From a baby\'s babbling to a songbird practising a new tune, exploration is critical to motor learning. A hallmark of exploration is the emergence of random walk behaviour along solution manifolds, where successive motor actions are not independent but rather become serially dependent. Such exploratory random walk behaviour is ubiquitous across species\' neural firing, gait patterns and reaching behaviour. The past work has suggested that exploratory random walk behaviour arises from an accumulation of movement variability and a lack of error-based corrections. Here, we test a fundamentally different idea-that reinforcement-based processes regulate random walk behaviour to promote continual motor exploration to maximize success. Across three human reaching experiments, we manipulated the size of both the visually displayed target and an unseen reward zone, as well as the probability of reinforcement feedback. Our empirical and modelling results parsimoniously support the notion that exploratory random walk behaviour emerges by utilizing knowledge of movement variability to update intended reach aim towards recently reinforced motor actions. This mechanism leads to active and continuous exploration of the solution manifold, currently thought by prominent theories to arise passively. The ability to continually explore muscle, joint and task redundant solution manifolds is beneficial while acting in uncertain environments, during motor development or when recovering from a neurological disorder to discover and learn new motor actions.

OBJECTIVE: To analyze the characteristics of overlapping meta-analyses based on randomized controlled trials (RCTs) which reported PD-1/PD-L1 inhibitors in non-small cell cancer (NSCLC).
METHODS: Meta-analyses were identified from English and Chinese databases until January 1, 2022. Differences in characteristics of overlapping meta-analyses that conducted in China and other countries were compared to assess their publication propensity. The corrected covered area (CCA) and coverage of relevant RCTs were analyzed for subtopics according to detailed intervention types. The waste and redundancy of evidence were assessed in the case of PD-1/PD-L1 inhibitor monotherapy for second-line treatment for NSCLC.
RESULTS: Fifty-nine meta-analyses published in English and 17 meta-analyses published in Chinese reporting 26 RCTs were identified. Fifty-three (69.74%) meta-analyses were conducted in China. The overlapping meta-analyses in China were more likely to be from hospitals, supported by government funding, integrate first and second-line therapies. Five of the six subtopics had overlapping meta-analyses according to specific types of interventions. The CCA of overlapping meta-analyses ranged from 33.33 to 63.19%, and the coverage of relevant RCTs ranged from 63.64 to 100%. All the conclusions of overlapping meta-analyses have been consistent in the subtopic of PD-1/PD-L1 inhibitor monotherapy for second-line treatment since 2017.
CONCLUSIONS: Overlapping meta-analyses of PD-1/PD-L1 inhibitors in NSCLC hints that meta-analyses under this topic probably exist serious redundancy. Future research should focus on prospective registration of protocols for systematic reviews/meta-analyses, scientific designed PICO, and cumulative meta-analysis to reduce redundant and wasted studies. Journals should strengthen the requirement for reviewing previously published evidence in manuscript review.

OBJECTIVE: To compare and contrast the diagnostic codes for spinal causes of low back pain (LBP) in 3 disease classification systems (International Classification of Diseases [ICD]-10, International Classification of Primary Care [ICPC]-2 PLUS and Systematized Nomenclature of Medicine Clinical Terms - Australia [SNOMED CT-AU]) and consider how well they are aligned with the diagnostic approach recommended in contemporary clinical practice guidelines for LBP.
METHODS: This was a descriptive study which included 3 disease classification systems: ICD-10, ICPC-2 PLUS and SNOMED CT-AU. Two independent authors extracted relevant LBP codes from each system and mapped the codes to 3 guideline-endorsed categories of spine-related diagnoses for LBP (specific spinal pathology, radicular syndromes, and non-specific LBP) and the various clinical conditions (sub-categories) within each of the 3 categories.
RESULTS: ICD-10, ICPC-2 PLUS, and SNOMED CT-AU had 126, 118 and 100 codes for LBP, respectively. All systems provided codes that would cover the 3 guideline-endorsed categories of spine-related diagnoses for LBP. On the basis of contemporary guidelines, the authors developed lists of discrete sub-categories of specific spinal pathology (56 sub-categories), radicular syndromes (7 sub-categories), and non-specific LBP (10 sub-categories). Each of the classification systems was then mapped against these sub-categories to tally redundancy and determine exhaustiveness. However, no system covered all 73 sub-categories of LBP, and within each system, there was substantial redundancy with up to 22 codes for the same clinical condition.
CONCLUSIONS: LBP diagnostic codes used in popular disease classification systems are out of touch with current approaches to diagnosis, as reflected in contemporary LBP guidelines. Our findings suggest these disease classification systems need revision, but precisely how they should be revised is unclear.

BACKGROUND: Laboratory and radiographic tests are often repeated during inter-hospital transfers from secondary to tertiary emergency departments (ED), despite available data from the sending structure. The aim of this study was to identify the proportion of repeated tests in patients transferred to a tertiary care ED, and to estimate their inappropriateness and their costs.
METHODS: A retrospective chart review of all adult patients transferred from one secondary care ED to a tertiary care ED during the year 2016 was carried out. The primary outcome was the redundancy (proportion of procedure repeated in the 8 h following the transfer, despite the availability of the previous results). Factors predicting the repetition of procedures were identified through a logistic regression analysis. Two authors independently assessed inappropriateness.
RESULTS: In 2016, 432 patients were transferred from the secondary to the tertiary ED, and 251 procedures were repeated: 179 patients (77.2%) had a repeated laboratory test, 34 (14.7%) a repeated radiological procedure and 19 (8.2%) both. Repeated procedures were judged as inappropriate for 197 (99.5%) laboratory tests and for 39 (73.6%) radiological procedures.
CONCLUSIONS: Over half of the patients transferred from another emergency department had a repeated procedure. In most cases, these repeated procedures were considered inappropriate.

BACKGROUND: Acquired Megacolon (AMC) is a condition involving persistent dilatation and lengthening of the colon in the absence of organic disease. Diagnosis depends on subjective radiological, endoscopic or surgical findings in the context of a suggestive clinical presentation. This review sets out to investigate diagnostic criteria of AMC.
METHODS: The literature was searched using the databases - PubMed, Medline via OvidSP, ClinicalKey, Informit and the Cochrane Library. Primary studies, published in English, with more than three patients were critically appraised based on study design, methodology and sample size. Exclusion criteria were studies with the following features: post-operative; megarectum-predominant; paediatric; organic megacolon; non-human; and failure to exclude organic causes.
RESULTS: A review of 23 articles found constipation, abdominal pain, distension and gas distress were predominant symptoms. All ages and both sexes were affected, however, symptoms varied with age. Changes in anorectal manometry, histology and colonic transit are consistently reported. Studies involved varying patient numbers, demographics and data acquisition methods.
CONCLUSIONS: Outcome data investigating the diagnosis of AMC must be interpreted in light of the limitations of the low-level evidence studies published to date. Proposed diagnostic criteria include: (1) the exclusion of organic disease; (2) a radiological sigmoid diameter of ~ 10 cm; (3) and constipation, distension, abdominal pain and/or gas distress. A proportion of patients with AMC may be currently misdiagnosed as having functional gastrointestinal disorders. Our conclusions are inevitably tentative, but will hopefully stimulate further research on this enigmatic condition.

It is widely believed that the brain performs approximate probabilistic inference to estimate causal variables in the world from ambiguous sensory data. To understand these computations, we need to analyze how information is represented and transformed by the actions of nonlinear recurrent neural networks. We propose that these probabilistic computations function by a message-passing algorithm operating at the level of redundant neural populations. To explain this framework, we review its underlying concepts, including graphical models, sufficient statistics, and message-passing, and then describe how these concepts could be implemented by recurrently connected probabilistic population codes. The relevant information flow in these networks will be most interpretable at the population level, particularly for redundant neural codes. We therefore outline a general approach to identify the essential features of a neural message-passing algorithm. Finally, we argue that to reveal the most important aspects of these neural computations, we must study large-scale activity patterns during moderately complex, naturalistic behaviors.

BACKGROUND: Next-generation sequencing (NGS) technologies are arguably the most revolutionary technical development to join the list of tools available to molecular biologists since PCR. For researchers working with nonconventional model organisms one major problem with the currently dominant NGS platform (Illumina) stems from the obligatory fragmentation of nucleic acid material that occurs prior to sequencing during library preparation. This step creates a significant bioinformatic challenge for accurate de novo assembly of novel transcriptome data. This challenge becomes apparent when a variety of modern assembly tools (of which there is no shortage) are applied to the same raw NGS dataset. With the same assembly parameters these tools can generate markedly different assembly outputs.
RESULTS: In this study we present an approach that generates an optimized consensus de novo assembly of eukaryotic coding transcriptomes. This approach does not represent a new assembler, rather it combines the outputs of a variety of established assembly packages, and removes redundancy via a series of clustering steps. We test and validate our approach using Illumina datasets from six phylogenetically diverse eukaryotes (three metazoans, two plants and a yeast) and two simulated datasets derived from metazoan reference genome annotations. All of these datasets were assembled using three currently popular assembly packages (CLC, Trinity and IDBA-tran). In addition, we experimentally demonstrate that transcripts unique to one particular assembly package are likely to be bioinformatic artefacts. For all eight datasets our pipeline generates more concise transcriptomes that in fact possess more unique annotatable protein domains than any of the three individual assemblers we employed. Another measure of assembly completeness (using the purpose built BUSCO databases) also confirmed that our approach yields more information.
CONCLUSIONS: Our approach yields coding transcriptome assemblies that are more likely to be closer to biological reality than any of the three individual assembly packages we investigated. This approach (freely available as a simple perl script) will be of use to researchers working with species for which there is little or no reference data against which the assembly of a transcriptome can be performed.

The number of meta-analyses published annually has increased more than 20-fold between 1994 (n = 386) and 2014 (n = 8203). In examining how much of this increase in meta-analysis publication has genuinely represented novel contributions to clinical medicine and public health, it became clear that there was an abundance of redundant and disorganized meta-analyses, creating confusion and generating considerable debate. Ironically, meta-analyses, which should prevent redundant research, have become a victim of it. Recently, 17 meta-analyses were published based on the results of only 3 randomized controlled trials that studied the role of transcatheter closure of patent foramen ovale for prevention of cryptogenic stroke. In our search of the published literature, we identified at least 10 topics that were the subject of 10 meta-analyses. In the context of overlapping meta-analyses, one questions what needs to be done to put this \"runaway train\" back on track. In this review we examine the practice of redundant meta-analyses and the reasons for its disturbing \"popularity.\" The registration of systematic reviews should be mandatory in prospective registries, such as PROSPERO, and the PRISMA checklist should be updated to incorporate new evidence and mandate the reference of previously published reviews and rationale for any new study.

The etiology and clinical significance of increased radiographic opacity along the dorsal margin of the tracheal lumen has long been debated. Most often, this opacity is attributed to redundancy of the dorsal tracheal membrane (DTM), a condition that occurs with tracheal collapse. We hypothesized that the underlying etiology of this radiographic opacity differs between small breed dogs with tracheal collapse and small or large breed dogs without tracheal collapse. The purpose of this prospective, cross-sectional study was to compare the radiographic appearance of an increased opacity within the trachea to tracheoscopy findings in a group of small and large breed dogs. A total of 17 small breed dogs and 16 large breed dogs were included. Of these, only one did not have a radiographically visible DTM. Small breed dogs were divided into groups with tracheal collapse (n = 8) and those without (n = 9) based on tracheoscopy. Tracheal collapse was absent in larger breed dogs, however both large and small breed dogs demonstrated inward invagination of the DTM. In dogs with tracheal collapse, the DTM occupied a larger percentage of the tracheal luminal height on radiographs and a larger percentage of tracheal circumference on tracheoscopy vs. dogs with an invaginated DTM on tracheoscopy and dogs with no collapse and no invagination of the DTM. Findings supported the hypothesis that increased radiographic opacity along the dorsal margin of the trachea arises from different etiologies in dogs with and without tracheal collapse.

HIGHLIGHTSThe redundant bilateral visual presentation of verbal stimuli decreases asymmetry and increases the cooperation between the two hemispheres.The increased cooperation between the hemispheres is related to semantic information during lexical processing.The inter-hemispheric interaction is represented by both inhibition and cooperation. This study explores inter-hemispheric interaction (IHI) during a lexical decision task by using a behavioral approach, the bilateral presentation of stimuli within a divided visual field experiment. Previous studies have shown that compared to unilateral presentation, the bilateral redundant (BR) presentation decreases the inter-hemispheric asymmetry and facilitates the cooperation between hemispheres. However, it is still poorly understood which type of information facilitates this cooperation. In the present study, verbal stimuli were presented unilaterally (left or right visual hemi-field successively) and bilaterally (left and right visual hemi-field simultaneously). Moreover, during the bilateral presentation of stimuli, we manipulated the relationship between target and distractors in order to specify the type of information which modulates the IHI. Thus, three types of information were manipulated: perceptual, semantic, and decisional, respectively named pre-lexical, lexical and post-lexical processing. Our results revealed left hemisphere (LH) lateralization during the lexical decision task. In terms of inter-hemisphere interaction, the perceptual and decision-making information increased the inter-hemispheric asymmetry, suggesting the inhibition of one hemisphere upon the other. In contrast, semantic information decreased the inter-hemispheric asymmetry, suggesting cooperation between the hemispheres. We discussed our results according to current models of IHI and concluded that cerebral hemispheres interact and communicate according to various excitatory and inhibitory mechanisms, all which depend on specific processes and various levels of word processing.