Drug discovery strategies for acute radiation syndrome

Introduction: There are at the minimum two major, quite different approaches to advance drug discovery. The first being the target-based drug discovery (TBDD) approach that is commonly referred to as the molecular approach. The second approach is the phenotype-based drug discovery (PBDD), also known as physiology-based drug discovery or empirical approach.

Area covered: The authors discuss, herein, the need for developing radiation countermeasure agents for various sub-syndromes of acute radiation syndromes (ARS) following TBDD and PBDD approaches. With time and continuous advances in radiation countermeasure drug development research, the expectation is to have multiple radiation countermeasure agents for each sub-syndrome made available to radiation exposed victims.

Expert opinion: The majority of the countermeasures currently being developed for ARS employ the PBDD approach, while the TBDD approach is clearly under-utilized. In the future, an improved drug development strategy might be a ‘hybrid’ strategy that is more reliant on TBDD for the initial drug discovery via large-scale screening of potential candidate agents, while utilizing PBDD for secondary screening of those candidates, followed by tertiary analytics phase in order to pinpoint efficacious candidates that target the specific sub-syndromes of ARS.     

US Food and Drug Administration approvals for Bruton tyrosine kinase inhibitors in patients with chronic lymphocytic leukemia: Potential inefficiencies in trial design and evidence generation

The US Food and Drug Administration granted acalabrutinib approval as the second Bruton tyrosine kinase (BTK) inhibitor to treat patients with chronic lymphocytic leukemia and small lymphocytic lymphoma as monotherapy or in combination with obinutuzumab. This approval was based on 2 phase 3 trials: ELEVATE-TN and ASCEND. There are several concerns with the design of these trials, including suboptimal treatment of patients in the control arm, expansion of the trial population, and lack of data regarding efficacy or tolerability compared with ibrutinib, a first-in-class drug. The Food and Drug Administration approval of acalabrutinib for patients with chronic lymphocytic leukemia and small lymphocytic lymphoma represents concerning drug approval patterns in the United States and a weakness in evidence generation.     

A decline in prosocial language helps explain public disapproval of the US Congress

Talking about helping others makes a person seem warm and leads to social approval. This work examines the real world consequences of this basic, social-cognitive phenomenon by examining whether record-low levels of public approval of the US Congress may, in part, be a product of declining use of prosocial language during Congressional debates. A text analysis of all 124 million words spoken in the House of Representatives between 1996 and 2014 found that declining levels of prosocial language strongly predicted public disapproval of Congress 6 mo later. Warm, prosocial language still predicted public approval when removing the effects of societal and global factors (e.g., the September 11 attacks) and Congressional efficacy (e.g., passing bills), suggesting that prosocial language has an independent, direct effect on social approval.As recently as 2002, public approval of Congress was reliably over 50% and as high as 84%. In late 2013, though, public approval reached an all-time low, with less than 10% of Americans expressing support (1). What caused this dramatic decline in public approval in just over a decade? One explanation is that the public held Congress responsible for societal and global problems (e.g., a weak economy) (2, 3). A second explanation is that the public disapproves of ineffective governance. For example, public approval of Congress tends to drop when Republicans and Democrats are polarized against one another and when Congress conflicts with the President (4, 5). We test a third explanation that has less to do with action and more to do with talk (6). We suggest that recent public disapproval partly resulted from the disappearance of warm, prosocial language in Congressional discourse.Previous experimental research has shown that presenting a warm and prosocial demeanor increases social approval (7). People reveal a wealth of information about their feelings and intentions through verbal communication (8–10). The speaker’s underlying motives notwithstanding, talking about helping others makes positive impressions upon an audience (11). We investigated whether this well-documented finding can explain public perceptions of Congress. Specifically, we asked whether the recent rise of public disapproval of Congress is predicted by declining prosocial language of elected representatives.To measure prosocial language, we computer analyzed all 123,927,807 words spoken in session of the US House of Representatives between 1996 and 2014. Our approach was to look for linguistic markers of prosocial language; we used content analysis software (12) to calculate the proportion of words in the target text that matched entries in a validated dictionary of prosocial words (13). We then compared levels of prosocial language within each month of Congress with their approval ratings by the American public (14) and found a striking match. Fig. 1 shows that levels of prosocial language and the public’s approval followed the same trajectory between 1996 and 2014, r(204) = 0.55, P < 0.001. Notably, the language of both Democrats, r(204) = 0.53, P < 0.001, and Republicans, r(204) = 0.54, P < 0.001, predicted the public’s approval of Congress.Open in a separate windowFig. 1.Prosocial language within the US Congress predicts the public’s approval of Congress. (A) Prosocial language represents the density of prosocial words in the in-session speeches of members of the US House of Representatives. (B) Public approval is Gallup survey data. Individual data points represent monthly scores. Solid lines connect 2-y session means.Public approval peaked in the aftermath of the September 11 attacks, declined over the next 7 y, rose slightly in the wake of the 2008 financial crisis, and then declined again. Prosocial language followed a nearly identical trajectory. In the years spanning 2002 and 2014, a small (19%) decrease in prosocial language ushered in a large (75%) decrease in public approval. The individual words whose use most strongly predicted public approval were as follows: gentle, involve, educate, contribute, concerned, give, tolerate, trust, and cooperate.The correlation between prosocial language and public approval does not necessarily imply that representatives’ language caused the public to approve of them. The reverse could be true: The public’s approval could cause changes in the topics that representatives raised. If one variable were causing the other, the causal factor would have changed first and the effected factor second. We tested which variable changed first in time by assessing the association between prosocial language in the present and public approval with time lags of up to 50 mo in the past and future (Fig. 2). The distribution of the associations across the time lags nearly perfectly fitted a normal distribution curve, r(98) = 0.97, P < 0.001. The maximum association between prosocial language and public approval was at +6.7 mo, meaning that what Congress says today best predicts their public approval ratings 29 wk into the future.Open in a separate windowFig. 2.Time-lagged associations between prosocial language and public approval of the US Congress. How representatives speak today best predicts their public approval ratings 6.7 mo into the future.Another concern with the present data is the possibility that some exogenous factor (e.g., the September 11 attacks) caused changes in both language and public approval. We reasoned that, if operative, societal and global factors would also have influenced the US President’s language and/or the economy. Alternatively, dysfunctional governance may cause both politicians’ rhetoric to be less civil and the public to disapprove (SI Text and Table S1). To test whether prosocial language has an independent, direct effect on the public sentiment, we ran a regression analysis in which we controlled for the effects of both societal/global factors (in the form of the President’s prosocial language, US unemployment rate, and US consumer expectations about the economy) and competent governance (in the form of partisan conflict, the number of bills that Congress passed, and Presidential vetoes). Even with these conservative controls, prosocial language within Congress still predicted the public’s approval (

Implementation and outcomes of hospital-wide computerized antimicrobial approval system and on-the-spot education in a traumatic intensive care unit in Taiwan

Background/purpose

Inappropriate prescribing of antibiotics is a major health-care problem in intensive care units (ICUs). This study evaluates the impact of a direct hospital-wide computerized antimicrobial approval system (HCAAS) and on-the-spot education for practitioners in a neurosurgical ICU in Taiwan.

Parent–student communication regarding alcohol use: an examination of tacit approval

Background: First-year college students appear to be at particular risk for experiencing negative alcohol-related consequences. This risk has fostered a need to identify malleable factors associated with first-year student alcohol consumption. Studies have shown significant positive associations between perceived parental approval of drinking and alcohol use and associated consequences. However, researchers have not yet identified the exact mechanism responsible for this relationship.

Objectives: This study examined a potential vehicle by which parents may communicate approval of drinking to their college aged children. Specifically, we tested if less parent communication about alcohol use would be perceived as tacit approval on the part of first-year college students.

Methods: Two hundred seventy-nine first-year undergraduate students age 18–20 answered online surveys of perceived parental approval of drinking, negative alcohol-related consequences, perceived parental knowledge, and parent–student communication regarding alcohol use.

Results: Contrary to hypothesis, our findings indicate the amount of parent–student communication regarding alcohol use did not predict perceived parental approval of drinking in first-year students, after controlling for the influence of gender, perceived parental knowledge, and negative consequences of alcohol use.

Conclusions: Results suggest that first-year college students may not interpret less parent–student communication regarding alcohol as tacit approval of drinking.     

我国人类遗传资源国际合作现状及管理对策

系统分析2018年我国人类遗传资源国际合作项目申请和批准情况，得出获批项目的研究热点、单位及地区分布。针对现状提出相关建议，包括促进事中事后监督检查常态化，推进法律宣贯和民众科普，促进国家临床医学研究中心国际合作等，供相关决策部门研究人员参考。