Effects of Testing and Disclosing Ancestry-Specific Genetic Risk for Kidney Failure on Patients and Health Care Professionals: A Randomized Clinical Trial.

Importance: Risk variants in the apolipoprotein L1 (APOL1 [OMIM 603743]) gene on chromosome 22 are common in individuals of West African ancestry and confer increased risk of kidney failure for people with African ancestry and hypertension. Whether disclosing APOL1 genetic testing results to patients of African ancestry and their clinicians affects blood pressure, kidney disease screening, or patient behaviors is unknown.

Objective: To determine the effects of testing and disclosing APOL1 genetic results to patients of African ancestry with hypertension and their clinicians.

The role of tropical volcanic eruptions in exacerbating Indian droughts.

The Indian summer monsoon rainfall (ISMR) is vital for the livelihood of millions of people in the Indian region; droughts caused by monsoon failures often resulted in famines. Large volcanic eruptions have been linked with reductions in ISMR, but the responsible mechanisms remain unclear. Here, using 145-year (1871-2016) records of volcanic eruptions and ISMR, we show that ISMR deficits prevail for two years after moderate and large (VEI > 3) tropical volcanic eruptions; this is not the case for extra-tropical eruptions.

Elevated aerosol layer over South Asia worsens the Indian droughts.

Droughts have become more severe and recurrent over the Indian sub-continent during the second half of the twentieth century, leading to more severe hydro-climatic and socio-economic impacts over one of the most densely populated parts of the world. So far, droughts have mostly been connected to circulation changes concomitant with the abnormal warming over the Pacific Ocean, prevalently known as "El Niño". Here, exploiting observational data sets and a series of dedicated sensitivity experiments, we show that the severity of droughts during El Niño is amplified (17%) by changes in aerosols.

Successful recruitment and retention of diverse participants in a genomics clinical trial: a good invitation to a great party.

Purpose: African ancestry (AA) individuals are inadequately included in translational genomics research, limiting generalizability of findings and benefits of genomic discoveries for populations already facing disproportionately poor health outcomes. We aimed to determine the impact of stakeholder-engaged strategies on recruitment and retention of AA adult patients into a clinical trial testing them for renal risk variants nearly exclusive to AAs.

Methods: Our academic-clinical-community team developed ten key strategies that recognize AAs' barriers and facilitators for participation.

Decline and poleward shift in Indian summer monsoon synoptic activity in a warming climate.

Cyclonic atmospheric vortices of varying intensity, collectively known as low-pressure systems (LPS), travel northwest across central India and produce more than half of the precipitation received by that fertile region and its ∼600 million inhabitants. Yet, future changes in LPS activity are poorly understood, due in part to inadequate representation of these storms in current climate models. Using a high-resolution atmospheric general circulation model that realistically simulates the genesis distribution of LPS, here we show that Indian monsoon LPS activity declines about 45% by the late 21st century in simulations of a business-as-usual emission scenario.

Race, Genomics and Chronic Disease: What Patients with African Ancestry Have to Say.

Background: Variants of the APOL1 gene increase risk for kidney failure 10-fold, and are nearly exclusively found in people with African ancestry. To translate genomic discoveries into practice, we gathered information about effects and challenges incorporating genetic risk in clinical care.

Methods: An academic-community-clinical team tested 26 adults with self-reported African ancestry for APOL1 variants, conducting in-depth interviews about patients' beliefs and attitudes toward genetic testing- before, immediately, and 30 days after receiving test results.

Determining the effects and challenges of incorporating genetic testing into primary care management of hypertensive patients with African ancestry.

People of African ancestry (Blacks) have increased risk of kidney failure due to numerous socioeconomic, environmental, and clinical factors. Two variants in the APOL1 gene are now thought to account for much of the racial disparity associated with hypertensive kidney failure in Blacks. However, this knowledge has not been translated into clinical care to help improve patient outcomes and address disparities.

De Novo Headache During Pregnancy and Puerperium.

Background: A conservative estimate is that approximately 5% of pregnancies are affected by de novo headache, that is, new-onset or new-type headache.

Objectives: (1) Summarize the available literature, which is exclusively neurological, regarding de novo headache during the third trimester of pregnancy and puerperium; and (2) review the common pathologies of pregnancy and puerperium that may be relevant to de novo headache, with focus on the first and second trimester. We obtained the literature through a search of PubMed and references of the retrieved publications, without time limit.

Improving the Advance Directive Request and Retrieval Process in Critical Access Hospitals: Honoring the Patient's Wishes.

The Patient Self-Determination Act was created to enhance awareness and use of advance directives. Several states also have created registries where the advance directives can be easily retrieved when needed. Quick retrieval is especially important in critical access hospitals where patients are often transferred to other facilities.

Impacts of the ENSO Modoki and other Tropical Indo-Pacific Climate-Drivers on African Rainfall.

The study diagnoses the relative impacts of the four known tropical Indo-Pacific drivers, namely, El Niño Southern Oscillation (ENSO), ENSO Modoki, Indian Ocean Dipole (IOD), and Indian Ocean Basin-wide mode (IOBM) on African seasonal rainfall variability. The canonical El Niño and El Niño Modoki are in general associated with anomalous reduction (enhancement) of rainfall in southern (northern) hemispheric regions during March-May season. However, both the El Niño flavours anomalously reduce the northern hemispheric rainfall during June-September.

A Quantitative Process for Enhancing End of Phase 2 Decisions.

The objectives of the phase 2 stage in a drug development program are to evaluate the safety and tolerability of different doses, select a promising dose range, and look for early signs of activity. At the end of phase 2, a decision to initiate phase 3 studies is made that involves the commitment of considerable resources. This multifactorial decision, generally made by balancing the current condition of a development organization's portfolio, the future cost of development, the competitive landscape, and the expected safety and efficacy benefits of a new therapy, needs to be a good one.

A randomized phase 2 study of paclitaxel and carboplatin with or without conatumumab for first-line treatment of advanced non-small-cell lung cancer.

Introduction: This study evaluated the efficacy, safety, and pharmacokinetics of conatumumab combined with paclitaxel-carboplatin (PC) as first-line treatment for advanced non-small-cell lung cancer (NSCLC).

Methods: Patients (aged >18 years) with previously untreated advanced or recurrent NSCLC were randomized 1:1:1 (stratified by Eastern Cooperative Oncology Group performance status and disease stage) to receive up to six 3-week cycles of PC combined with conatumumab (arm 1, 3 mg/kg; arm 2, 15 mg/kg) or placebo (arm 3) every 3 weeks. The primary endpoint was progression-free survival (PFS).

Implementation of the Department of Veterans Affairs' first point-of-care clinical trial.

Objectives: The Massachusetts Veterans Epidemiology Research and Information Center in collaboration with the Stanford Center for Innovative Study Design set out to test the feasibility of a new method of evidence generation. The first pilot of a point-of-care clinical trial (POCCT), adding randomization and other study processes to an electronic medical record (EMR) system, was launched to compare the effectiveness of two insulin regimens.

Materials And Methods: Existing functionalities of the Veterans Affairs (VA) computerized patient record system (CPRS)/veterans health information systems and technology architecture (VISTA) were modified to support the activities of a randomized controlled trial including enrolment, randomization, and longitudinal data collection.

Health-related quality of life assessment using St. George's respiratory questionnaire in asthmatics on inhaled corticosteroids.

Context: Chronic diseases like asthma have significant effects on patients' health-related quality of life (HRQoL). HRQoL measures additional indices as compared to objective measurements like spirometry.

Aims: To assess and compare disease-specific quality of life in asthma patients using St.

A statistician's perspective on biomarkers in drug development.

Biomarkers play an increasingly important role in many aspects of pharmaceutical discovery and development, including personalized medicine and the assessment of safety data, with heavy reliance being placed on their delivery. Statisticians have a fundamental role to play in ensuring that biomarkers and the data they generate are used appropriately and to address relevant objectives such as the estimation of biological effects or the forecast of outcomes so that claims of predictivity or surrogacy are only made based upon sound scientific arguments. This includes ensuring that studies are designed to answer specific and pertinent questions, that the analyses performed account for all levels and sources of variability and that the conclusions drawn are robust in the presence of multiplicity and confounding factors, especially as many biomarkers are multidimensional or may be an indirect measure of the clinical outcome.

A point-of-care clinical trial comparing insulin administered using a sliding scale versus a weight-based regimen.

Background: Clinical trials are widely considered the gold standard in comparative effectiveness research (CER) but the high cost and complexity of traditional trials and concerns about generalizability to broad patient populations and general clinical practice limit their appeal. Unsuccessful implementation of CER results limits the value of even the highest quality trials. Planning for a trial comparing two standard strategies of insulin administration for hospitalized patients led us to develop a new method for a clinical trial designed to be embedded directly into the clinical care setting thereby lowering the cost, increasing the pragmatic nature of the overall trial, strengthening implementation, and creating an integrated environment of research-based care.

Yeast screens identify the RNA polymerase II CTD and SPT5 as relevant targets of BRCA1 interaction.

BRCA1 has been implicated in numerous DNA repair pathways that maintain genome integrity, however the function responsible for its tumor suppressor activity in breast cancer remains obscure. To identify the most highly conserved of the many BRCA1 functions, we screened the evolutionarily distant eukaryote Saccharomyces cerevisiae for mutants that suppressed the G1 checkpoint arrest and lethality induced following heterologous BRCA1 expression. A genome-wide screen in the diploid deletion collection combined with a screen of ionizing radiation sensitive gene deletions identified mutants that permit growth in the presence of BRCA1.

An approach to chronic fatigue syndrome in adults.

Background: The neurologist is often asked to evaluate patients with a chief complaint of fatigue. Many neurologists do not believe in the pathologically based disease known as chronic fatigue syndrome, yet as a group, neurologists are well suited to guide the diagnostic work up of such patients to pinpoint treatable disorders in the realm of neurology, general medicine, and psychiatry.

Review Summary: Every patient should be carefully evaluated for certain medical, psychiatric, and neurologic disease that can cause fatigue as the most prominent symptom.

Transcutaneous access to retrograde axonal flow.

Transcutaneous entry of fluorescent tracer and subsequent retrograde neuronal transport achieved by the use of dimethyl sulfoxide (DMSO) as a vehicle fluorescent dye dissolved in DMSO and applied topically to the hind limb of rats was found in corresponding dorsal root ganglia; aqueous absorption of tracer dye by neuronal tissue was not demonstrated. This example of transcutaneous access and retrograde transport may have implications as to the entry of various toxins, viruses, chemicals, and therapeutic agents to the nervous system.

Improvement in the polyneuropathy associated with familial amyloid polyneuropathy after liver transplantation.

Objective: To study, following liver transplantation, the neurologic progression or regression of the polyneuropathy in a cohort of patients with familial amyloidotic polyneuropathy (FAP).

Background: FAP is characterized by the relentless progression of neurologic and cardiac impairment, leading to death within 7 to 15 years after disease onset. No effective treatment to slow or halt the progression of this disease has been found to date.

Alpha Interferon in AIDS-Related Progressive Multifocal Leukoencephalopathy.

Objective: To determine the efficacy of recombinant interferon alpha in the treatment of progressive multifocal leukoencephalopathy associated with the acquired immunodeficiency syndrome (AIDS).

Design: Open label, uncontrolled study.

Setting: Neurological unit and clinical AIDS program, Boston City Hospital, Boston, MA.