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To describe the development, implementation, and assessment of an internal medicine introductory pharmacy practice experience (IPPE) that was integrated with an existing advanced pharmacy practice experience (APPE) in internal medicine. A structured IPPE was designed for first-, second-, and third-year pharmacy (P1, P2, and P3) students. Activities for the IPPE were based on the established APPE and the individual learner's educational level. Students reported a greater understanding of clinical pharmacists’ roles, increased confidence in their clinical skills, and better preparation for APPEs. Peers viewed the approach as innovative and transferable to other practice settings. Participating faculty members provided a greater number of contact hours compared to traditional one-time site visits. Integrating an IPPE with an existing APPE is an effective and efficient way to provide patient care experiences for students in the P1-P3 years in accordance with accreditation standards.

To describe the development, implementation, and assessment of an internal medicine introductory pharmacy practice experience (IPPE) that was integrated with an existing advanced pharmacy practice experience (APPE) in internal medicine. A structured IPPE was designed for first-, second-, and third-year pharmacy (P1, P2, and P3) students. Activities for the IPPE were based on the established APPE and the individual learner's educational level. Students reported a greater understanding of clinical pharmacists' roles, increased confidence in their clinical skills, and better preparation for APPEs. Peers viewed the approach as innovative and transferable to other practice settings. Participating faculty members provided a greater number of contact hours compared to traditional one-time site visits. Integrating an IPPE with an existing APPE is an effective and efficient way to provide patient care experiences for students in the P1-P3 years in accordance with accreditation standards.

Febuxostat and allopurinol are urate-lowering therapies used to treat patients with gout. Following concerns about the cardiovascular safety of febuxostat, the European Medicines Agency recommended a post-licensing study assessing the cardiovascular safety of febuxostat compared with allopurinol. We did a prospective, randomised, open-label, blinded-endpoint, non-inferiority trial of febuxostat versus allopurinol in patients with gout in the UK, Denmark, and Sweden. Eligible patients were 60 years or older, already receiving allopurinol, and had at least one additional cardiovascular risk factor. Those who had myocardial infarction or stroke in the previous 6 months or who had severe congestive heart failure or severe renal impairment were excluded. After a lead-in phase in which allopurinol dose was optimised towards achieving a serum urate concentration of less than 0·357 mmol/L (<6 mg/dL), patients were randomly assigned (1:1, with stratification according to previous cardiovascular events) to continue allopurinol (at the optimised dose) or start febuxostat at 80 mg/day, increasing to 120 mg/day if necessary to achieve the target serum urate concentration. The primary outcome was a composite of hospitalisation for non-fatal myocardial infarction or biomarker-positive acute coronary syndrome; non-fatal stroke; or cardiovascular death. The hazard ratio (HR) for febuxostat versus allopurinol in a Cox proportional hazards model (adjusted for the stratification variable and country) was assessed for non-inferiority (HR limit 1·3) in an on-treatment analysis. This study is registered with the EU Clinical Trials Register (EudraCT 2011-001883-23) and ISRCTN (ISRCTN72443728) and is now closed. From Dec 20, 2011, to Jan 26, 2018, 6128 patients (mean age 71·0 years [SD 6·4], 5225 [85·3%] men, 903 [14·7%] women, 2046 [33·4%] with previous cardiovascular disease) were enrolled and randomly allocated to receive allopurinol (n=3065) or febuxostat (n=3063). By the study end date (Dec 31, 2019), 189 (6·2%) patients in the febuxostat group and 169 (5·5%) in the allopurinol group withdrew from all follow-up. Median follow-up time was 1467 days (IQR 1029–2052) and median on-treatment follow-up was 1324 days (IQR 870–1919). For incidence of the primary endpoint, on-treatment, febuxostat (172 patients [1·72 events per 100 patient-years]) was non-inferior to allopurinol (241 patients [2·05 events per 100 patient-years]; adjusted HR 0·85 [95% CI 0·70–1·03], p<0·0001). In the febuxostat group, 222 (7·2%) of 3063 patients died and 1720 (57·3%) of 3001 in the safety analysis set had at least one serious adverse event (with 23 events in 19 [0·6%] patients related to treatment). In the allopurinol group, 263 (8·6%) of 3065 patients died and 1812 (59·4%) of 3050 had one or more serious adverse events (with five events in five [0·2%] patients related to treatment). Randomised therapy was discontinued in 973 (32·4%) patients in the febuxostat group and 503 (16·5%) patients in the allopurinol group. Febuxostat is non-inferior to allopurinol therapy with respect to the primary cardiovascular endpoint, and its long-term use is not associated with an increased risk of death or serious adverse events compared with allopurinol. Menarini, Ipsen, and Teijin Pharma Ltd.

•Vicarious rewards processing is linked to prosociality and interoception.•Anterior cingulate reward representations can predict prosocial behaviour.•Anterior insula reward representations can predict interoceptive propensity.•More prosocial people are more propense to use interoceptive signals. Every day we constantly observe other people receiving rewards. Theoretical accounts posit that vicarious reward processing might be linked to people's sensitivity to internal body states (interoception) and facilitates a tendency to act prosocially. However, the neural processes underlying the links between vicarious reward processing, interoception, and prosocial behaviour are poorly understood. Previous research has linked vicarious reward processing to the anterior cingulate gyrus (ACCg) and the anterior insula (AI). Can we predict someone's propensity to be prosocial or to be aware of interoceptive signals from variability in how the ACCg and AI process rewards? Here, participants monitored rewards being delivered to themselves or a stranger during functional magnetic resonance imaging. Later, they performed a task measuring their willingness to exert effort to obtain rewards for others, and a task measuring their propensity to be aware and use interoceptive respiratory signals. Using multivariate similarity analysis, we show that people's willingness to be prosocial is predicted by greater similarity between self and other representations in the ACCg. Moreover, greater dissimilarity in self-other representations in the AI is linked to interoceptive propensity. These findings highlight that vicarious reward is linked to bodily signals in AI, and foster prosocial tendencies through the ACCg.

Drought has long been suspected as playing an important role in the abandonment of pre-Columbian Native American settlements across the midcontinental United States between 1350 and 1450 CE. However, high-resolution paleoclimatic reconstructions reflecting local effective moisture (the ratio of precipitation to evaporation) that are located in proximity to Mississippi period (1050–1450 CE) population centers are lacking. Here, we present a 1600-year-long decadally resolved oxygen isotope (δ 18 O) record from Horseshoe Lake (Collinsville, IL), an evaporatively influenced oxbow lake that is centrally located within the largest and mostly densely populated series of Mississippian settlements known as Greater Cahokia. A shift to higher δ 18 O in the Horseshoe Lake sediment record from 1200 to 1400 CE indicates that strongly evaporative conditions (i.e., low effective moisture) were persistent during the leadup to Cahokia’s abandonment. These results support the hypothesis that climate, and drought specifically, strongly impacted agriculturally based pre-Columbian Native American cultures in the midcontinental US and highlights the susceptibility of this region, presently a global food production center, to hydroclimate extremes.

Pain during movement screens is a risk factor for musculoskeletal injury (MSKI). Movement screens often require specialized or clinical expertise and large amounts of time to administer. Evaluate if self-reported pain (1) with movement clearing screens is a risk factor for any MSKI, (2) with movement clearing screens is a risk factor for body region-specific MSKIs, and (3) with a greater number of movement clearing screens progressively increases MSKI risk. Retrospective cohort study. Field-based. Military service members (n = 4222). Active-duty service members self-reported pain during movement clearing screens (Shoulder Clearing, Spinal Extension, Squat-Jump-Land). Musculoskeletal injury data were abstracted up to 180 days post-screening. A traffic light model grouped service members if they self-reported pain during 0 (Green), 1 (Amber), 2 (Red), or 3 (Black) movement clearing screens. Cox proportional hazards models adjusted for age, gender, body mass index, and prior MSKI determined the relationships between pain during movement clearing screens with any and body region-specific MSKIs. Service members self-reporting pain during the Shoulder Clearing (adjusted hazard ratio and 95% confidence interval [HRadj (95% CI)] = 1.58 [1.37, 1.82]), Spinal Extension (HRadj = 1.48 [1.28, 1.87]), or Squat-Jump-Land (HRadj = 2.04 [1.79, 2.32]) tests were more likely to experience any MSKI than service members reporting no pain. Service members with pain during the Shoulder Clearing (HRadj = 3.28 [2.57, 4.19]), Spinal Extension (HRadj = 2.80 [2.26, 3.49]), or Squat-Jump-Land (HRadj = 2.07 [1.76, 2.43]) tests were more likely to experience an upper extremity, spine, back, and torso, or lower extremity MSKI, respectively, than service members reporting no pain. The Amber (HRadj = 1.69 [1.48, 1.93]), Red (HRadj = 2.07 [1.73, 2.48]), and Black (HRadj = 2.31 [1.81, 2.95]) cohorts were more likely to experience an MSKI than the Green cohort. Self-report movement clearing screens in combination with a traffic light model provide clinician- and nonclinician-friendly expedient means to identify service members at MSKI risk.

The junction of bioelectrochemical systems and synthetic biology opens the door to many potentially groundbreaking technologies. When developing these possibilities, choosing the correct chassis organism can save a great deal of engineering effort and, indeed, can mean the difference between success and failure. Choosing the correct chassis for a specific application requires a knowledge of the metabolic potential of the candidate organisms, as well as a clear delineation of the traits, required in the application. In this review, we will explore the metabolic and electrochemical potential of a single genus, Marinobacter. We will cover its strengths, (salt tolerance, biofilm formation and electrochemical potential) and weaknesses (insufficient characterization of many strains and a less developed toolbox for genetic manipulation) in potential synthetic electromicrobiology applications. In doing so, we will provide a roadmap for choosing a chassis organism for bioelectrochemical systems. The junction of bioelectrochemical systems and synthetic biology opens the door to many potentially groundbreaking technologies. When developing these possibilities, choosing the correct chassis organism can save a great deal of engineering effort and, indeed, can mean the difference between success and failure. In this review, we will explore the metabolic and electrochemical potential of the Marinobacter genus, suggesting applications to which these organisms may be best suited.

Background The purpose of this prospective case series study was to compare changes in early postoperative physical activity and physical function between 6 weeks and 3 and 6 months after lumbar spine surgery. Methods Fifty-three patients (mean [95% confidence interval; CI] age = 59.2 [56.2, 62.3] years, 64% female) who underwent spine surgery for a degenerative lumbar condition were assessed at 6 weeks and 3- and 6-months after surgery. The outcomes were objectively-measured physical activity (accelerometry) and patient-reported and objective physical function. Physical activity was assessed using mean steps/day and time spent in moderate to vigorous physical activity (MVPA) over a week. Physical function measures included Oswestry Disability Index (ODI), 12-item Short Form Health Survey (SF-12), Timed Up and Go (TUG), and 10-Meter Walk (10 MW). We compared changes over time in physical activity and function using generalized estimating equations with robust estimator and first-order autoregressive covariance structure. Proportion of patients who engaged in meaningful physical activity (e.g., walked at least 4400 and 6000 steps/day or engaged in at least 150 min/week in MVPA) and achieved clinically meaningful changes in physical function were compared at 3 and 6 months. Results After surgery, 72% of patients initiated physical therapy (mean [95%CI] sessions =8.5 [6.6, 10.4]) between 6 weeks and 3 months. Compared to 6 weeks post-surgery, no change in steps/day or time in MVPA/week was observed at 3 or 6 months. From 21 to 23% and 9 to 11% of participants walked at least 4400 and 6000 steps/day at 3 and 6 months, respectively, while none of the participants spent at least 150 min/week in MVPA at these same time points. Significant improvements were observed on ODI, SF-12, TUG and 10 MW ( p  <  0.05), with over 43 to 68% and 62 to 87% achieving clinically meaningful improvements on these measures at 3 and 6 months, respectively. Conclusion Limited improvement was observed in objectively-measured physical activity from 6 weeks to 6 months after spine surgery, despite moderate to large function gains. Early postoperative physical therapy interventions targeting physical activity may be needed.

Gastroesophageal reflux disease (GERD) is caused by gastric acid entering the esophagus. GERD has high prevalence and is the major risk factor for Barrett’s esophagus (BE) and esophageal adenocarcinoma (EA). We conduct a large GERD GWAS meta-analysis (80,265 cases, 305,011 controls), identifying 25 independent genome-wide significant loci for GERD. Several of the implicated genes are existing or putative drug targets. Loci discovery is greatest with a broad GERD definition (including cases defined by self-report or medication data). Further, 91% of the GERD risk-increasing alleles also increase BE and/or EA risk, greatly expanding gene discovery for these traits. Our results map genes for GERD and related traits and uncover potential new drug targets for these conditions. Gastroesophageal reflux disease (GERD) is a major risk factor for Barret’s esophagus (BE) and esophageal adenocarcinoma (EA). Here, An et al . report 25 genetic loci for GERD, many of which associate with BE and EA or with other traits such as BMI.

ObjectiveGastro-oesophageal reflux disease (GERD) has heterogeneous aetiology primarily attributable to its symptom-based definitions. GERD genome-wide association studies (GWASs) have shown strong genetic overlaps with established risk factors such as obesity and depression. We hypothesised that the shared genetic architecture between GERD and these risk factors can be leveraged to (1) identify new GERD and Barrett’s oesophagus (BE) risk loci and (2) explore potentially heterogeneous pathways leading to GERD and oesophageal complications.DesignWe applied multitrait GWAS models combining GERD (78 707 cases; 288 734 controls) and genetically correlated traits including education attainment, depression and body mass index. We also used multitrait analysis to identify BE risk loci. Top hits were replicated in 23andMe (462 753 GERD cases, 24 099 BE cases, 1 484 025 controls). We additionally dissected the GERD loci into obesity-driven and depression-driven subgroups. These subgroups were investigated to determine how they relate to tissue-specific gene expression and to risk of serious oesophageal disease (BE and/or oesophageal adenocarcinoma, EA).ResultsWe identified 88 loci associated with GERD, with 59 replicating in 23andMe after multiple testing corrections. Our BE analysis identified seven novel loci. Additionally we showed that only the obesity-driven GERD loci (but not the depression-driven loci) were associated with genes enriched in oesophageal tissues and successfully predicted BE/EA.ConclusionOur multitrait model identified many novel risk loci for GERD and BE. We present strong evidence for a genetic underpinning of disease heterogeneity in GERD and show that GERD loci associated with depressive symptoms are not strong predictors of BE/EA relative to obesity-driven GERD loci.