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The numbers are stark: According to the Heart Disease and Stroke Statistics 2021 Update, compiled each year by the American Heart Association (AHA) and the National Institutes of Health, cardiovascular [...]

With the death of Alexei Navalny, Vladimir Kara-Murza--the crusading and imprisoned Russian journalist--is now the public face of dissent and most prominent democratic opponent of Vladimir Putin's dictatorship. This is [...]

The most influential account of phasic dopamine holds that it reports reward prediction errors (RPEs). The RPE-based interpretation of dopamine signaling is, in its original form, probably too simple and fails to explain all the properties of phasic dopamine observed in behaving animals. This Perspective helps to resolve some of the conflicting interpretations of dopamine that currently exist in the literature. We focus on the following three empirical challenges to the RPE theory of dopamine: why does dopamine (1) ramp up as animals approach rewards, (2) respond to sensory and motor features and (3) influence action selection? We argue that the prediction error concept, once it has been suitably modified and generalized based on an analysis of each computational problem, answers each challenge. Nonetheless, there are a number of additional empirical findings that appear to demand fundamentally different theoretical explanations beyond encoding RPE. Therefore, looking forward, we discuss the prospects for a unifying theory that respects the diversity of dopamine signaling and function as well as the complex circuitry that both underlies and responds to dopaminergic transmission.

The CDC estimates that from October 1, 2019, to April 4, 2020, there have been 410,000 to 740,000 hospitalizations and 24,000 to 62,000 deaths related to influenza in the United [...]

Clinical decision-making is contingent on high-quality evidence that informs patients as well as physicians about the effectiveness and trade-offs of different therapies. Well-designed, randomized clinical trials are atop 'the pyramid [...]

This article is a semiannual review of recent developments in the area of individual federal taxation. It covers cases, rulings, and guidance issued to explain the law known as the [...]

There are a variety of medications being studied for the COVID-19, and the possible treatment landscape is rapidly evolving. There are no FDA-approved medications for the treatment of COVID-19. Currently, [...]

Background: The optimal management of node-positive (pN1) prostate cancer following radical prostatectomy (RP) remains uncertain. Despite randomized evidence, utilization of immediate, life-long androgen deprivation therapy (ADT) remains poor, and recent trials of early salvage radiotherapy included only a minority of pN1 patients. We therefore emulated a hypothetical pragmatic trial of adjuvant radiotherapy versus observation in men with pN1 prostate cancer. Methods: Using the RADICALS-RT trial to inform the design of a hypothetical trial, we identified men aged 50-69 years with pT2-3 Rany pN1 M0, pre-treatment PSA < 50 ng/mL prostate cancer in the NCDB from 2006 to 2015 treated with 60–72 Gy of adjuvant RT (aRT) ± ADT within 26 weeks of RP or observation. After estimating a propensity score for receipt of aRT, we estimated absolute and relative treatment effects using stabilized inverse probability of treatment (sIPW) re-weighting. Results: In total, 3510 patients were included in the study, of whom 587 (17%) received aRT (73% with concurrent ADT). Median follow-up was 40.0 -months, during which 333 deaths occurred. After sIPW re-weighting, baseline characteristics were well-balanced. Adjusted overall survival (OS) was 93% versus 89% at 5-years and 82% versus 79% at 7-years for aRT versus observation (p= 0.11). In IPW-reweighted Cox regression, aRT was associated with a lower risk of all-cause mortality (ACM) than observation, but this did not reach statistical significance (HR 0.70 p= 0.06). In analyses examining heterogeneity of treatment effects, aRT was associated with improved ACM only for men with Gleason 8–10 disease (HR 0.59, p= 0.01), ≥2 positive LNs (HR 0.49, p= 0.04 for 2 positive LNs; HR 0.42, p= 0.01 for ≥3 positive LNs), or negative surgical margins (HR 0.50, p= 0.02). Conclusions: In observational analyses designed to emulate a hypothetical target trial of aRT versus observation in pN1 prostate cancer, aRT was associated with improved OS only for men with Gleason 8–10 disease, ≥2 positive LNs, or negative surgical margins.

This article is a semiannual review of recent developments in the area of individual federal taxation. It analyzes several hobby loss cases, cases on qualifying as real estate professionals, and [...]

According to the Centers for Disease Control and Prevention (CDC), at least 2 million individuals are infected with antibiotic-resistant bacteria annually, resulting in more than 23,000 deaths. Antimicrobial stewardship programs [...]

Hospital health systems benefit greatly from pharmacists in terms of quality, safety, and value. The value of the pharmacist is further demonstrated by linking clinical activities with patient and financial [...]

Humanity has a shrinking window to drastically reduce greenhouse gas emissions, yet climate action is still lacking on both individual and policy levels. We argue that this is because behavioral interventions have largely neglected the basic principles of operant conditioning as one set of tools to promote collective climate action. In this perspective, we propose an operant conditioning framework that uses rewards and punishments to shape transportation, food, waste, housing, and civic actions. This framework highlights the value of reinforcement in encouraging the switch to low-emission behavior, while also considering the benefit of decreasing high-emission behavior to expedite the transition. This approach also helps explain positive and negative spillovers from behavioral interventions. This paper provides a recipe to design individual-level and system-level interventions to generate and sustain low-emission behavior to help achieve net zero emissions.

Background: Although active surveillance is the preferred management for low-risk prostate cancer (PCa), some men remain at risk of overtreatment with definitive local therapy. We hypothesized that baseline characteristics may be associated with overtreatment and represent a potential source of health disparities. We therefore examined the associations of patient and disease characteristics with the surgical overtreatment of low-risk PCa. Methods: We identified men aged 45–75 years with cT1 cN0 cM0 prostate adenocarcinoma with biopsy Gleason score 6 and PSA < 10 ng/ml from 2010–2016 in the National Cancer Database (NCDB) and who underwent radical prostatectomy (RP). We evaluated the associations of baseline characteristics with clinically insignificant PCa (iPCa) at RP (i.e., “overtreatment”), defined as organ-confined (i.e., pT2) Gleason 3 + 3 disease, using multivariable logistic regression. Results: We identified 36,088 men with low-risk PCa who underwent RP. The unadjusted rate of iPCa decreased during the study period, from 54.7% in 2010 to 40.0% in 2016. In multivariable analyses adjusting for baseline characteristics, older age (OR 0.98, 95% CI 0.97–0.98), later year of diagnosis (OR 0.62, 95% CI 0.57–0.67 for 2016 vs. 2010), Black race (OR 0.85, 95% CI 0.79–0.91), treatment at an academic/research program (OR 0.82, 95% CI 0.73–0.91), higher PSA (OR 0.91, 95% CI 0.90–0.92), and higher number of positive biopsy cores (OR 0.87, 95% CI 0.86–0.88) were independently associated with a lower risk of overtreatment (iPCa) at RP. Conversely, a greater number of biopsy cores sampled (OR 1.01, 95% CI 1.01–1.02) was independently associated with an increased risk of overtreatment (iPCa) at RP. Conclusions: We observed an ~27% reduction in rates of overtreatment of men with low-risk PCa over the study period. Several patient, disease, and structural characteristics are associated with detection of iPCa at RP and can inform the management of men with low-risk PCa to reduce potential overtreatment.

Osteoarthritis (OA) is the most common form of arthritis, afecting more than 32.5 million adults in the United States. (1) Although there is no cure for this degenerative joint disease, [...]

PREVIEW * The IRS issued proposed regulations that update the definition of dependent in the regulations to reflect changes made to Sec. 152. * The Tax Court held that donee [...]

EXECUTIVE SUMMARY * Proposed regulations would eliminate the requirement to include a copy of a Sec. 83(b) election with a taxpayer's return. * The IRS issued final regulations that provide [...]

The Biologics Price Competition and Innovation Act (BPCI Act) of 2009 created an abbreviated licensure pathway for biological products that are demonstrated to be interchangeable with an FDA approved biological [...]

More than 7.5 million individuals in the United States have psoriasis, according to the National Psoriasis Foundation (NPF). (1) Psoriasis is a chronic, inflammatory autoimmune disease characterized by raised, red, [...]

I. INTRODUCTION Prosecutors enjoy a broad array of opportunities to communicate with the public outside the courtroom. Justice Holmes's famous dictum--that "[t]he theory of our system is that the conclusions [...]

EXECUTIVE SUMMARY * The IRS announced that payments for identity theft protection services could be excluded from gross income if received after a data breach. * The Ninth Circuit reversed [...]

Pharmacists can play an important role in educating patients with certain autoimmune diseases about strategies to prevent a temporary worsening of symptoms in hot or humid weather. More than 80 [...]

Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes joint pain, stiffness, swelling, and decreased joint movement. (1) Pharmacists are well equipped to help patients select the most appropriate [...]

Multiple sclerosis (MS) is a disease of the central nervous system (CNS) that affects almost l million individuals in the United States, according to the National Multiple Sclerosis Society. (12) [...]

It's been said that 'decisions are made by those who show up.' As Indianapolis business leaders, we are obliged to show up for equity and inclusion, against policies that make [...]

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of morbidity and mortality, both globally and in individuals with type 2 diabetes (T2D). (1) Individuals with diabetes are at greater risk [...]

According to the FDA, 53 new drugs received approval in 2020. (1) As the coronavirus disease 2019 (COVID-19) pandemic persists throughout the United States, the FDA is focusing on treatment [...]

October is Breast Cancer Awareness Month, and it is important to educate patients about early detection, treatment, and pain management strategies for the second-most-common cancer in women in the US. [...]

Vaccines are crucial to protect public health globally, and pharmacists can play an important role in educating patients on the importance of immunizations. The World Health Organization named vaccine hesitancy [...]

Investigators are evaluating a variety of medications for the novel coronavirus disease 2019 (COVID-19), and the possible treatment landscape is rapidly evolving. There are no FDA-approved medications for the treatment [...]

According to the National Diabetes Statistics Report, 34.2 million Americans are living with diabetes. (1) With new drugs and technologies available, pharmacists are at the forefront of the effort to [...]

Cancer is not quite the ferocious killer that it used to be. Millions of Americans are living with cancer, not just dying from it. Reasons for the diminishing death rate [...]

Cheers to 2022. There's no doubt that the upcoming year will be filled with many exciting opportunities for pharmacy owners. Independent pharmacies have played an important role during the COVID-19 [...]

It was the summer before my second year of teaching and I had been looking forward to this day for months. Eager to fill my students' folders with new music [...]

The COVID-19 pandemic has brought many changes to the pharmacy profession. Because pharmacists are one of the most accessible health care professionals, they play an integral role in patient care [...]

Pharmacists can play a key role in treating patients with ovarian cancer through counseling, drug information consults, and adherence. September is Ovarian Cancer Awareness Month and an important time to [...]

Hummingbirds are very well adapted to sustain efficient and rapid metabolic shifts. They oxidize ingested nectar to directly fuel flight when foraging but have to switch to oxidizing stored lipids derived from ingested sugars during the night or long-distance migratory flights. Understanding how this organism moderates energy turnover is hampered by a lack of information regarding how relevant enzymes differ in sequence, expression, and regulation. To explore these questions, we generated a chromosome-scale genome assembly of the ruby-throated hummingbird (A. colubris) using a combination of long- and short-read sequencing, scaffolding it using existing assemblies. We then used hybrid long- and short-read RNA sequencing of liver and muscle tissue in fasted and fed metabolic states for a comprehensive transcriptome assembly and annotation. Our genomic and transcriptomic data found positive selection of key metabolic genes in nectivorous avian species and deletion of critical genes (SLC2A4, GCK) involved in glucostasis in other vertebrates. We found expression of a fructose-specific version of SLC2A5putatively in place of insulin-sensitive SLC2A5, with predicted protein models suggesting affinity for both fructose and glucose. Alternative isoforms may even act to sequester fructose to preclude limitations from transport in metabolism. Finally, we identified differentially expressed genes from fasted and fed hummingbirds, suggesting key pathways for the rapid metabolic switch hummingbirds undergo.

The human Y chromosome has been notoriously difficult to sequence and assemble because of its complex repeat structure that includes long palindromes, tandem repeats and segmental duplications1–3. As a result, more than half of the Y chromosome is missing from the GRCh38 reference sequence and it remains the last human chromosome to be finished4,5. Here, the Telomere-to-Telomere (T2T) consortium presents the complete 62,460,029-base-pair sequence of a human Y chromosome from the HG002 genome (T2T-Y) that corrects multiple errors in GRCh38-Y and adds over 30 million base pairs of sequence to the reference, showing the complete ampliconic structures of gene families TSPY, DAZand RBMY; 41 additional protein-coding genes, mostly from the TSPYfamily; and an alternating pattern of human satellite 1 and 3 blocks in the heterochromatic Yq12 region. We have combined T2T-Y with a previous assembly of the CHM13 genome4and mapped available population variation, clinical variants and functional genomics data to produce a complete and comprehensive reference sequence for all 24 human chromosomes.

BACKGROUND: Survival with locally advanced bladder cancer (LABC) following radical cystectomy (RC) remains poor. Although adjuvant chemotherapy (AC) is standard of care, one small, randomized trial has suggested a potential survival benefit when combined with post-operative radiotherapy (PORT).OBJECTIVE: We examined the association of AC + PORT with overall survival (OS) in patients with LABC after RC.METHODS: Using a prior phase 2 trial to inform design, we conducted observational analyses to emulate a hypothetical target trial of patients aged 18–79 years with pT3-4 Nany M0 or pTany N1-3 M0 urothelial bladder carcinoma following RC who were treated with AC (multiagent chemotherapy within 3 months of RC) with or without PORT (≥45 Gy to the pelvis) from 2006–2015 in the NCDB. Patients who received preoperative chemotherapy or radiotherapy were excluded. The associations of treatment with OS were evaluated using multivariable Cox regression.RESULTS: 1,684 patients were included, with 66 receiving AC + PORT and 1,618 AC alone. Compared to patients treated with AC alone, those treated with AC + PORT were more likely to have pT4 disease (52% vs 26%; p< 0.01), positive surgical margins (44% vs 17%; p< 0.01), and be treated at a non-academic facility (75% vs 53%; p< 0.01). Crude 5-year OS was 19% for AC + PORT versus 36% for AC alone (p= 0.01). Adjusted 5-year OS was 33% for AC + PORT versus 36% for AC alone (p= 0.49). After adjusting for baseline characteristics including pathologic features, AC + PORT was not associated with improved OS compared to AC alone (HR 1.11; 95% CI 0.82–1.51).CONCLUSIONS: Although infrequently utilized, the addition of radiotherapy to AC is not associated with improved OS in LABC. These results highlight the need for prospective trials to better define the potential benefits from PORT with regard to symptomatic progression and oncologic outcomes.

Irritable bowel syndrome (IBS) is a chronic condition that affects the large intestine and can have an impact on patients' quality of life. (1) Treatment typically consists of dietary changes, [...]

This article covers recent developments affecting individual taxation. The items are arranged in Code section order. Sec. 1: Tax Imposed Notice 2011-64, (1) which amplifies and supersedes Notice 2006-101, (2) [...]

This article covers developments from the past year affecting taxation of individuals, including last year's tax relief, health care, and small business legislation, regulations, cases, and IRS guidance. The items [...]

This article covers recent developments affecting taxation of individuals, including last year's tax relief and small business legislation, regulations, cases, and IRS guidance. The items are arranged in Code section [...]

Pharmacists have an important responsibility not only to keep up with new drug approvals but also to stay abreast of the latest pharmacy regulations affecting the profession. The Oath of [...]

According to the FDA, 48 drugs have been approved in 2019, bringing more treatment options to the market for patients. (1) Vizient, a health care performance improvement company, released its [...]

This article covers recent developments affecting taxation of individuals, including the health care reform and other legislation, regulations, cases, and IRS guidance. The items are arranged in Code section order. [...]