Exon-focused targeted oligonucleotide microarray design increases detection of clinically relevant variants across multiple NHS genomic centres.

In recent years, chromosomal microarrays have been widely adopted by clinical diagnostic laboratories for postnatal constitutional genome analysis and have been recommended as the first-line test for patients with intellectual disability, developmental delay, autism and/or congenital abnormalities. Traditionally, array platforms have been designed with probes evenly spaced throughout the genome and increased probe density in regions associated with specific disorders with a resolution at the level of whole genes or multiple exons. However, this level of resolution often cannot detect pathogenic intragenic deletions or duplications, which represent a significant disease-causing mechanism.

Long-term evaluation of open-label pimavanserin safety and tolerability in Parkinson's disease psychosis.

Introduction: Pimavanserin is a selective 5-HT inverse agonist/antagonist approved for treating hallucinations and delusions associated with Parkinson's disease psychosis (PDP). Results from short-term, placebo-controlled studies demonstrated a positive benefit/risk profile. This multi-year, open-label study assessed long-term safety and tolerability of pimavanserin.

Catalytic Cycloisomerization onto a Carbonyl Oxygen.

We have found that terminal -vinylindoles bearing cycloalkanone substituents are excellent hydrogen atom acceptors, generating α-aminyl radicals with a variety of catalysts (Co(II)/H or Co(III)Cl precatalysts with silane reductants). These radicals can be converted to internal vinylindoles but eventually add to the oxygen of the cycloalkanone substituents. These cyclizations eventually furnish a densely functionalized dihydrofuran (a net cycloisomerization).

Sound and Vibration as Research Variables in Terrestrial Vertebrate Models.

Sound and vibration have been shown to alter animal behavior and induce physiological changes as well as to cause effects at the cellular and molecular level. For these reasons, both environmental factors have a considerable potential to alter research outcomes when the outcome of the study is dependent on the animal existing in a normal or predictable biological state. Determining the specific levels of sound or vibration that will alter research is complex, as species will respond to different frequencies and have varying frequencies where they are most sensitive.

The OPTIMIZE patient- and family-centered, primary care-based deprescribing intervention for older adults with dementia or mild cognitive impairment and multiple chronic conditions: study protocol for a pragmatic cluster randomized controlled trial.

Background: Most individuals with dementia or mild cognitive impairment (MCI) have multiple chronic conditions (MCC). The combination leads to multiple medications and complex medication regimens and is associated with increased risk for significant treatment burden, adverse drug events, cognitive changes, hospitalization, and mortality. Optimizing medications through deprescribing (the process of reducing or stopping the use of inappropriate medications or medications unlikely to be beneficial) may improve outcomes for MCC patients with dementia or MCI.

Utilization of an ICU Severity of Illness Scoring System to Triage Patients With ST-Elevation Myocardial Infarction.

Objective: To subjectively identify low-risk ST-elevation myocardial infarction (STEMI) patients and triage this low-risk population to an intermediate level of care.

Background: Many patients with STEMI are admitted to the intensive care unit (ICU), however, a large portion do not merit ICU admission. We sought to examine whether, among post-STEMI patients admitted to the ICU, if an easily obtainable subjective scoring system could predict low-risk patients and safely triage them to an intermediate level of care.

Using a citizens' jury approach to determine a good nutrition resource for pregnant women.

Objective: The development of user-friendly nutrition resources for pregnant women seldom involves end-users. This qualitative study used a citizens' jury approach to determine if our modification of a longstanding, frequently used dietitian-informed diet and diabetes booklet was deemed to be a good healthy eating resource for pregnant women.

Design: Midwives recruited thirteen first-time pregnant women not requiring specialist obstetric care or specialist dietetic advice for any reason.

Pancreatic Cancer Associated Fibroblasts (CAF): Under-Explored Target for Pancreatic Cancer Treatment.

Pancreatic cancer is the 4th leading cause of cancer deaths in the United States. The pancreatic cancer phenotype is primarily a consequence of oncogenes disturbing the resident pancreas parenchymal cell repair program. Many solid tumor types including pancreatic cancer have severe tumor fibrosis called desmoplasia.

Activation of the 15-lipoxygenase pathway in aspirin-exacerbated respiratory disease.

Background: Aspirin-exacerbated respiratory disease (AERD) is characterized by asthma, chronic rhinosinusitis with nasal polyps (CRSwNP), and an intolerance of medications that inhibit cyclooxygenase-1. Patients with AERD have more severe upper and lower respiratory tract disease than do aspirin-tolerant patients with CRSwNP. A dysregulation in arachidonic acid metabolism is thought to contribute to the enhanced sinonasal inflammation in AERD.

Macro-Scale Tread Patterns for Traction in the Intestine.

Goal: Tread patterns are widely used to increase traction on different substrates, with the tread scale, geometry and material being tailored to the application. This work explores the efficacy of using macro-scale tread patterns for a medical application involving a colon substrate - renowned for its low friction characteristics.

Methods: Current literature was first summarized before an experimental approach was used, based on a custom test rig with ex vivo porcine colon, to assess different macro-scale tread patterns.

H· Transfer-Initiated Synthesis of -Lactams: Interpretation of Cycloisomerization and Hydrogenation Ratios.

A cobaloxime/H system used to synthesize valuable -lactams from acrylamide molecules is described. In addition to cycloisomerized lactams, linear hydrogenated products were also observed. The amounts of the hydrogenation product were observed to correlate with the bulk of the substituent on the acrylamide nitrogen.

Neoadjuvant Capecitabine/Temozolomide for Locally Advanced or Metastatic Pancreatic Neuroendocrine Tumors.

Objectives: The combination chemotherapy regimen capecitabine/temozolomide (CAPTEM) is efficacious for metastatic well-differentiated pancreatic neuroendocrine tumors (PNETs), but its role in the neoadjuvant setting has not been established.

Methods: The outcomes of all patients with locally advanced or resectable metastatic PNETs who were treated with neoadjuvant CAPTEM between 2009 and 2017 at 2 high-volume institutions were retrospectively reviewed.

Results: Thirty patients with locally advanced PNET (n = 10) or pancreatic neuroendocrine hepatic metastases (n = 20) received neoadjuvant CAPTEM.

Racial/Ethnic Disparities in Atrial Fibrillation Treatment and Outcomes among Dialysis Patients in the United States.

Background: Because stroke prevention is a major goal in the management of ESKD hemodialysis patients with atrial fibrillation, investigating racial/ethnic disparities in stroke among such patients is important to those who could benefit from strategies to maximize preventive measures.

Methods: We used the United States Renal Data System to identify ESKD patients who initiated hemodialysis from 2006 to 2013 and then identified those with a subsequent atrial fibrillation diagnosis and Medicare Part A/B/D. Patients were followed for 1 year for all-cause stroke, mortality, prescription medications, and cardiovascular disease procedures.

Intratumoral Immunotherapy for Early-stage Solid Tumors.

The unprecedented benefits of immunotherapy in advanced malignancies have resulted in increased interests in exploiting immune stimulatory agents in earlier-stage solid tumors in the neoadjuvant setting. However, systemic delivery of immunotherapies may cause severe immune-related side-effects and hamper the development of combination treatments. Intratumoral delivery of neoadjuvant immunotherapy provides a promising strategy in harnessing the power of immunotherapy while minimizing off-target toxicities.

CPR to the Rescue!: An Interprofessional Pilot Program: Cultivating Practices for Resilience (CPR) Camp.

Purpose/objectives: The hCATS (health Colleges Advancing Team Skills) to CPR (Cultivating Practices for Resilience) Camp was an interprofessional pilot program to promote resilience, introduce strategies for coping with stress, cultivate compassion, and promote work-life balance to prevent burnout among health profession students, faculty, and healthcare professionals who team to provide patient care.

Program Description: The University of Kentucky (UK) College of Nursing received funding to partner with the UK Center for Interprofessional Health Education for immersive weekend activities utilizing KORU and Mindfulness Based Stress Reduction models, conducted by certified UK faculty experts in self-stewardship techniques such as mindfulness practices.

Outcomes: Thirty-nine participants from 7 UK colleges and UK HealthCare participated in 4 distinct CPR Camps, completed program assessments, and created team projects.

Time-dependent cognitive and somatic symptoms of depression as predictors of new cardiac-related events in at-risk patients: the UPBEAT-UK cohort.

Background: Evidence suggests that somatic rather than cognitive depressive symptoms are risk factors for recurrent cardiac events in at-risk patients. However, this has never been explored using a time-dependent approach in a narrow time-frame, allowing a cardiac event-free time-window.

Methods: The analysis was performed on 595 participants [70.

Ipilimumab- and Nivolumab-Induced Colitis Causing Severe Hypokalemia and QTc Prolongation.

Immune-mediated colitis is an uncommon but well-documented adverse event in patients receiving nivolumab or ipilimumab therapy. In this report, we present a 69-year-old man who developed severe hypokalemia and colitis with significant corrected Q-T segment (QTc) prolongation as a result of combination nivolumab-ipilimumab immunotherapy for clear cell renal cell carcinoma.

How can patient-held lists of medication enhance patient safety? A mixed-methods study with a focus on user experience.

Background: Patients often carry medication lists to mitigate information loss across healthcare settings. We aimed to identify mechanisms by which these lists could be used to support safety, key supporting features, and barriers and facilitators to their use.

Methods: We used a mixed-methods design comprising two focus groups with patients and carers, 16 semistructured interviews with healthcare professionals, 60 semistructured interviews with people carrying medication lists, a quantitative features analysis of tools available for patients to record their medicines and usability testing of four tools.

Catalyzing the Hydrodefluorination of CF-Substituted Alkenes by PhSiH. H• Transfer from a Nickel Hydride.

The hydrodefluorination of CF-substituted alkenes can be catalyzed by a nickel(II) hydride bearing a pincer ligand. The catalyst loading can be as low as 1 mol%. -Difluoroalkenes containing a number of functional groups can be formed in good to excellent yields by a radical mechanism initiated by H• transfer from the nickel hydride.

Interprofessional identity development within a brief shadowing experience: An exploratory case study.

The Deans' Interprofessional Honors Colloquium (DIHC) is an honors-level interprofessional elective course that provides a seminar-based forum for students from eleven academic programs to explore the characteristics and implications of collaborative interprofessional practice around a contemporary health topic. This project-based course combines didactic presentations, interactive group learning, and an interprofessional shadowing experience with a corresponding written reflection paper. Ten semesters of Interprofessional Shadowing Reflections (n = 401) were studied via thematic and content analyses to examine the extent to which a brief interprofessional shadowing experience influenced interprofessional identity development.

Short-Term Nitrogen Fertilization Affects Microbial Community Composition and Nitrogen Mineralization Functions in an Agricultural Soil.

Soil extracellular enzymes play a significant role in the N mineralization process. However, few studies have documented the linkage between enzyme activity and the microbial community that performs the function. This study examined the effects of inorganic and organic N fertilization on soil microbial communities and their N mineralization functions over 4 years.

Aromatase (CYP19A1) gene variants, sex steroid levels, and late-life depression.

Background: Sex differences in psychiatric disorders are common and could involve sex steroids. Aromatase, the product of the CYP19A1 gene, is the key enzyme in the conversion of androgen to estrogen. Whether CYP19A1 variants could be associated with depression differently in men and women has not been examined.

Sex-specific depressive symptoms as markers of pre-Alzheimer dementia: findings from the Three-City cohort study.

Late-life depression, as a potential marker of pre-dementia, has seldom been explored by symptom dimension and sex, despite sexual dimorphic differences. This study aimed to examine whether specific depressive dimensions were associated with pre-Alzheimer's disease dementia (pre-AD), separately for women and men. Data were drawn from 5617 (58% women) community-dwellers aged 65+ recruited in 1999-2000 and followed at 2-year intervals for 12 years.

A Comprehensive Resource for Induced Pluripotent Stem Cells from Patients with Primary Tauopathies.

Primary tauopathies are characterized neuropathologically by inclusions containing abnormal forms of the microtubule-associated protein tau (MAPT) and clinically by diverse neuropsychiatric, cognitive, and motor impairments. Autosomal dominant mutations in the MAPT gene cause heterogeneous forms of frontotemporal lobar degeneration with tauopathy (FTLD-Tau). Common and rare variants in the MAPT gene increase the risk for sporadic FTLD-Tau, including progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD).