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Adapting flexibly to changing circumstances is guided by memory of past choices, their outcomes in similar circumstances, and a method for choosing among potential actions. The hippocampus (HPC) is needed to remember episodes, and the prefrontal cortex (PFC) helps guide memory retrieval. Single-unit activity in the HPC and PFC correlates with such cognitive functions. Previous work recorded CA1 and mPFC activity as male rats performed a spatial reversal task in a plus maze that requires both structures, found that PFC activity helps reactivate HPC representations of pending goal choices but did not describe frontotemporal interactions after choices. We describe these interactions after choices here. CA1 activity tracked both current goal location and the past starting location of single trials; PFC activity tracked current goal location better than past start location. CA1 and PFC reciprocally modulated representations of each other both before and after goal choices. After choices, CA1 activity predicted changes in PFC activity in subsequent trials, and the magnitude of this prediction correlated with faster learning. In contrast, PFC start arm activity more strongly modulated CA1 activity after choices correlated with slower learning. Together, the results suggest post-choice HPC activity conveys retrospective signals to the PFC, which combines different paths to common goals into rules. In subsequent trials, prechoice mPFC activity modulates prospective CA1 signals informing goal selection.SIGNIFICANCE STATEMENTHPC and PFC activity supports cognitive flexibility in changing circumstances. HPC signals represent behavioral episodes that link the start, choice, and goal of paths. PFC signals represent rules that guide goal-directed actions. Although prior studies described HPC–PFC interactions preceding decisions in the plus maze, post-decision interactions were not investigated. Here, we show post-choice HPC and PFC activity distinguished the start and goal of paths, and CA1 signaled the past start of each trial more accurately than mPFC. Postchoice CA1 activity modulated subsequent PFC activity, so rewarded actions were more likely to occur. Together, the results show that in changing circumstances, HPC retrospective codes modulate subsequent PFC coding, which in turn modulates HPC prospective codes that predict choices.

In the present study, the micro-mechanical behavior of CoCrFeMnNi high-entropy alloy was investigated using an in-house micro-tensile setup at room temperature and 550 °C at different strain rates. Micro-mechanical properties are compared with those obtained using a commercial macro-tensile setup to check a potential sample size effect. Results show that mechanical properties such as yield strength, ultimate tensile strength and uniform elongation are independent of the sample size. However, the total elongation-to-failure of micro-samples is found to be lower than those of macro-counterparts. Apart from this, the material exhibits serrated plastic flow, which is strain rate dependent in terms of the onset strain and shape of serrations at 550 °C. Furthermore, transmission electron microscopy investigations were performed to correlate the occurrence of serrations to the observed distinct dislocation structures. Microstructural results provide direct evidence that dislocations are curved and hence effectively pinned and unpinned at the lowest applied strain rate, which might be responsible for the occurrence of serrated plastic flow.

To determine the geographic distribution of muscle-invasive bladder cancer mortality according to race in the United States (US). African Americans (AAs) have up to two times the risk of bladder cancer mortality compared to Caucasians. Bladder cancer mortality increases exponentially once it invades the muscle. Geographic heterogeneity in bladder cancer mortality according to race remains to be determined.Analysis of Surveillance, Epidemiology, and End Results (SEER)-Medicare data for 6,044 patients aged 66-85 diagnosed with clinical stage T2-T4 N0M0 bladder cancer from 1 January 2002 to 31 December 2011. Fine and Gray-competing risks regression models were used to assess the association of race with bladder cancer-specific mortality (BCSM) according to tumor registry.Out of 6,044 patients, 5,408 (89.5%) were Caucasian, 352 (5.82%) were non-Hispanic AA, 85 (1.4%) were Hispanic, and 199 (3.29%) were other. Of the 18 registries, AAs with bladder cancer were largely concentrated in Louisiana (19%), New Jersey (17.9%), and Georgia (17.6%). New Jersey was the only registry where AAs had increased risk of BCSM than Caucasians and only for stage T2 disease: (AHR, 1.74; 95% CI 1.22-2.47, p = 0.002). According to treatment, AAs in New Jersey had worse BCSM than Caucasians when they underwent radical cystectomy (AHR, 2.05; 95% CI 1.26-3.35, p = 0.0039) and radiotherapy or chemotherapy alone (AHR, 1.55; 95% CI 1.03-2.35, p = 0.0367).We observed geographic variation in bladder cancer mortality which impacted only one registry with one of the largest population of AAs. These findings support further investigation into the social determinants of race (i.e., socioeconomic status and distance to healthcare facility) and culturally centered healthcare decision making which may drive these results.

BACKGROUND The objective of this study was to describe bladder cancer outcomes as a function of race among patients with high-risk non-muscle-invasive bladder cancer (NMIBC) in an equal-access setting. METHODS A total of 412 patients with high-risk NMIBC who received bacille Calmette-Guerin (BCG) from January 1, 2010, to December 31, 2015, were assessed. The authors used the Kaplan-Meier method to estimate event-free survival and Cox regression to determine the association between race and recurrence, progression, disease-specific, and overall survival outcomes. RESULTS A total of 372 patients who had complete data were included in the analysis; 48 (13%) and 324 (87%) were Black and White, respectively. There was no difference in age, sex, smoking status, or Charlson Comorbidity Index by race. White patients had a higher socioeconomic status with a greater percentage of patients living above the poverty level in comparison with Black patients (median, 85% vs 77%; P < .001). A total of 360 patients (97%) received adequate induction BCG, and 145 patients (39%) received adequate maintenance BCG therapy. There was no significant difference in rates of adequate induction or maintenance BCG therapy according to race. There was no significant difference in recurrence (hazard ratio [HR], 1.53; 95% confidence interval [CI], 0.64-3.63), progression (HR, 0.77; 95% CI, 0.33-1.82), bladder cancer-specific survival (HR, 1.01; 95% CI, 0.30-3.46), or overall survival (HR, 0.97; 95% CI, 0.56-1.66) according to Black race versus White race. CONCLUSIONS In this small study from an equal-access setting, there was no difference in the receipt of BCG or any differences in bladder cancer outcomes according to race.

New findings What is the central question of this study? Does peripheral non-invasive focused ultrasound targeted to the celiac plexus improve inflammatory bowel disease? What is the main finding and its importance? Peripheral non-invasive focused ultrasound targeted to the celiac plexus in a rat model of ulcerative colitis improved stool consistency and reduced stool bloodiness, which coincided with a longer and healthier colon than in animals without focused ultrasound treatment. The findings suggest that this novel neuromodulatory technology could serve as a plausible therapeutic approach for improving symptoms of inflammatory bowel disease. Abstract Individuals suffering from inflammatory bowel disease (IBD) experience significantly diminished quality of life. Here, we aim to stimulate the celiac plexus with non-invasive peripheral focused ultrasound (FUS) to modulate the enteric cholinergic anti-inflammatory pathway. This approach may have clinical utility as an efficacious IBD treatment given the non-invasive and targeted nature of this therapy. We employed the dextran sodium sulfate (DSS) model of colitis, administering lower (5%) and higher (7%) doses to rats in drinking water. FUS on the celiac plexus administered twice a day for 12 consecutive days to rats with severe IBD improved stool consistency scores from 2.2 ± 1 to 1.0 ± 0.0 with peak efficacy on day 5 and maximum reduction in gross bleeding scores from 1.8 ± 0.8 to 0.8 ± 0.8 on day 6. Similar improvements were seen in animals in the low dose DSS group, who received FUS only once daily for 12 days. Moreover, animals in the high dose DSS group receiving FUS twice daily maintained colon length (17.7 ± 2.5 cm), while rats drinking DSS without FUS exhibited marked damage and shortening of the colon (13.8 ± 0.6 cm) as expected. Inflammatory cytokines such as interleukin (IL)-1β, IL-6, IL-17, tumour necrosis factor-α and interferon-γ were reduced with DSS but coincided with control levels after FUS, which is plausibly due to a loss of colon crypts in the former and healthier crypts in the latter. Lastly, overall, these results suggest non-invasive FUS of peripheral ganglion can deliver precision therapy to improve IBD symptomology.

Memory helps us adapt to changing circumstances but needs guidance to retrieve relevant episodes. Episodic memory requires the hippocampus, the prefrontal cortex (PFC) guides memory retrieval, but how their representations interact is unclear. Using state-space analysis of neuronal spiking, we found CA1 and PFC activity within and between rats formed similar, low-dimensional, region-specific “shapes” representing different tasks tested in the same maze. Task shapes were organized by behaviorally salient variables including time and maze start and goal locations. PFC predicted CA1 representations when both regions were needed to solve a spatial memory task, but not in a cue approach task that required neither region. Task demands imposed common dimensions on CA1 and PFC maps whose topologies distinguished episodic and rule-related computations.

Serrated plastic deformation at temperatures close to 0 K has been previously reported in some metals and alloys, and is associated with two possible origins: (i) thermomechanical instability or (ii) mechanical instability. While some recent results indicate that serrations are a mechanical dislocation-based phenomenon, a comprehensive model does not exist. CoCrFeMnNi, an expectedly ideal candidate, exhibits severe serrated plastic deformation with large stress drops in excess of 100 MPa. Furthermore, it also shows cryogenic serrated plastic deformation at a higher temperature (35 K) than previously reported for any other alloy. The exacerbated nature of serrated plastic deformation in CoCrFeMnNi led to the following inferences: (i) temperature and dislocation density are indisputable controlling parameters for cryogenic serrated plastic deformation and they cannot supersede each another; (ii) a phenomenological model is elucidated based on the increasing difficulty for cross-slip with decreasing temperature, leading to sudden massive dislocation proliferation event; (iii) the model establishes a gradual transition from completely non-serrated to completely serrated deformation, mediated by cross-slip, as opposed to the conventional model which proposed a discrete transition; (iv) solute dislocation interaction and associated Stacking Fault Energy (SFE) during deformation plays a key role in controlling dislocation constriction and cross-slip and correspondingly serrated plastic deformation; (v) the need/direct influence of deformation twinning, transformation induced plasticity and especially thermomechanical factors on serrated plastic deformation is invalidated. Some of these points were further clarified through comparisons with CoCrNi and CoNi, also presented in the present article.

Benign prostatic hyperplasia (BPH), a common cause of lower urinary tract symptoms in the elderly male population, has conventionally treated by transurethral resection of the prostate (TURP). During recent years, newer minimally invasive therapies (MITs) have entered the playing field and challenged TURP with their convenience, lack of sexual side effects, and overall safety. The present paper provides an update on the more heavily studied and most recent MITs, analyzing their mechanism of action, tolerability, and efficacy in clinical practice. Particularly, robust clinical data have propelled UroLift and Rezuum to the forefront in the armamentarium of minimally invasive BPH treatment. Newer mechanical therapies such as the temporary implantable nitinol device, ClearRing, ZenFlow Spring, and Butterfly are appealing options as they forego cutting, ablation, heating, or removing prostatic tissue. It is obvious that there is wide variation in the degree of clinical readiness of each modality and only time and long-term, multicenter studies will decide which of these therapies are accepted by the patient and urologist.

Background The role of routine preoperative endoscopy before primary weight loss surgery remains controversial. Objective We reviewed our experience to determine the frequency of abnormal findings in patients undergoing routine preoperative endoscopy before bariatric surgery. Setting A tertiary level, academic-affiliated bariatric surgery practice. Methods A retrospective chart review was performed between July 2014 and June 2016 of patients undergoing routine preoperative endoscopy before primary bariatric surgery. Variables evaluated included preendoscopy symptoms, planned bariatric surgical procedure, abnormal findings on endoscopy, and changes in planned bariatric surgical procedure after endoscopy. Results A total of 631 patients met inclusion criteria. Of patients, 72% (457) were female. The median age was 44 (interquartile range 36–55). The median body mass index was 46 (interquartile range 42–51). Most patients had no preendoscopy clinical symptoms (61.3%). The most frequent abnormal findings included esophagitis (26.5%), hiatal hernia (27.1%), gastric ulcer (4.9%), and biopsy-proven Barrett’s esophagus (4.6%). Although patients with preoperative symptoms were more likely to have abnormal findings on endoscopy, there were no significant differences in rates of Barrett’s esophagus in patients with (5.3%) or without (4.1%) symptoms. Of the total cohort, 18.4% had a change in their planned operation after endoscopy results. Conclusion The findings in our large series suggest selective screening in symptomatic patients only may lead to failure of discovery of foregut pathology that should prompt consideration for changes in the planned bariatric surgical procedure. Further study is necessary to see if our findings have broad applicability.

Microstructural evolution under tribological load is known to change the friction and wear response of the entire tribological system. It is however not yet fully understood, how these changes take place on an elementary, mechanistic level. Revealing the temporal sequence of deformation mechanisms under a tribological load by experiments is scarce. The discrete strain release in the case of deformation twinning allows the identification of their temporal sequence. Therefore, a medium stacking fault energy material, namely CoCrNi, was investigated due to the significant contribution of deformation twinning to the overall deformation at room temperature. The investigated grain showed three activated twin systems. The evolution sequence of these is discussed critically based on several twin intersection mechanisms. The experimental analysis decodes the temporal sequence of the active twinning systems of highest resolved shear stresses for the first time. This approach gives experimental indications for the stress field under a tribological load.

Coarse-grained, metallic materials undergo microstructure refinement during tribological loading. This in turn results in changing tribological properties, so the microstructural evolution is a parameter which should not be underestimated while designing tribological systems. Single-trace experiments were conducted to understand the initiation of deformation mechanisms acting in various tribological systems. The main scope of this work was to investigate the influence of normal and friction forces as well as crystal orientations on the dominating deformation mechanism in a face-centred cubic concentrated solid solution. While varying the normal force is easily realised, varying friction forces were achieved by using several counter body materials paired against CoCrFeMnNi. The subsurface deformation layer was either mediated through dislocation slip or twinning, depending on the grain orientation and on the tribological system. A layer dominated by dislocation-based deformation is characterised by lattice rotation, the formation of a dislocation trace line or subgrain formation. Such behaviour is observed for tribological systems with a low friction coefficient. For systems dominated by deformation twinning, three types of twin appearance were observed: small twins interacting with the surface, large twins and grains with two active twin systems. Two different twinning mechanisms are discussed as responsible for these characteristics. Graphical abstract

Background Upper tract urothelial carcinoma (UTUC) is a heterogeneous disease that presents a clinical management challenge for the urologic surgeon. We assessed treatment patterns, costs, and survival outcomes among patients with nonmetastatic UTUC. Methods We identified 4114 patients diagnosed with nonmetastatic UTUC from 2004 to 2013 in the Survival Epidemiology, and End Results–Medicare population-based database. Patients were stratified into low- or high-risk disease groups. Median total costs from 30 days prior to diagnosis through 365 days after diagnosis were compared between groups. Overall and cancer-specific survival were evaluated using Cox proportional hazards regression. All statistical tests were 2-sided. Results After risk stratification, 1027 (24.9%) and 3087 (75.0%) patients were classified into low- vs high-risk UTUC groups. Most patients underwent at least 1 surgical intervention (95.1%); 68.4% underwent at least 1 endoscopic intervention. Patients diagnosed with high- vs low-risk UTUC were more likely to undergo nephroureterectomy (83.6% vs 72.0%; P Conclusions UTUC continues to be managed primarily with nephroureterectomy, regardless of risk stratification, and patients with high-risk UTUC have worse overall and cancer-specific survival. Substantial costs are associated with management of low- and high-risk UTUC, with the latter being more costly up to 1 year from diagnosis.

We often remember the consequences of past choices to adapt to changing circumstances. Recalling past events requires the hippocampus (HPC), and using stimuli to anticipate outcome values requires the orbitofrontal cortex (OFC).