The critical role of primary care clinicians (PCCs) in Alzheimer’s disease (AD) prevention, diagnosis and management must evolve as new treatment paradigms and disease‐modifying therapies (DMTs) ...emerge. Our understanding of AD has grown substantially: no longer conceptualized as a late‐in‐life syndrome of cognitive and functional impairments, we now recognize that AD pathology builds silently for decades before cognitive impairment is detectable. Clinically, AD first manifests subtly as mild cognitive impairment (MCI) due to AD before progressing to dementia. Emerging optimism for improved outcomes in AD stems from a focus on preventive interventions in midlife and timely, biomarker‐confirmed diagnosis at early signs of cognitive deficits (i.e. MCI due to AD and mild AD dementia). A timely AD diagnosis is particularly important for optimizing patient care and enabling the appropriate use of anticipated DMTs. An accelerating challenge for PCCs and AD specialists will be to respond to innovations in diagnostics and therapy for AD in a system that is not currently well positioned to do so. To overcome these challenges, PCCs and AD specialists must collaborate closely to navigate and optimize dynamically evolving AD care in the face of new opportunities. In the spirit of this collaboration, we summarize here some prominent and influential models that inform our current understanding of AD. We also advocate for timely and accurate (i.e. biomarker‐defined) diagnosis of early AD. In doing so, we consider evolving issues related to prevention, detecting emerging cognitive impairment and the role of biomarkers in the clinic.
Although the early antidepressant trials which included severely ill and hospitalized patients showed substantial drug‐placebo differences, these robust differences have not held up in the trials of ...the past couple of decades, whether sponsored by pharmaceutical companies or non‐profit agencies. This narrowing of the drug‐placebo difference has been attributed to a number of changes in the conduct of clinical trials. First, the advent of DSM‐III and the broadening of the definition of major depression have led to the inclusion of mildly to moderately ill patients into antidepressant trials. These patients may experience a smaller magnitude of antidepressant‐placebo differences. Second, drug development regulators, such as the U.S. Food and Drug Administration and the European Medicines Agency, have had a significant, albeit underappreciated, role in determining how modern antidepressant clinical trials are designed and conducted. Their concerns about possible false positive results have led to trial designs that are poor, difficult to conduct, and complicated to analyze. Attempts at better design and patient selection for antidepressant trials have not yielded the expected results. As of now, antidepressant clinical trials have an effect size of 0.30, which, although similar to the effects of treatments for many other chronic illnesses, such as hypertension, asthma and diabetes, is less than impressive.
Despite heightened awareness of the clinical significance of social phobia, information is still lacking about putative subtypes, functional impairment, and treatment-seeking. New epidemiologic data ...on these topics are presented from the National Comorbidity Survey Replication (NCS-R).
The NCS-R is a nationally representative household survey fielded in 2001-2003. The World Health Organization (WHO) Composite International Diagnostic Interview Version 3.0 (CIDI 3.0) was used to assess 14 performance and interactional fears and DSM-IV social phobia.
The estimated lifetime and 12-month prevalence of social phobia are 12.1% and 7.1% respectively. Performance and interactional fears load onto a single latent factor, and there is little evidence for distinct subtypes based either on the content or the number of fears. Social phobia is associated with significant psychiatric co-morbidity, role impairment, and treatment-seeking, all of which have a dose-response relationship with number of social fears. However, social phobia is the focus of clinical attention in only about half of cases where treatment is obtained. Among non-co-morbid cases, those with the most fears were least likely to receive social phobia treatment.
Social phobia is a common, under-treated disorder that leads to significant functional impairment. Increasing numbers of social fears are associated with increasingly severe manifestations of the disorder.
Neuronal hyperexcitability is a feature of epilepsy and both inflammatory and neuropathic pain. M currents IK(M) play a key role in regulating neuronal excitability, and mutations in neuronal KCNQ2/3 ...subunits, the molecular correlates of IK(M), have previously been linked to benign familial neonatal epilepsy. Here, we demonstrate that KCNQ/M channels are also present in nociceptive sensory systems. IK(M) was identified, on the basis of biophysical and pharmacological properties, in cultured neurons isolated from dorsal root ganglia (DRGs) from 17-d-old rats. Currents were inhibited by the M-channel blockers linopirdine (IC50, 2.1 microm) and XE991 (IC50, 0.26 microm) and enhanced by retigabine (10 microm). The expression of neuronal KCNQ subunits in DRG neurons was confirmed using reverse transcription-PCR and single-cell PCR analysis and by immunofluorescence. Retigabine, applied to the dorsal spinal cord, inhibited C and Adelta fiber-mediated responses of dorsal horn neurons evoked by natural or electrical afferent stimulation and the progressive "windup" discharge with repetitive stimulation in normal rats and in rats subjected to spinal nerve ligation. Retigabine also inhibited responses to intrapaw application of carrageenan in a rat model of chronic pain; this was reversed by XE991. It is suggested that IK(M) plays a key role in controlling the excitability of nociceptors and may represent a novel analgesic target.
Accumulating evidence suggests that prenatal exposure to infection contributes to the etiology of schizophrenia. This line of investigation has been advanced by birth cohort studies that utilize ...prospectively acquired data from serologic assays for infectious and immune biomarkers. These investigations have provided further support for this hypothesis and permitted the investigation of new infectious pathogens in relation to schizophrenia risk. Prenatal infections that have been associated with schizophrenia include rubella, influenza, and toxoplasmosis. Maternal cytokines, including interleukin-8, are also significantly increased in pregnancies giving rise to schizophrenia cases. Although replication of these findings is required, this body of work may ultimately have important implications for the prevention of schizophrenia, the elaboration of pathogenic mechanisms in this disorder, and investigations of gene-environment interactions.
We introduce new modules in the open-source PyCBC gravitational-wave astronomy toolkit that implement Bayesian inference for compact-object binary mergers. We review the Bayesian inference methods ...implemented and describe the structure of the modules. We demonstrate that the PyCBC Inference modules produce unbiased estimates of the parameters of a simulated population of binary black hole mergers. We show that the parameters' posterior distributions obtained using our new code agree well with the published estimates for binary black holes in the first Advanced LIGO-Virgo observing run.
Most facets of mammalian physiology and behavior vary according to time of day, thanks to endogenous circadian clocks. Therefore, it is not surprising that many aspects of pharmacology and toxicology ...also oscillate according to the same 24-h clocks. Daily oscillations in abundance of proteins necessary for either drug absorption or metabolism result in circadian pharmacokinetics, and oscillations in the physiological systems targeted by these drugs result in circadian pharmacodynamics. These clocks are present in most cells of the body, organized in a hierarchical fashion. Interestingly, some aspects of physiology and behavior are controlled directly via a "master clock" in the suprachiasmatic nuclei of the hypothalamus, whereas others are controlled by "slave" oscillators in separate brain regions or body tissues. Recent research shows that these clocks can respond to different cues and thereby show different phase relationships. Therefore, full prediction of chronopharmacology in pathological contexts will likely require a systems biology approach that considers chronointeractions among different clock-regulated systems.
Aim
To evaluate and synthesize research that has investigated nurse resilience, to develop an understanding of what nurses' feel affects their resilience, their experiences and how resilience can ...impact individual nurses, patients and employers.
Design
Integrative review.
Data Sources
CINAHL, MEDLINE and PsycINFO, searched from the date each database was available to July 2019.
Review Methods
Primary research studies explicitly investigating resilience in any type of licensed nurse were eligible for inclusion. Studies were critically appraised for methodological quality using the Joanna Briggs Institute Quality Appraisal Framework. Data from each study were ed, coded and themes were identified according to the review aims and key findings of each study.
Results
Twenty‐seven studies met the inclusion criteria. Eight sub‐themes and three main themes were identified: The Resilient Nurse, Nurses' Experiences of Resilience and Employment Conditions and Nurse Resilience.
Conclusion
Nurse resilience is a complex and dynamic process, and high levels of resilience are associated with reduced psychological harm and increased well‐being. Attempts to determine the characteristics of the resilient nurse have been inconclusive and research has predominately focussed on individual factors which could affect resilience, with minimal research exploring external factors which affect nurse resilience including work environment and conditions. Nursing work was characterized by adversity and nurses described the development and use of strategies to maintain their resilience.
Impact
This review found that individual factors have received most attention in research investigating nurse resilience. Findings suggest that nurse resilience protects against negative psychological outcomes and nurses independently develop and use strategies to manage adversity. Factors in the workplace which affect resilience are under‐researched, and addressing this gap could assist with the development of comprehensive interventions and policies to build and maintain nurse resilience.
Population scale studies combining genetic information with molecular phenotypes (for example, gene expression) have become a standard to dissect the effects of genetic variants onto organismal ...phenotypes. These kinds of data sets require powerful, fast and versatile methods able to discover molecular Quantitative Trait Loci (molQTL). Here we propose such a solution, QTLtools, a modular framework that contains multiple new and well-established methods to prepare the data, to discover proximal and distal molQTLs and, finally, to integrate them with GWAS variants and functional annotations of the genome. We demonstrate its utility by performing a complete expression QTL study in a few easy-to-perform steps. QTLtools is open source and available at https://qtltools.github.io/qtltools/.
The development and practice of good leadership skills (distinct from management skills) enhances both an individual's career development, and their organization. However, universities are known to ...present unique issues around the development, and practice, of good leadership. Good leadership skills should be considered essential for university staff who train (and mentor) staff or students. Currently, there is no clear evidence that staff in the biological (life) sciences undergo formal (routine) leadership skills training (or appraisal). Furthermore, what leadership training this group needs, or wants, is unknown. A questionnaire was designed to explore leadership dimensions (roles, training, perceptions, and attitudes), and incorporated the Leadership Attitudes and Belief scale (LABS) instrument. Including LABS allows evaluation of leadership attitudes as either Systemic (individual responsibility) or Hierarchical (chain-of-command). Self-selecting biological science academics and staff were recruited using an online survey. Analysis focused on academic staff (lecturer/Assistant professor, and above), and explored the relationship of leadership dimensions with key categories (career stage, gender, age, role, and professional experience). Staff were found to be knowledgeable about what leadership is, but strongly desire formal training in leadership skills and practice. Importantly, staff did not have access to specific leadership training (but did have access to management training), but felt strongly that gaining leadership skills would improve their professional skill set. Analysis found that academics in the biological sciences were oriented towards Systemic leadership, a more collective and supportive approach. It was clear that while good leadership skills are highly valued by academic staff, in practice these skills are underprovided in the biological sciences workplace. This work provides a profile, and benchmark, of leadership (current skills, and desired needs) in the biological sciences. These results provide evidence for the need to embed specific leadership skills training into professional development (and teaching) programmes in the biological sciences.
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