Bradley Doll

BACKGROUND: Admission avoidance hospital at home provides active treatment by healthcare professionals in the patient's home for a condition that would otherwise require acute hospital inpatient care, and always for a limited time period. This is the fourth update of this review. OBJECTIVES: To determine the effectiveness and cost of managing patients with admission avoidance hospital at home compared with inpatient hospital care. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and CINAHL on 24 February 2022, and checked the reference lists of eligible articles...

PURPOSE: With the results of several recently published clinical trials, this guideline informs on the use of adjuvant radiation therapy (RT) and systemic therapy in the treatment of endometrial cancer. Updated evidence-based recommendations provide indications for adjuvant RT and the associated techniques, the utilization and sequencing of adjuvant systemic therapies, and the effect of surgical staging techniques and molecular tumor profiling. METHODS: The American Society for Radiation Oncology convened a multidisciplinary task force to address 6 key questions that focused on the adjuvant management of patients with endometrial cancer...

The sex hormone estradiol has recently gained attention in human decision-making research. Animal studies have already shown that estradiol promotes dopaminergic transmission and thus supports reward-seeking behavior and aspects of addiction. In humans, natural variations of estradiol across the menstrual cycle modulate the ability to learn from direct performance feedback ("model-free" learning). However, it remains unclear whether estradiol also influences more complex "model-based" contributions to reinforcement learning...

Importance: In hospitals outside of the US Department of Veterans Affairs (VA) system, 1 in 10 percutaneous coronary interventions (PCIs) for stable coronary artery disease is considered rarely appropriate by the appropriate use criteria, with variation across hospitals. The appropriateness of PCIs in VA hospitals has not been documented. Objective: To characterize the appropriateness of PCIs in VA hospitals. Design, Setting, and Participants: This retrospective cohort study included patients with stable coronary artery disease undergoing elective PCI from November 1, 2013, to October 31, 2015, within the VA Clinical Assessment, Reporting, and Tracking Program, an operational program that includes 59 VA hospitals...

Leaffooted bugs ( Leptoglossus spp ; Hemiptera: Coreidae) are phytophagous insects native to the Western Hemisphere. In California, Leptoglossus clypealis and Leptoglossus zonatus are occasional pests on almonds. Early season feeding by L. clypealis and L. zonatus leads to almond drop, while late season feeding results in strikes on kernels, kernel necrosis, and shriveled kernels. A field cage study was conducted to assess feeding damage associated with L. clypealis and L. zonatus on four almond varieties, Nonpareil, Fritz, Monterey, and Carmel...

Stimuli-responsive hydrogels are promising candidates for use in the targeted delivery of drugs using microrobotics. These devices enable the delivery and sustained release of quantities of drugs several times greater than their dry weight and are responsive to external stimuli. However, existing systems have two major drawbacks: (1) severe drug leakage before reaching the targeted areas within the body and (2) impeded locomotion through liquids due to the inherent hydrophilicity of hydrogels. This article outlines an approach to the assembly of hydrogel-based microcapsules in which one device is assembled within another to prevent drug leakage during transport...

The emergence and evolution of new immunological cancer therapies has sparked a rapidly growing interest in discovering novel pathways to treat cancer. Toward this aim, a novel series of pyrrolidine derivatives (compound 5 ) were identified as potent inhibitors of ERK1/2 with excellent kinase selectivity and dual mechanism of action but suffered from poor pharmacokinetics (PK). The challenge of PK was overcome by the discovery of a novel 3( S )-thiomethyl pyrrolidine analog 7 . Lead optimization through focused structure-activity relationship led to the discovery of a clinical candidate MK-8353 suitable for twice daily oral dosing as a potential new cancer therapeutic...

Reducing fumigant emissions is essential for minimizing the environmental impacts of pre-plant soil fumigation. Low permeability plastic films are effective at reducing emissions but have high initial purchase, installation, and disposal costs. The objective of this study was to evaluate if deep fumigant injection and biochar soil amendments can reduce emissions, improve fumigant distribution in soil, and provide acceptable control of plant parasitic nematodes. A pre-plant soil fumigation trial was conducted in a commercial orchard in the San Joaquin Valley, CA, USA...

Compound 5 (SCH772984) was identified as a potent inhibitor of ERK1/2 with excellent selectivity against a panel of kinases (0/231 kinases tested @ 100 nM) and good cell proliferation activity, but suffered from poor PK (rat AUC PK @10 mpk = 0 μM h; F% = 0) which precluded further development. In an effort to identify novel ERK inhibitors with improved PK properties with respect to 5, a systematic exploration of sterics and composition at the 3-position of the pyrrolidine led to the discovery of a novel 3(S)-thiomethyl pyrrolidine analog 28 with vastly improved PK (rat AUC PK @10 mpk = 26 μM h; F% = 70)...

People often perceive configurations rather than the elements they comprise, a bias that may emerge because configurations often predict outcomes. But how does the brain learn to associate configurations with outcomes and how does this learning differ from learning about individual elements? We combined behavior, reinforcement learning models, and functional imaging to understand how people learn to associate configurations of cues with outcomes. We found that configural learning depended on the relative predictive strength of elements versus configurations and was related to both the strength of BOLD activity and patterns of BOLD activity in the hippocampus...

BACKGROUND: Early discharge hospital at home is a service that provides active treatment by healthcare professionals in the patient's home for a condition that otherwise would require acute hospital inpatient care. This is an update of a Cochrane review. OBJECTIVES: To determine the effectiveness and cost of managing patients with early discharge hospital at home compared with inpatient hospital care. SEARCH METHODS: We searched the following databases to 9 January 2017: the Cochrane Effective Practice and Organisation of Care Group (EPOC) register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, CINAHL, and EconLit...

BACKGROUND: Admission avoidance hospital at home provides active treatment by healthcare professionals in the patient's home for a condition that otherwise would require acute hospital inpatient care, and always for a limited time period. This is the third update of the original review. OBJECTIVES: To determine the effectiveness and cost of managing patients with admission avoidance hospital at home compared with inpatient hospital care. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, two other databases, and two trials registers on 2 March 2016...

Socially-conveyed rules and instructions strongly shape expectations and emotions. Yet most neuroscientific studies of learning consider reinforcement history alone, irrespective of knowledge acquired through other means. We examined fear conditioning and reversal in humans to test whether instructed knowledge modulates the neural mechanisms of feedback-driven learning. One group was informed about contingencies and reversals. A second group learned only from reinforcement. We combined quantitative models with functional magnetic resonance imaging and found that instructions induced dissociations in the neural systems of aversive learning...

Evidence increasingly suggests that dopaminergic neurons play a more sophisticated role in predicting rewards than previously thought.

Choosing between smaller prompt rewards and larger later rewards is a common choice problem, and studies widely agree that frontostriatal circuits heavily innervated by dopamine are centrally involved. Understanding how dopamine modulates intertemporal choice has important implications for neurobiological models and for understanding the mechanisms underlying maladaptive decision-making. However, the specific role of dopamine in intertemporal decisions is not well understood. Dopamine may play a role in multiple aspects of intertemporal choices--the valuation of choice outcomes and sensitivity to reward delays...

UNLABELLED: Considerable evidence suggests that multiple learning systems can drive behavior. Choice can proceed reflexively from previous actions and their associated outcomes, as captured by "model-free" learning algorithms, or flexibly from prospective consideration of outcomes that might occur, as captured by "model-based" learning algorithms. However, differential contributions of dopamine to these systems are poorly understood. Dopamine is widely thought to support model-free learning by modulating plasticity in striatum...

OBJECTIVE: Cervical cancer is responsible for more than a quarter of a million deaths globally each year, mostly in developing countries, making therapeutic advances in all health care settings a top priority. The Gynecologic Cancer InterGroup (GCIG) is a worldwide collaboration of leading national research groups that develops and promotes multinational trials in gynecologic cancer. In recognition of the pressing need for action, the GCIG convened an international meeting with expert representation from the GCIG groups and selected large sites in low- and middle-income countries...

Humans learn about people and objects through positive and negative experiences, yet they can also look beyond the immediate reward of an interaction to encode trait-level attributes. We found that perceivers encoded both reward and trait-level information through feedback in an instrumental learning task, but relied more heavily on trait representations in cross-context decisions. Both learning types implicated ventral striatum, but trait learning also recruited a network associated with social impression formation...

Decisions may arise via 'model-free' repetition of previously reinforced actions or by 'model-based' evaluation, which is widely thought to follow from prospective anticipation of action consequences using a learned map or model. While choices and neural correlates of decision variables sometimes reflect knowledge of their consequences, it remains unclear whether this actually arises from prospective evaluation. Using functional magnetic resonance imaging and a sequential reward-learning task in which paths contained decodable object categories, we found that humans' model-based choices were associated with neural signatures of future paths observed at decision time, suggesting a prospective mechanism for choice...

Throughout our lives, we face the important task of distinguishing rewarding actions from those that are best avoided. Importantly, there are multiple means by which we acquire this information. Through trial and error, we use experiential feedback to evaluate our actions. We also learn which actions are advantageous through explicit instruction from others. Here, we examined whether the influence of these two forms of learning on choice changes across development by placing instruction and experience in competition in a probabilistic-learning task...