High-affinity antibodies specific to the core region of the tau protein exhibit diagnostic and therapeutic potential for Alzheimer's disease.

Background: Recent advances in blood-based biomarker discovery are paving the way for simpler, more accessible diagnostic tools that can detect early signs of Alzheimer's disease (AD). Recent successes in the development of amyloid-targeting immunotherapy approaches mark an important advancement in providing new options for the treatment of AD. We have developed a set of high-affinity monoclonal antibodies (mAbs) to tau protein that have the potential as tools for diagnosis and treatment of AD.

Considerations for biomarker strategies in clinical trials investigating tau-targeting therapeutics for Alzheimer's disease.

The use of biomarker-led clinical trial designs has been transformative for investigating amyloid-targeting therapies for Alzheimer's disease (AD). The designs have ensured the correct selection of patients on these trials, supported target engagement and have been used to support claims of disease modification and clinical efficacy. Ultimately, this has recently led to approval of disease-modifying, amyloid-targeting therapies for AD; something that should be noted for clinical trials investigating tau-targeting therapies for AD.

Utility of Blood-Based Tau Biomarkers for Mild Cognitive Impairment and Alzheimer's Disease: Systematic Review and Meta-Analysis.

Objectives: With the development of new technologies capable of detecting low concentrations of Alzheimer's disease (AD) relevant biomarkers, the idea of a blood-based diagnosis of AD is nearing reality. This study aims to consider the evidence of total and phosphorylated tau as blood-based biomarkers for mild cognitive impairment (MCI) and AD when compared to healthy controls.

Methods: Studies published between 1 January 2012 and 1 May 2021 (Embase and MEDLINE databases) measuring plasma/serum levels of tau in AD, MCI, and control cohorts were screened for eligibility, including quality and bias assessment via a modified QUADAS.

Current Progress and Future Directions for Tau-Based Fluid Biomarker Diagnostics in Alzheimer's Disease.

Despite continued efforts, there remain no disease-modifying drugs approved by the United States Food and Drug Administration (FDA) or European Medicines Agency (EMA) to combat the global epidemic of Alzheimer's disease. Currently approved medicines are unable to delay disease progression and are limited to symptomatic treatment. It is well established that the pathophysiology of this disease remains clinically silent for decades prior to symptomatic clinical decline.

Predicting aggression in adults with intellectual disability: A pilot study of the predictive efficacy of the Current Risk of Violence and the Short Dynamic Risk Scale.

Background: Structured assessments have been shown to assist professionals to evaluate the risk of aggression in secure services for general offender populations and more recently among adults with intellectual disabilities. There is a need to develop intellectual disability sensitive measures for predicting risk of aggression in community samples, especially tools with a focus on dynamic variables.

Methods: The study prospectively followed 28 participants for up to 2 months to test whether the Current Risk of Violence (CuRV) and Short Dynamic Risk Scale (SDRS) were able to predict verbal and physical aggression in a community sample of adults with intellectual disability.

How effective are risk assessments/measures for predicting future aggressive behaviour in adults with intellectual disabilities (ID): A systematic review and meta-analysis.

Background: Risk assessments assist professionals in the identification and management of risk of aggression. The present study aimed to systematically review evidence on the efficacy of assessments for managing the risk of physical aggression in adults with intellectual disabilities (ID).

Methods: A literature search was conducted using the databases PsycINFO, EMBASE, MEDLINE, Web of Science, and Google Scholar.

Prospective dynamic assessment of risk of sexual reoffending in individuals with an intellectual disability and a history of sexual offending behaviour.

Background: The purpose of the present study was to add to the literature on the predictive accuracy of a dynamic intellectual disability specific risk assessment tool.

Method: A dynamic risk assessment for sexual reoffending (ARMIDILO-S), a static risk assessment for sexual offending (STATIC-99), and a static risk assessment for violence (Violence Risk Appraisal Guide [VRAG]) were completed for a sample of 64 adult males with an intellectual disability.

Results: The dynamic risk assessment for sexual offenders with an intellectual disability resulted in the best prediction of sexual reoffending (ARMIDILO-S area under the curve (AUC) = 0.

Distracted driving behaviors of adults while children are in the car.

Background: Cell phone use while driving is common and can result in driver distraction. However, data on the frequency of this behavior with other occupants in the vehicle are lacking. This study investigates whether adult drivers engage in cell phone use with passengers in the car and determines whether the frequency of these behaviors was modified if the passenger was a child.

Fractured neck of femur patient care improved by simulated fast-track system.

Background: Fractured neck of femur patients represent a large demand on trauma services, and timely management results in improvements in morbidity and mortality. NICE guidance, advocating surgery on the day of admission or the following day, emphasises this. We set out to investigate whether a simulated fast-track management system could improve neck of femur fracture patient care.

How do static and dynamic risk factors work together to predict violent behaviour among offenders with an intellectual disability?

Background: Research on risk assessment with offenders with an intellectual disability (ID) has largely focused on estimating the predictive accuracy of static or dynamic risk assessments, or a comparison of the two approaches. The aim of this study was to explore how static and dynamic risk variables may 'work together' to predict violent behaviour.

Methods: Data from 212 offenders with an ID were analysed.

Establishing an injury prevention program to address pediatric pedestrian collisions.

The implementation of a pedestrian safety education program in public schools can change the knowledge and beliefs about safe pedestrian behaviors among students and their parents or caregivers with the goal of reducing morbidity and mortality of children. WalkSafe is a well-established, multiphase pedestrian safety intervention program. This program has been shown to improve pedestrian safety knowledge of school-aged children in kindergarten through grade 5 after receiving a 3-day educational curriculum.

Pulseless electrical activity, focused abdominal sonography for trauma, and cardiac contractile activity as predictors of survival after trauma.

Background: Pulseless electrical activity (PEA) secondary to both blunt and penetrating trauma is associated with minimal survival. The pericardial view of the focused abdominal sonography for trauma (p-FAST) can differentiate between patients with and without organized cardiac activity and may assist in the decision to terminate ongoing resuscitation.

Methods: A retrospective review was performed for all patients presenting to a level I trauma center from January 2006 through January/2009 who had PEA on arrival or developed PEA in the emergency department.

Gluteal compartment syndrome following posterior cruciate ligament repair.

Compartment syndrome is a rare but important complication which may occur following injury or surgery to the lower limb. We present a case of contralateral gluteal compartment syndrome following arthroscopic posterior cruciate ligament repair. In order to gain a greater understanding of this complication, we undertook a limited study to investigate the effect of patient position on gluteal compartment pressures.

Preoperative administration of epoetin alfa to reduce transfusion requirements in elderly patients having primary total hip or knee reconstruction.

Avoidance of allogeneic blood transfusion is challenging in elderly patients with multiple comorbid conditions, who need major elective orthopaedic surgery. We conducted a study comparing the safety and efficacy of preoperative recombinant human erythropoietin (epoetin alfa) in patients having major elective orthopaedic surgery and in matched historical control patients. Patients aged 70 years or more undergoing primary total knee arthroplasty (TKA) or total hip arthroplasty (THA) were given two or three doses, respectively, of epoetin alfa (40,000 IU).

Identification of caveolae and detection of caveolin in normal human osteoblasts.

Caveolae, specialised regions of the cell membrane which have been detected in a wide range of mammalian cells, have not been described in bone cells. They are plasmalemmal invaginations, 50 to 100 nm in size, characterised by the presence of the structural protein, caveolin, which exists as three subtypes. Caveolin-1 and caveolin-2 are expressed in a wide range of cell types whereas caveolin-3 is thought to be a muscle-specific subtype.

beta(3)-adrenoceptor deficiency blocks nitric oxide-dependent inhibition of myocardial contractility.

The cardiac beta-adrenergic pathway potently stimulates myocardial performance, thereby providing a mechanism for myocardial contractile reserve. beta-Adrenergic activation also increases cardiac nitric oxide (NO) production, which attenuates positive inotropy, suggesting a possible negative feedback mechanism. Recently, in vitro studies suggest that stimulation of the beta(3)-adrenoceptor results in a negative inotropic effect through NO signaling.

Contribution of caveolin protein abundance to augmented nitric oxide signaling in conscious dogs with pacing-induced heart failure.

Myocardial NO signaling appears elevated in heart failure (HF). Whether this results from increased NO production, induction of the high-output NO synthase (NOS)2 isoform, or changes in NOS regulatory pathways (such as caveolae) remains controversial. We tested the hypothesis that increased abundance of caveolin-3 and/or sarcolemmal caveolae contribute to increased NO signaling in pacing-induced HF.

Effect of prosthetic titanium wear debris on mitogen-induced monocyte and lymphoid activation.

Wear debris generated by joint implant components has been reported to activate inflammatory and immune cells. Particulate debris derived from prosthetic material induces monocytes/macrophages, lymphocytes, synoviocytes, and fibroblasts to secrete cellular products, such as cytokines, which mediate inflammation. It has been speculated that degradation products impair the ability of inflammatory and immune cells to mount a protective response against noxious agents and infectious organisms by interfering with cell activation.

A combined analysis of D22S278 marker alleles in affected sib-pairs: support for a susceptibility locus for schizophrenia at chromosome 22q12. Schizophrenia Collaborative Linkage Group (Chromosome 22).

Several groups have reported weak evidence for linkage between schizophrenia and genetic markers located on chromosome 22q using the lod score method of analysis. However these findings involved different genetic markers and methods of analysis, and so were not directly comparable. To resolve this issue we have performed a combined analysis of genotypic data from the marker D22S278 in multiply affected schizophrenic families derived from 11 independent research groups worldwide.

Failure to find a chromosome 18 pericentric linkage in families with schizophrenia.

A recent report of a possible linkage of bipolar affective disorder to a pericentric region of chromosome 18 initiated the present investigation to search for a similar linkage in 32 families with schizophrenia. The results of a study using 5 markers mapped to this region show negative lod scores and only weak evidence for any linkage by nonparametric analyses. If the previously reported finding is a true positive linkage for bipolar disorder, then either it is unlikely to be related to the genetics of schizophrenia, or the proportion of families linked to this region is small.

Study of the Huntington's disease (HD) gene CAG repeats in schizophrenic patients shows overlap of the normal and HD affected ranges but absence of correlation with schizophrenia.

The CAG repeats in the Huntington's disease gene were investigated in chromosomes from 71 unrelated schizophrenic persons and 18 patients with schizoaffective disorder in order to determine if any of these patients had abnormal expansions. All of the probands had repeat sizes in the normal range (< 35 repeats) and there was no significant difference between the allele distributions of these patients and the normal controls. The families of two patients with 32 repeats and one patient with 34 repeats were investigated further and showed no uniform segregation of the disease with the large repeat alleles.

Search for linkage to schizophrenia on the X and Y chromosomes.

Markers for X chromosome loci were used in linkage studies of a large group of small families (n = 126) with at least two schizophrenic members in one sibship. Based on the hypothesis that a gene for schizophrenia could be X-Y linked, with homologous loci on both X and Y, our analyses included all families regardless of the pattern of familial inheritance. Lod scores were computed with both standard X-linked and a novel X-Y model, and sib-pair analyses were performed for all markers examining the sharing of maternal alleles.