group required a treatment effect of 0.40–0.45 (40–45% slowing of tau accumulation) to power an 18-month trial using the optimized composite. Neither a temporal lobe composite nor a global composite reached 80% power with 200/group with an effect size under 0.5. The focus of early tau accumulation on the medial temporal lobe has resulted from the observation that the entorhinal cortex is the initial site to show abnormal levels of tau with age. However, these abnormal levels do not appear to be the result of a high rate of accumulation in the short term, but possibly a more moderate rate occurring early with respect to age. While the entorhinal cortex plays a central role in the early appearance of tau, it may be the inferior temporal cortex that is the critical region for rapid tau accumulation in preclinical Alzheimer's disease. [ABSTRACT FROM AUTHOR]

More than 50 million older people worldwide are suffering from dementia, and this number is estimated to increase to 150 million by 2050. Greater caregiver burdens and financial impacts on the healthcare system are expected as we wait for an effective treatment for dementia. Researchers are constantly exploring new therapies and screening approaches for the early detection of dementia. Artificial intelligence (AI) is widely applied in dementia research, including machine learning and deep learning methods for dementia diagnosis and progression detection. Computerized apps are also convenient tools for patients and caregivers to monitor cognitive function changes. Furthermore, social robots can potentially provide daily life support or guidance for the elderly who live alone. This review aims to provide an overview of AI applications in dementia research. We divided the applications into three categories according to different stages of cognitive impairment: (1) cognitive screening and training, (2) diagnosis and prognosis for dementia, and (3) dementia care and interventions. There are numerous studies on AI applications for dementia research. However, one challenge that remains is comparing the effectiveness of different AI methods in real clinical settings. [ABSTRACT FROM AUTHOR]

Background: Pectoralis major tendon ruptures are commonly described as rare injuries affecting men between 20 and 40 years of age, with generally excellent results after surgical repair. However, this perception is based on a relatively small number of case series and prospective studies in the orthopaedic literature. Purpose: To determine the incidence of pectoralis major tendon ruptures in the active-duty military population and the demographic risk factors for a rupture and to describe the outcomes of surgical treatment. Study Design: Case control study; Level of evidence, 3. Methods: We utilized the Military Health System Data Repository (MDR) to identify all active-duty military personnel surgically treated for a pectoralis major tendon rupture between January 2012 and December 2014. Electronic medical records were searched for patients’ demographic information, injury characteristics, and postoperative complications and outcomes. Risk factors for a rupture were calculated using Poisson regression, based on population counts obtained from the MDR. Risk factors for a postoperative complication, the need for revision surgery, and the inability to continue with active duty were determined using univariate analysis and multivariate logistic regression. Results: A total of 291 patients met inclusion criteria. The mean patient age was 30.5 years, all patients were male, and the median follow-up period was 18 months. The incidence of injuries was 60 per 100,000 person-years over the study period. Risk factors for a rupture included service in the Army, junior officer or junior enlisted rank, and age between 25 and 34 years. White race and surgery occurring >6 weeks after injury were significant risk factors for a postoperative complication. Among the 214 patients with a minimum of 12 months’ clinical follow-up, 95.3% were able to return to military duty. Junior officer/enlisted status was a significant risk factor for failure to return to military duty. Conclusion: Among military personnel, Army soldiers and junior officer/enlisted rank were at highest risk of pectoralis major tendon ruptures, and junior personnel were at highest risk of being unable to return to duty after surgical treatment. Although increasing time from injury to surgery was not a risk factor for treatment failure or inability to return to duty, it did significantly increase the risk of a postoperative complication. [ABSTRACT FROM AUTHOR]

Background: Ultrasound-guided percutaneous cryoneurolysis is an analgesic technique in which a percutaneous probe is used to reversibly ablate a peripheral nerve(s) using exceptionally low temperature, and has yet to be evaluated with randomized, controlled trials. Pain after mastectomy can be difficult to treat, and the authors hypothesized that the severity of surgically related pain would be lower on postoperative day 2 with the addition of cryoanalgesia compared with patients receiving solely standard-of-care treatment.Methods: Preoperatively, participants at one enrolling center received a single injection of ropivacaine, 0.5%, paravertebral nerve block at T3 or T4, and perineural catheter. Participants subsequently underwent an active or sham ultrasound-guided percutaneous cryoneurolysis procedure of the ipsilateral T2 to T5 intercostal nerves in a randomized, patient- and observer-masked fashion. Participants all received a continuous paravertebral block with ropivacaine, 0.2%, until the early morning of discharge (usually postoperative day 2). The primary endpoint was the average pain level measured using a 0 to 10 numeric rating scale the afternoon of postoperative day 2. Participants were followed for 1 yr.Results: On postoperative day 2, participants who had received active cryoneurolysis (n = 31) had a median [interquartile range] pain score of 0 [0 to 1.4] versus 3.0 [2.0 to 5.0] in patients given sham (n = 29): difference -2.5 (97.5% CI, -3.5 to -1.5), P < 0.001. There was evidence of superior analgesia through month 12. During the first 3 weeks, cryoneurolysis lowered cumulative opioid use by 98%, with the active group using 1.5 [0 to 14] mg of oxycodone compared with 72 [20 to 120] mg in the sham group (P < 0.001). No oral analgesics were required by any patient between months 1 and 12. After 1 yr chronic pain had developed in 1 (3%) active compared with 5 (17%) sham participants (P < 0.001).Conclusions: Percutaneous cryoneurolysis markedly improved analgesia without systemic side effects or complications after mastectomy.Editor’s Perspective: [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a progressive disorder associated with cognitive dysfunction that alters the brain's functional connectivity. Assessing these alterations has become a topic of increasing interest. However, a few studies have examined different stages of AD from a complex network perspective that cover different topological scales. This study used resting state fMRI data to analyze the trend of functional connectivity alterations from a cognitively normal (CN) state through early and late mild cognitive impairment (EMCI and LMCI) and to Alzheimer's disease. The analyses had been done at the local (hubs and activated links and areas), meso (clustering, assortativity, and rich-club), and global (small-world, small-worldness, and efficiency) topological scales. The results showed that the trends of changes in the topological architecture of the functional brain network were not entirely proportional to the AD progression. There were network characteristics that have changed non-linearly regarding the disease progression, especially at the earliest stage of the disease, i.e., EMCI. Further, it has been indicated that the diseased groups engaged somatomotor, frontoparietal, and default mode modules compared to the CN group. The diseased groups also shifted the functional network towards more random architecture. In the end, the methods introduced in this paper enable us to gain an extensive understanding of the pathological changes of the AD process. [ABSTRACT FROM AUTHOR]

Background: Although posterior glenohumeral instability is becoming an increasingly recognized cause of shoulder pain, the role of posterior glenoid bone loss on outcomes remains incompletely understood. Purposes: To prospectively determine the amount of bone loss associated with posterior instability events and to determine predisposing factors based on preinstability imaging. Study Design: Cross-sectional study; Level of evidence, 3. Methods: A total of 1428 shoulders were evaluated prospectively for ≥4 years. At baseline, a subjective history of shoulder instability was ascertained for each patient, and bilateral noncontrast magnetic resonance imaging (MRI) scans of the shoulders were obtained regardless of any reported history of shoulder instability. The cohort was prospectively followed during the study period, and those who were diagnosed with posterior glenohumeral instability were identified. Postinjury MRI scans were obtained and compared with the screening MRI scans. Glenoid version, perfect-circle-based bone loss was measured for each patient's pre- and postinjury MRI scans using previously described methods. Results: Of the 1428 shoulders that were prospectively followed, 10 shoulders sustained a first-time posterior instability event and 3 shoulders sustained a recurrent posterior instability event. At baseline, 11 of 13 shoulders had some amount of glenoid dysplasia and/or bone loss. The change in glenoid bone loss was 5.4% along the axis of greatest loss (95% CI, 3.8%-7.0%; P =.009), 4.4% at the glenoid equator (95% CI, 2.7%-6.2%; P =.016), and 4.2% of total glenoid area (95% CI, 2.9%-5.3%; P =.002). Recurrent glenoid instability was associated with a greater amount of absolute bone loss along the axis of greatest loss compared with first-time instability (recurrent: 16.8% ± 1.1%; 95% CI, 14.6%-18.9%; first-time: 10.0% ± 1.5%; 95% CI, 7.0%-13.0%; P =.005). Baseline glenoid retroversion ≥10° was associated with a significantly greater percentage of bone loss along the axis of greatest loss (≥10° of retroversion: 13.5% ± 2.0%; 95% CI, 9.6%-17.4%; <10° of retroversion: 8.5% ± 0.8%; 95% CI, 7.0%-10.0%; P =.045). Conclusions: Posterior glenohumeral instability events were associated with glenoid bone loss of 5%. The amount of glenoid bone loss after a recurrent posterior glenohumeral instability event was greater than that after first-time instability. Glenoid retroversion ≥10° was associated with a greater amount of posterior glenoid bone loss after a posterior instability event. [ABSTRACT FROM AUTHOR]

Reduced cerebrospinal fluid amyloid-β42 and increased retention of florbetapir positron emission tomography are biomarkers reflecting cortical amyloid load in Alzheimer's disease. However, these measurements do not always agree and may represent partly different aspects of the underlying Alzheimer's disease pathology. The goal of this study was therefore to test if cerebrospinal fluid and positron emission tomography amyloid-β biomarkers are independently related to other Alzheimer's disease markers, and to examine individuals who are discordantly classified by these two biomarker modalities. Cerebrospinal fluid and positron emission tomography amyloid-β were measured at baseline in 769 persons [161 healthy controls, 68 subjective memory complaints, 419 mild cognitive impairment and 121 Alzheimer's disease dementia, mean age 72 years (standard deviation 7 years), 47% females] and used to predict diagnosis, APOE ε4 carriage status, cerebral blood flow, cerebrospinal fluid total-tau and phosphorylated-tau levels (cross-sectionally); and hippocampal volume, fluorodeoxyglucose positron emission tomography results and Alzheimer's Disease Assessment Scale-cognitive subscale scores (longitudinally). Cerebrospinal fluid and positron emission tomography amyloid-β were highly correlated, but adjusting one of these predictors for the other revealed that they both provided partially independent information when predicting diagnosis, APOE ε4, hippocampal volume, metabolism, cognition, total-tau and phosphorylated-tau (the 95% confidence intervals of the adjusted effects did not include zero). Cerebrospinal fluid amyloid-β was more strongly related to APOE ε4 whereas positron emission tomography amyloid-β was more strongly related to tau levels (P < 0.05). Discordance (mainly isolated cerebrospinal fluid amyloid-β positivity) differed by diagnostic group (P < 0.001) and was seen in 21% of cognitively healthy people but only 6% in dementia patients. The finding that cerebrospinal fluid and positron emission tomography amyloid-β provide partially independent information about a wide range of Alzheimer's measures supports the theory that these modalities represent partly different aspects of Alzheimer's pathology. The fact that mismatch, with positive cerebrospinal fluid amyloid-β but normal positron emission tomography amyloid-β, is relatively common in cognitively healthy people may be considered when using these biomarkers to identify early stage Alzheimer's disease. Reduced cerebrospinal fluid amyloid-β may be more strongly related to early stage Alzheimer's disease, whereas increased positron emission tomography amyloid-β may be more strongly related to disease progression. [ABSTRACT FROM AUTHOR]

Background: The common technique using a basal infusion for an ambulatory continuous peripheral nerve blocks frequently results in exhaustion of the local anesthetic reservoir before resolution of surgical pain. This study was designed to improve and prolong analgesia by delaying initiation using an integrated timer and delivering a lower hourly volume of local anesthetic as automated boluses. The hypothesis was that compared with a traditional continuous infusion, ropivacaine administered with automated boluses at a lower dose and 5-h delay would (1) provide at least noninferior analgesia (difference in average pain no greater than 1.7 points) while both techniques were functioning (average pain score day after surgery) and (2) result in a longer duration (dual primary outcomes).Methods: Participants (n = 70) undergoing foot or ankle surgery with a popliteal-sciatic catheter received an injection of ropivacaine 0.5% with epinephrine (20 ml) and then were randomized to receive ropivacaine (0.2%) either as continuous infusion (6 ml/h) initiated before discharge or as automated boluses (8 ml every 2 h) initiated 5 h after discharge using a timer. Both groups could self-deliver supplemental boluses (4 ml, lockout 30 min); participants and outcome assessors were blinded to randomization. All randomized participants were included in the data analysis.Results: The day after surgery, participants with automated boluses had a median [interquartile range] pain score of 0.0 [0.0 to 3.0] versus 3.0 [1.8 to 4.8] for the continuous infusion group, with an odds ratio of 3.1 (95% CI, 1.23 to 7.84; P = 0.033) adjusting for body mass index. Reservoir exhaustion in the automated boluses group occurred after a median [interquartile range] of 119 h [109 to 125] versus 74 h [57 to 80] for the continuous infusion group (difference of 47 h; 95% CI, 38 to 55; P < 0.001 adjusting for body mass index).Conclusions: For popliteal-sciatic catheters, replacing a continuous infusion initiated before discharge with automated boluses and a start-delay timer resulted in better analgesia and longer infusion duration.Editor’s Perspective: [ABSTRACT FROM AUTHOR]

Background Celiac disease is present in ~1% of the general population in the United States and Europe. Despite the availability of inexpensive serologic screening tests, ~85% of individuals with celiac disease remain undiagnosed and there is an average delay in diagnosis of symptomatic individuals with celiac disease that ranges from ~5.8-11 years. This delay is often attributed to the use of a case-based approach for detection rather than general population screening for celiac disease, and deficiencies at the level of health care professionals. This study aimed to assess if patient-centered barriers have a role in impeding serologic screening for celiac disease in individuals from populations that are clinically at an increased risk for celiac disease. Methods 119 adults meeting study inclusion criteria for being at a higher risk for celiac disease were recruited from the general population. Participants completed a survey/questionnaire at the William K. Warren Medical Research Center for Celiac Disease that addressed demographic information, celiac disease related symptoms (gastrointestinal and extraintestinal), family history, co-morbid diseases and conditions associated with celiac disease, and patient-centered barriers to screening for celiac disease. All participants underwent serologic screening for celiac disease using the IgA tissue transglutaminase antibody (IgA tTG) and, if positive, testing for IgA anti-endomysial antibody (IgA EMA) as a confirmatory test. Results Two barriers to serologic testing were significant across the participant pool. These were participants not knowing they were at risk for celiac disease before learning of the study, and participants not knowing where to get tested for celiac disease. Among participants with incomes less than $25,000/ year and those less than the median age, not having a doctor to order the test was a significant barrier, and this strongly correlated with not having health insurance. Symptoms and co-morbid conditions were similar among those whose IgA tTG were negative and those who tested positive. Conclusion There are significant patient-centered barriers that impede serologic screening and contribute to the delayed detection and diagnosis of celiac disease. These barriers may be lessened by greater education of the public and health care professionals about celiac disease symptoms, risk factors, and serologic testing. [ABSTRACT FROM AUTHOR]

Abstract: Supervised classification of land cover across space and time is a long-standing goal of the Earth Science community. Although most past and current analyses focus on detecting changes between two or more times, the opening of the USGS Landsat archive in 2009 has enabled exploration of methods for higher-frequency, time-serial monitoring of land cover dynamics. Modifying the protocols used to develop the 2001 National Land Cover Database (NLCD 2001), we fit a single classifier to a spatio-temporally distributed reference sample and applied the model to 55 Landsat-5 images covering a section of the North Carolina Piedmont Plateau from 1984 to 2007. A generalized classification scheme, multi-temporal sampling design, supervised classification based on intra-annual spectral indices, and design-based accuracy assessment yielded a time-series of 16 land cover maps from 1985 to 2006 with a spatial extent of 1.7×106 ha, minimum mapping unit of 1ha, and mean temporal interval of <2years. Comparable to accuracy of the NLCD 2001 Land Cover Layer for the region, overall accuracy for a spatio-temporally independent test sample was 75%, with κ=0.7. When weighted by class proportions, percent correctly classified and kappa rose to 88% and 0.84, respectively. The resulting map series shows spatially and temporally complex changes in water, urban, forest, and herbaceous cover resulting from natural and anthropogenic processes that would not be observable in either uni- or bi-temporal maps. Agricultural crop area dropped from ~45% in the 1980s to ~36% in the 1990s and then rose slightly to ~38% at the end of the period. Forest area increased to a maximum of ~55% in the 1990s and then dropped to ~53% in 2005. Urban growth appeared to be most rapid in the 1980s and 1990s and slowed thereafter. With continued focus on the semantics, causation, sampling, and uncertainty underlying spectral land cover classification, long-term series of Landsat images will provide increasingly robust, reliable records for a growing scientific user community. These multi-temporal datasets will be indispensable for understanding past land cover dynamics and predicting the implications of future change on the provision and management of ecosystem services. [Copyright &y& Elsevier]

Introduction and hypothesis: Given the increased prevalence of obesity and pelvic floor disorders (PFDs), we estimated changes in prevalence, bother, and quality of life (QOL) for PFDs in obese women undergoing bariatric surgery. We hypothesized PFDs would improve after surgical weight loss. Methods: The prevalence, bother, and QOL impact of PFDs were estimated using validated measures. McNemar's and paired t tests were used to compare pre- and postprocedural outcomes. Power calculations deemed that 90 individuals would achieve at least 80 % power to detect a decrease in prevalence of 12 %. Results: The baseline mean (± standard deviation) age and body mass index (BMI) of the 98 women were 43.3 ± 11.8 years and 39.7 ± 6.2 kg/m. BMI decreased to 34.4 ± 5.8 at 6 months and 34.0 ± 5.6 at 12 months. Whereas the overall prevalence of stress urinary incontinence (SUI) decreased from 22/69 (32 %) at baseline to 10/69 (15 %) at 6 months ( p = 0.006) and 14/69 (20 %) at 12 months ( p = 0.027), there were no significant decreases in overall prevalence of other PFDs. However, for women with SUI, overactive bladder (OAB), and anal incontinence at baseline, 11/23 (48 %), 8/11 (73 %) and 4/20 (20 %) resolved at 12 months, respectively. Pelvic Floor Impact Questionnaire scores decreased from baseline to 12 months ( p < 0.001). Mean visual analog scores for women with SUI, OAB, and anal incontinence decreased at 12 months. Conclusions: Surgical weight loss resulted in resolution of symptoms in nearly half of women with SUI and three quarters of women with OAB and was associated with significant improvement in QOL. [ABSTRACT FROM AUTHOR]

Objective: To investigate the association between suicide-related outcomes (SROs: wish to die, suicidal thoughts, and attempted suicide) and duration of smoking abstinence. Methods: The National Epidemiologic Survey on Alcohol and Related Conditions Wave 1 is a face-to-face survey of a representative sample of the U.S. adult population (N = 43,093). Analyses were done for a subsample of individuals (N = 13,691) who reported ever smoking, at least 2 weeks of lifetime depressed mood and SROs. Duration of abstinence was categorized as 1–24 hr (reference), 1 day to 12 months, and longer than 12 months. Results: Univariate analyses showed significant demographic associations (positive: female gender and being widowed/divorced/separated; negative: age and household income) with SROs. SROs were positively associated with major psychiatric disorders (dysthymia, major depression, generalized anxiety disorders, antisocial personality disorder, nicotine dependence, and alcohol abuse/dependence). Logistic regression showed that nonsmoking for more than a year compared with less than 24 hr (nonabstinence) was significantly associated with reduced risk for wish to die (odds ratio [OR]: 0.56, 95% CI: 0.49–0.65), suicidal thoughts (OR: 0.54, 95% CI: 0.48–0.62), and attempted suicide (OR: 0.32, 95 % CI: 0.26–0.41). With adjustments for lifetime psychiatric disorders, duration of abstinence was no longer significantly associated with the SROs. Conclusions: In the sample of ever-smokers with lifetime depressed mood, an apparent protective effect of increased duration of smoking abstinence on susceptibility to suicidal behavior was neutralized by the presence of psychiatric disorders. The causal direction of these relationships is unclear, and these cross-sectional findings need confirmation in future prospective studies. [ABSTRACT FROM AUTHOR]

Objective: At least 3 randomized, placebo-controlled, double-blind studies have supported the efficacy of computerized attention modification programs (AMPs) in reducing symptoms of anxiety in patients diagnosed with an anxiety disorder. In this study we examined patient characteristics that predicted response to AMP in a large sample of individuals diagnosed with generalized social phobia. Method: The sample comprised 112 individuals seeking treatment for generalized social phobia who completed a randomized clinical trial comparing AMP (n = 55) with a placebo condition (i.e., attention control condition; n = 57). We examined the following domains of baseline predictors of treatment response: (a) demographic characteristics (gender, age, ethnicity, years of education); (b) clinical characteristics (Axis I comorbidity, trait anxiety, depression); and (c) cognitive disturbance factors (attentional bias for social threat, social interpretation bias). Results: Results revealed that ethnicity predicted treatment response across both conditions: Participants who self-identified as non-Caucasian displayed better overall response than did Caucasians. The only prescriptive variable to emerge was attentional bias for social threat at preassessment. Participants in the AMP group who exhibited larger attentional bias scores displayed significantly greater reductions in clinician-rated social anxiety symptoms than did their counterparts in the attention control condition. Conclusions: These results suggest that AMP may be targeted to individuals most likely to benefit from these programs. [ABSTRACT FROM AUTHOR]