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Abstract Human cortical maturation has been posited to be organized along the sensorimotor-association axis, a hierarchical axis of brain organization that spans from unimodal sensorimotor cortices to transmodal association cortices. Here, we investigate the hypothesis that the development of functional connectivity during childhood through adolescence conforms to the cortical hierarchy defined by the sensorimotor-association axis. We tested this pre-registered hypothesis in four large-scale, independent datasets (total n = 3355; ages 5–23 years): the Philadelphia Neurodevelopmental Cohort (n = 1207), Nathan Kline Institute-Rockland Sample (n = 397), Human Connectome Project: Development (n = 625), and Healthy Brain Network (n = 1126). Across datasets, the development of functional connectivity systematically varied along the sensorimotor-association axis. Connectivity in sensorimotor regions increased, whereas connectivity in association cortices declined, refining and reinforcing the cortical hierarchy. These consistent and generalizable results establish that the sensorimotor-association axis of cortical organization encodes the dominant pattern of functional connectivity development.

Objectives: To compare the effectiveness of cognitive aid use during resuscitation with no use of cognitive aids on cardiopulmonary resuscitation quality and performance. Methods: This systematic review followed the PICOST format. All randomised controlled trials and non-randomised studies evaluating cognitive aid use during (simulated) resuscitation were included in any setting. Unpublished studies were excluded. We did not include studies that reported cognitive aid use during training for resuscitation alone. Medline, Embase and Cochrane databases were searched from inception until July 2019 (updated August 2022, November 2023, and 23 April 2024). We did not search trial registries. Title and abstract screening, full-text screening, data extraction, risk of bias assessment (using RoB2 and ROBINS-I), and certainty of evidence (using GRADE) were performed by two researchers. PRISMA reporting standards were followed, and registration (PROSPERO CRD42020159162, version 19 July 2022) was performed. No funding has been obtained. Results: The literature search identified 5029 citations. After removing 512 duplicates, reviewing the titles and abstracts of the remaining articles yielded 103 articles for full-text review. Hand-searching identified 3 more studies for full-text review. Of these, 29 studies were included in the final analysis. No clinical studies involving patients were identified. The review was limited to indirect evidence from simulation studies only. The results are presented in five different populations: healthcare professionals managing simulated resuscitations in neonates, children, adult advanced life support, and other emergencies; as well as lay providers managing resuscitations. Main outcomes were adherence to protocol or process, adherence to protocol or process assessed by performance score, CPR performance and retention, and feasibility of chatbot guidance. The risk of bias assessment ranged from low to high. Studies in neonatal, paediatric and adult life support delivered by healthcare professionals showed benefits of using cognitive aids, however, some studies evaluating resuscitations by lay providers reported undesirable effects. The performance of a meta-analysis was not possible due to significant methodological heterogeneity. The certainty of evidence was rated as moderate to very low due to serious indirectness, (very) serious risk of bias, serious inconsistency and (very) serious imprecision. Conclusion: Because of the very low certainty evidence from simulation studies, we suggest that cognitive aids should be used by healthcare professionals during resuscitation. In contrast, we do not suggest use of cognitive aids for lay providers, based on low certainty evidence.

Aim: To systematically review published literature to evaluate the impact of gamified learning on educational and clinical outcomes during life support education. Methods: This systematic review was conducted as part of the continuous evidence evaluation process of the International Liaison Committee on Resuscitation (ILCOR). A search of PubMed, Embase, and Cochrane was conducted from inception until February 12, 2024. Studies examining incorporation of gamified learning were eligible for inclusion. Reviewers independently extracted data on study design and outcomes; appropriate risk of bias assessment tools were used across all outcomes. Results: 2261 articles were identified and screened, yielding sixteen articles (seven randomized trials, nine observational studies) which comprised the final review. No meta-analyses were conducted due to significant heterogeneity of intervention, population, and outcome. Only one study was found to have a low risk of bias; the remaining studies were found to have moderate to high risk. Fourteen studies were in healthcare providers and two were in laypersons. Most studies (11 of 16) examined the impact of a digital platform (computer or smartphone). Most (15 of 16) studies found a positive effect on at least one educational domain; one study found no effect. No included study found a negative effect on any educational domain. Conclusion: This systematic review found a very heterogeneous group of studies with low certainty evidence, all but one of which demonstrated a positive effect on one or more educational domains. Future studies should examine the underlying causes of improved learning with gamification and assess the resource requirements with implementation and dissemination of gamified learning.

Aim: To evaluate the effectiveness of Rapid Cycle Deliberate Practice (RCDP) compared to traditional instruction or other forms of learning on resuscitation training outcomes and on clinical and/or patient-related outcomes. Methods: As part of the continuous evidence evaluation process of the International Liaison Committee on Resuscitation it was conducted this review and searched Medline, Embase and Cochrane from inception to Feb 12th, 2024. Risk of bias assessment was performed with the Risk of Bias in Non-randomized Studies of Interventions assessment tool and the Revised Cochrane risk-of-bias tool for randomized trials. The GRADE approach was used to evaluate the overall certainty of evidence for each outcome. Results: 4420 abstracts were retrieved by the initial search and 10 additional studies were identified through other resources. Sixty-five studies were selected for eligibility and nine simulated studies met the inclusion criteria. A meta-analysis was performed on three outcomes: time to chest compressions, time to defibrillation and time to first epinephrine given, which showed that RCDP had significantly shorter time to defibrillation and time to administration of epinephrine than controls. The overall certainty of evidence was very low across all outcomes due to risk of bias, inconsistency, indirectness, and imprecision. Conclusion: It may be reasonable to include RCDP as an instructional design feature of basic and advanced life support training. However, substantial variations of delivering RCDP exist and there is no uniform use of RCDP. Further research is necessary on medium/long-term effects of RCDP training, and on the effects on different target groups of training.

As essential components of gene expression networks, transcription factors regulate neural circuit assembly. The homeobox transcription factor encoding gene, gs homeobox 1 (gsx1), is expressed in the developing visual system; however, no studies have examined its role in visual system formation. In zebrafish, retinal ganglion cell (RGC) axons that transmit visual information to the brain terminate in ten arborization fields (AFs) in the optic tectum (TeO), pretectum (Pr), and thalamus. Pretectal AFs (AF1-AF9) mediate distinct visual behaviors, yet we understand less about their development compared to AF10 in the TeO. Using gsx1 zebrafish mutants, immunohistochemistry, and transgenic lines, we observed that gsx1 is required for vesicular glutamate transporter, Tg(slc17a6b:DsRed), expression in the Pr, but not overall neuron number. gsx1 mutants have normal eye morphology, yet they exhibit impaired visual ability during prey capture. RGC axon volume in the gsx1 mutant Pr and TeO is reduced, and AF7 that is active during feeding is missing which is consistent with reduced hunting performance. Timed laser ablation of Tg(slc17a6b:DsRed)-positive cells reveals that they are necessary for AF7 formation. This work is the first to implicate gsx1 in establishing cell identity and functional neural circuits in the visual system.

Abstract Stem cell transplantation (SCT) has been an integral treatment modality for multiple myeloma (MM) for decades. However, as standard‐of‐care therapies have improved, the benefit of SCT has been repeatedly called into question. This retrospective study evaluated the association between SCT in the first line of therapy (LOT) and outcomes for patients with newly diagnosed multiple myeloma (NDMM) in the United States. We included patients from a de‐identified electronic health record‐derived database who initiated front‐line MM therapy between January 1, 2016, and January 31, 2022. Overall, 18.8% (1127 of 5996 patients) received SCT in the first LOT. Multivariable‐adjusted Cox proportional hazards models, in which SCT was modeled as time varying, revealed longer real‐world progression‐free survival (rwPFS; hazard ratio [HR] 0.49; 95% confidence interval [CI] 0.43–0.57) and real‐world overall survival (rwOS; HR 0.47; 95% CI 0.39–0.56) for patients who received SCT in the first LOT. The degree of rwPFS and rwOS benefit imparted by SCT was consistent across all subgroups examined, including patients aged ≥75 years, women, non‐Hispanic Black/African American patients, those with renal impairment, and those with high‐risk cytogenetics. Findings from this analysis of real‐world patients with NDMM suggest that SCT remains an important standard of care in the era of novel therapies.

BackgroundUsing virtual patients, facilitated by natural language processing, provides a valuable educational experience for learners. Generating a large, varied sample of realistic and appropriate responses for virtual patients is challenging. Artificial intelligence (AI) programs can be a viable source for these responses, but their utility for this purpose has not been explored. ObjectiveIn this study, we explored the effectiveness of generative AI (ChatGPT) in developing realistic virtual standardized patient dialogues to teach prenatal counseling skills. MethodsChatGPT was prompted to generate a list of common areas of concern and questions that families expecting preterm delivery at 24 weeks gestation might ask during prenatal counseling. ChatGPT was then prompted to generate 2 role-plays with dialogues between a parent expecting a potential preterm delivery at 24 weeks and their counseling physician using each of the example questions. The prompt was repeated for 2 unique role-plays: one parent was characterized as anxious and the other as having low trust in the medical system. Role-play scripts were exported verbatim and independently reviewed by 2 neonatologists with experience in prenatal counseling, using a scale of 1-5 on realism, appropriateness, and utility for virtual standardized patient responses. ResultsChatGPT generated 7 areas of concern, with 35 example questions used to generate role-plays. The 35 role-play transcripts generated 176 unique parent responses (median 5, IQR 4-6, per role-play) with 268 unique sentences. Expert review identified 117 (65%) of the 176 responses as indicating an emotion, either directly or indirectly. Approximately half (98/176, 56%) of the responses had 2 or more sentences, and half (88/176, 50%) included at least 1 question. More than half (104/176, 58%) of the responses from role-played parent characters described a feeling, such as being scared, worried, or concerned. The role-plays of parents with low trust in the medical system generated many unique sentences (n=50). Most of the sentences in the responses were found to be reasonably realistic (214/268, 80%), appropriate for variable prenatal counseling conversation paths (233/268, 87%), and usable without more than a minimal modification in a virtual patient program (169/268, 63%). ConclusionsGenerative AI programs, such as ChatGPT, may provide a viable source of training materials to expand virtual patient programs, with careful attention to the concerns and questions of patients and families. Given the potential for unrealistic or inappropriate statements and questions, an expert should review AI chat outputs before deploying them in an educational program.

Examination of the impact of race and ethnicity on multiple myeloma (MM) outcomes has yielded inconsistent results. This retrospective, real-world (RW) study describes patient, disease, and treatment characteristics (and associations with survival outcomes) among newly diagnosed MM patients of non-Hispanic (NH) Black/African American (AA) and NH White race/ethnicity in the US. We included patients from the nationwide Flatiron Health electronic health record-derived de-identified database who initiated first line of therapy (LOT) for MM between January 1, 2016 and March 31, 2022. Of 4,614 patients in our study cohort, 23.3% were NH Black/AA. Non-Hispanic Black/AA patients were younger than NH White patients at diagnosis (median 68 vs. 71 years) and more likely to be female (53.4% vs. 43.5%). Rates of high-risk cytogenetics and 1q21+ were similar between races/ethnicities. The most common primary regimen used was lenalidomide-bortezomib-dexamethasone (50.1% of NH Black/AA and 48.1% of NH White patients). Receipt of stem cell transplantation during first LOT was less common among NH Black/AA (16.5%) than NH White (21.9%) patients. Unadjusted RW progression-free survival (rwPFS) and overall survival (rwOS) were similar between races/ethnicities. After multivariable adjustment, NH Black/AA race/ethnicity was associated with slightly inferior rwPFS (hazard ratio [HR]=1.13; 95% confidence interval [CI]: 1.01-1.27). The difference in rwOS (HR=1.12; 95% CI: 0.98-1.28) was not statistically significant. In general, associations between risk factors for rwPFS and rwOS were consistent between races/ethnicities. Findings from this analysis help to inform clinicians about the impact of race/ethnicity on MM treatment paradigms and outcomes in the US.

Specimens of 316 L stainless steel were printed using laser powder bed fusion (LPBF), a popular metal additive manufacturing (AM) technique, with varying island sizes. Not many researchers have considered the impact of spatter while optimizing LPBF printing parameters. In this research, the influence of spatter was considered while also investigating the effect of varied island size on the microstructure, surface roughness, microhardness, and corrosion resistance of LPBF-316 L. No correlation was observed between surface roughness or microhardness and minor variations in island size. However, a correlation was drawn between varied island sizes and porosity in LPBF-316 L. The specimens associated with larger island sizes showed significantly enhanced corrosion resistance due to fewer manufacturing defects and reduced porosity, attributed to the minimal influence of the spatter. Based on analysis, the LPBF parameters were revised, which lead to superior corrosion resistance of LPBF-316 L, attributed to high density and reduced porosity.

Leucine-rich repeat kinase 2 (LRRK2) is a serine–threonine protein kinase belonging to the ROCO protein family. Within the kinase domain of LRRK2, a point mutation known as LRRK2 G2019S has emerged as the most prevalent variant associated with Parkinson’s disease. Recent clinical studies have indicated that G2019S carriers have an elevated risk of cancers, including colon cancer. Despite this observation, the underlying mechanisms linking LRRK2 G2019S to colon cancer remain elusive. In this study, employing a colitis-associated cancer (CAC) model and LRRK2 G2019S knock-in (KI) mouse model, we demonstrate that LRRK2 G2019S promotes the pathogenesis of colon cancer, characterized by increased tumor number and size in KI mice. Furthermore, LRRK2 G2019S enhances intestinal epithelial cell proliferation and inflammation within the tumor microenvironment. Mechanistically, KI mice exhibit heightened susceptibility to DSS-induced colitis, with inhibition of LRRK2 kinase activity ameliorating colitis severity and CAC progression. Our investigation also reveals that LRRK2 G2019S promotes inflammasome activation and exacerbates gut epithelium necrosis in the colitis model. Notably, GSDMD inhibitors attenuate colitis in LRRK2 G2019S KI mice. Taken together, our findings offer experimental evidence indicating that the gain-of-kinase activity in LRRK2 promotes colorectal tumorigenesis, suggesting LRRK2 as a potential therapeutic target in colon cancer patients exhibiting hyper LRRK2 kinase activity.

Abstract Background Post-traumatic stress disorder (PTSD) is a debilitating disorder defined by the onset of intrusive, avoidant, negative cognitive or affective, and/or hyperarousal symptoms after witnessing or experiencing a traumatic event. Previous voxel-based morphometry studies have provided insight into structural brain alterations associated with PTSD with notable heterogeneity across these studies. Furthermore, how structural alterations may be associated with brain function, as measured by task-free and task-based functional connectivity, remains to be elucidated. Methods Using emergent meta-analytic techniques, we sought to first identify a consensus of structural alterations in PTSD using the anatomical likelihood estimation (ALE) approach. Next, we generated functional profiles of identified convergent structural regions utilizing resting-state functional connectivity (rsFC) and meta-analytic co-activation modeling (MACM) methods. Finally, we performed functional decoding to examine mental functions associated with our ALE, rsFC, and MACM brain characterizations. Results We observed convergent structural alterations in a single region located in the medial prefrontal cortex. The resultant rsFC and MACM maps identified functional connectivity across a widespread, whole-brain network that included frontoparietal and limbic regions. Functional decoding revealed overlapping associations with attention, memory, and emotion processes. Conclusions Consensus-based functional connectivity was observed in regions of the default mode, salience, and central executive networks, which play a role in the tripartite model of psychopathology. Taken together, these findings have important implications for understanding the neurobiological mechanisms associated with PTSD.

Abstract The Brain Imaging Data Structure (BIDS) established community consensus on the organization of data and metadata for several neuroimaging modalities. Traditionally, BIDS had a strong focus on functional magnetic resonance imaging (MRI) datasets and lacked guidance on how to store multimodal structural MRI datasets. Here, we present and describe the BIDS Extension Proposal 001 (BEP001), which adds a range of quantitative MRI (qMRI) applications to the BIDS. In general, the aim of qMRI is to characterize brain microstructure by quantifying the physical MR parameters of the tissue via computational, biophysical models. By proposing this new standard, we envision standardization of qMRI through multicenter dissemination of interoperable datasets. This way, BIDS can act as a catalyst of convergence between qMRI methods development and application-driven neuroimaging studies that can help develop quantitative biomarkers for neural tissue characterization. In conclusion, this BIDS extension offers a common ground for developers to exchange novel imaging data and tools, reducing the entrance barrier for qMRI in the field of neuroimaging.

Abstract Background To compare validity evidence for dichotomous and trichotomous versions of a neonatal intubation (NI) procedural skills checklist. Methods NI skills checklists were developed utilizing an existing framework. Experts were trained on scoring using dichotomous and trichotomous checklists, and rated recordings of 23 providers performing simulated NI. Videolaryngoscope recordings of glottic exposure were evaluated using Cormack-Lehane (CL) and Percent of Glottic Opening scales. Internal consistency and reliability of both checklists were analyzed, and correlations between checklist scores, airway visualization, entrustable professional activities (EPA), and global skills assessment (GSA) were calculated. Results During rater training, raters gave significantly higher scores on better provider performance in standardized videos (both p

Abstract Rezafungin is a novel echinocandin being developed for the treatment and prevention of invasive fungal infections. The objectives of this randomized, double‐blind study in healthy adults were to determine the safety, tolerability, and pharmacokinetics of rezafungin after subcutaneous (s.c.) administration. The study design consisted of six sequential cohorts of eight subjects, except for the first cohort with four subjects. The subjects were randomized in a 3:1 ratio of rezafungin to placebo and were to receive a single dose of 1, 10, 30, 60, 100, or 200 mg. The most common adverse events (AEs) were increased alanine aminotransferase and sinus bradycardia (unsolicited) and erythema at the injection site (solicited). Unsolicited AEs were generally mild to moderate and not rezafungin‐related. Although the study was terminated after the 10 mg dose cohort due to concerns of potential increased severity of injection site reactions, no predetermined dose escalation halting criteria were met. Following the 10 mg single s.c. dose of rezafungin (n = 6), the geometric mean (GM) maximum concentration (Cmax) was 105.0 ng/ml and the median time to Cmax was 144 h. The GM area under the concentration‐time curve was 32,770 ng*h/ml. The median estimated terminal half‐life was 193 h. The GM apparent oral clearance was 0.255 L/h and the GM apparent volume of distribution was 68.5 L. This study demonstrates that a single s.c. dose of rezafungin in healthy adult subjects: (1) did not result in serious AEs, death, or withdrawal from the study due to an AE; and (2) produced a pharmacokinetic profile with long exposure period postadministration. In an effort to reduce the occurrence of injection site reactions, a re‐evaluation of the rezafungin s.c. formulation could be considered in the future.

ABSTRACT Rezafungin is a novel once-weekly echinocandin for intravenous injection currently in development for the treatment of Candida infections and the prevention of Candida, Aspergillus, and Pneumocystis infections in allogeneic blood and marrow transplant recipients. While in vitro data indicated that rezafungin exposure was unlikely to be affected by commonly prescribed medicines, interactions resulting in the altered systemic exposure of some drugs coadministered with rezafungin could not be excluded. Two phase 1 open label crossover studies, conducted in healthy subjects, examined drug interactions between rezafungin and multiple drug probe cytochrome P450 (CYP) substrates and/or transporter proteins, immunosuppressants, and cancer therapies. Statistical analysis compared the outcomes for drugs coadministered with rezafungin to those for the drugs administered alone. The geometric mean ratio was reported, and a default 90% confidence interval (CI) no-effect equivalence range of 80 to 125% was used for the maximal plasma concentration (Cmax), the area under the curve from time zero to the final sampling time point (AUC0–t), and the AUC from time zero to infinity (AUC0–∞). Most probes and concomitant drugs were within the equivalence range. For tacrolimus, ibrutinib, mycophenolic acid, and venetoclax, the AUC or Cmax was reduced (10 to 19%), with lower bounds of the 90% CI values falling outside the no-effect range. The rosuvastatin AUC and Cmax and the repaglinide AUC0–∞ were increased (12 to 16%), with the 90% CI being marginally above the upper bound. Overall, the in vitro and in vivo data demonstrated a low drug interaction potential with rezafungin via CYP substrate/transporter pathways and commonly prescribed comedications, suggesting that coadministration was unlikely to result in clinically significant effects. Treatment-emergent adverse events were typically mild, and rezafungin was generally well tolerated. IMPORTANCE Antifungal agents used to treat life-threatening infections are often associated with severe drug-drug interactions (DDIs) that may limit their usefulness. Rezafungin, a newly approved once-weekly echinocandin, has been shown to be free of DDIs based on extensive nonclinical and clinical testing described in this study.

Our goal was to validate the use of dermal swabs to evaluate both reproductive and stress physiology in the California two-spot octopus, Octopus bimaculoides. Our objectives were to (1) use dermal swabs to evaluate glucocorticoids and reproductive hormones of O. bimaculoides; (2) determine the influence of life stage on hormone production (glucocorticoids in all individuals; testosterone, estrogen, and progesterone in females; and testosterone in males) of reproductive (n = 4) and senescent (n = 8) individuals to determine the effect of age on hormonal patterns; and (3) determine whether these hormones change significantly in response to an acute stressor. For the stress test, individuals were first swabbed for a baseline and then chased around the aquarium with a net for 5 min. Afterward, individuals were swabbed for 2 h at 15 min intervals to compare to the pre-stress test swab. Reproductive individuals responded to the stressor with a 2-fold increase in dermal cortisol concentrations at 15 and 90 min. Six of the eight senescent individuals did not produce a 2-fold increase in dermal cortisol concentrations. Reproductive individuals had significantly higher sex hormone concentrations compared to senescent individuals (progesterone and estradiol measured in females, and testosterone for both sexes). After the stressor, only reproductive males produced a 2-fold increase in dermal testosterone concentrations, while sex hormones in females showed no change. The stress hormone cortisol was significantly higher in senescent than in reproductive individuals, independent of sex. Dermal corticosterone concentrations were highest in senescent females followed by senescent males, and lowest in reproductive individuals regardless of sex. Dermal swabs provide an effective and noninvasive means for evaluating octopus hormones. Application of these indicators may be imperative as cephalopods are more commonly cultured in captivity for experimentation, display, and consumption.

Introduction: Positive pressure ventilation (PPV) is a critical skill for neonatal resuscitation. We hypothesized that telecoaching would improve PPV performance in neonatal providers during simulated neonatal resuscitations. Setting: Level IV neonatal intensive care unit (NICU). Methods: This prospective crossover study included 14 experienced NICU nurses and respiratory therapists who performed PPV on a mannequin that recorded parameters of ventilation efficiency. Participants were randomized to practice independently (control) or with live feedback from a remote facilitator through audiovisual connection (intervention) and then switched to the opposite group. Participants' mask leak percentage, ventilation rates, and pressure delivery were analyzed. Results: The primary outcome of mask leak percentage was significantly increased in the telecoaching group (19% [interquartile range {IQR} 14?59.25] vs. 100% [IQR 88?100] leak, p?=?0.0001). The secondary outcome of peak inspiratory pressure (PIP) delivery was also increased (median 27.6 [IQR 23.5?34.7] vs. 23.3 [IQR 19.1?32.8] cmH2O, p?0.001). Differences in ventilation rates were not statistically significant (55 vs. 58 breaths/min, p?=?0.51). Conclusion: Participants demonstrated better PPV performance during telecoaching with less mask leak. The intervention group also had higher measured peak inspiratory pressures. Telecoaching may be a feasible method to provide real-time feedback to health care providers during simulated neonatal resuscitations. Hypothesis: Neonatal providers who receive telecoaching during simulated resuscitations will perform PPV more effectively than those who do not receive telecoaching.

The Brain Imaging Data Structure (BIDS) is a standard for organizing and describing neuroimaging datasets, serving not only to facilitate the process of data sharing and aggregation, but also to simplify the application and development of new methods and software for working with neuroimaging data. Here, we present an extension of BIDS to include positron emission tomography (PET) data, also known as PET-BIDS, and share several open-access datasets curated following PET-BIDS along with tools for conversion, validation and analysis of PET-BIDS datasets.

The Brain Imaging Data Structure (BIDS) is a specification for organizing, sharing, and archiving neuroimaging data and metadata in a reusable way. First developed for magnetic resonance imaging (MRI) datasets, the community-led specification evolved rapidly to include other modalities such as magnetoencephalography, positron emission tomography, and quantitative MRI (qMRI). In this work, we present an extension to BIDS for microscopy imaging data, along with example datasets. Microscopy-BIDS supports common imaging methods, including 2D/3D, ex/in vivo, micro-CT, and optical and electron microscopy. Microscopy-BIDS also includes comprehensible metadata definitions for hardware, image acquisition, and sample properties. This extension will facilitate future harmonization efforts in the context of multi-modal, multi-scale imaging such as the characterization of tissue microstructure with qMRI.

Cephalopods have the potential to become useful experimental models in various fields of science, particularly in neuroscience, physiology, and behavior. Their complex nervous systems, intricate color- and texture-changing body patterns, and problem-solving abilities have attracted the attention of the biological research community, while the high growth rates and short life cycles of some species render them suitable for laboratory culture. Octopus chierchiae is a small octopus native to the central Pacific coast of North America whose predictable reproduction, short time to maturity, small adult size, and ability to lay multiple egg clutches (iteroparity) make this species ideally suited to laboratory culture. Here we describe novel methods for multigenerational culture of O. chierchiae, with emphasis on enclosure designs, feeding regimes, and breeding management. O. chierchiae bred in the laboratory grow from a 3.5 mm mantle length at hatching to an adult mantle length of approximately 20–30 mm in 250–300 days, with 15 and 14% survivorship to over 400 days of age in first and second generations, respectively. O. chierchiae sexually matures at around 6 months of age and, unlike most octopus species, can lay multiple clutches of large, direct-developing eggs every ∼30–90 days. Based on these results, we propose that O. chierchiae possesses both the practical and biological features needed for a model octopus that can be cultured repeatedly to address a wide range of biological questions.

Objective This study compares two methods for clinical diagnosis of childhood pneumonia that aim to estimate rates of underdiagnosis and overdiagnosis of childhood pneumonia by examining the sensitivity of Integrated Management of Childhood Diseases implementation in routine care against lung ultrasound (LUS) diagnosis.Setting We conducted observations in 83 public health facilities (dispensaries, health centres and district hospitals) in Pwani, Dodoma and Tabora, Tanzania between October and December 2017.Methods We used a novel method to estimate rates of underdiagnosis and overdiagnosis of childhood pneumonia by comparing directly observed public provider diagnoses to the results of diagnoses made by trained clinicians using Mindray DP-10 ultrasound machines. We perform multivariate analysis to identify confounding effects and robustness checks to bound the result. We also explore a number of observable characteristics correlated with higher rates of agreement between provider diagnoses and ultrasound diagnoses.Results We observed 93 providers conducting exams on patients aged 2 months–5 years who presented respiratory symptoms or were given a respiratory diagnosis by the provider. Of these 957 patients, 110 were excluded from analysis resulting in a final sample of 847.17.6% of cases identified as pneumonia via LUS examinations in our sample were diagnosed as pneumonia by providers, suggesting that a significant number of pneumonia cases for which care is sought in the public sector go undiagnosed. Provider knowledge of breath counting and years of experience are positively correlated with higher agreement. While clinical examination rates are not statistically correlated with agreement, it is notable that providers conducted a clinical examination on only about one-third of patients in the sample.Conclusion Our results suggest that provider training and knowledge of clinical examination protocols for pneumonia diagnosis are predictive of correct diagnosis of pneumonia and should be further explored in future research as a tool for improving quality of care.

Background: High-level disinfection protects tens-of-millions of patients from the transmission of viruses on reusable medical devices. The efficacy of high-level disinfectants for preventing human papillomavirus (HPV) transmission has been called into question by recent publications, which if true, would have significant public health implications. Methods: Evaluation of the clinical relevance of these published findings required the development of novel methods to quantify and compare: (i) Infectious titres of lab-produced, clinically-sourced, and animal-derived papillomaviruses, (ii) The papillomavirus dose responses in the newly developed in vitro and in vivo models, and the kinetics of in vivo disease formation, and (iii) The efficacy of high-level disinfectants in inactivating papillomaviruses in these systems. Findings: Clinical virus titres obtained from cervical lesions were comparable to those obtained from tissue (raft-culture) and in vivo models. A mouse tail infection model showed a clear dose-response for disease formation, that papillomaviruses remain stable and infective on fomite surfaces for at least 8 weeks without squames and up to a year with squames, and that there is a 10-fold drop in virus titre with transfer from a fomite surface to a new infection site. Disinfectants such as ortho-phthalaldehyde and hydrogen peroxide, but not ethanol, were highly effective at inactivating multiple HPV types in vitro and in vivo. Interpretation: Together with comparable results presented in a companion manuscript from an independent laboratory, this work demonstrates that high-level disinfectants inactivate HPV and highlights the need for standardized and well-controlled methods to assess HPV transmission and disinfection. Funding: Advanced Sterilization Products, UK-MRC (MR/S024409/1 and MC-PC-13050) and Addenbrookes Charitable Trust

Objective: To compare quantified terminal ileal (TI) motility during MR enterography (MRE) with histopathological severity of acute inflammation in Crohn's disease.Methods: A total of 28 Crohn's patients underwent MRE and endoscopic TI biopsy. Axial and coronal TrueFISP, HASTE and post-gadolinium VIBE images were supplemented by multiple coronal TrueFISP cine motility sequences through the small bowel volume. TI motility index (MI) was quantified using validated software; an acute inflammation score (eAIS; 0-6) was assigned to the biopsy. Two observers qualitatively scored mural thickness, T2 signal, contrast enhancement and perimural oedema (0-3) to produce an activity score (aMRIs) based on anatomical MRI. The association among the MI, eAIS and aMRIs was tested using Spearman's rank correlation. Wilcoxon rank sum test compared motility in subjects with and without histopathological inflammation.Results: Mean MI and mean eAIS were 0.27 (range 0.06-0.55) and 1.5 (range 0-5), respectively. There was a significant difference in MI between non-inflamed (mean 0.37, range 0.13-0.55) and inflamed (mean 0.19, range 0.06-0.44) TI, P = 0.002, and a significant negative correlation between MI and both eAIS (Rho = -0.52, P = 0.005) and aMRIs (R = -0.7, P < 0.001).Conclusion: Quantified TI motility negatively correlates with histopathological measures of disease activity and existing anatomical MRI activity biomarkers.Key Points: • Magnetic resonance imaging is increasingly used to assess Crohn's disease. • MRI measurements can provide a quantitative assessment of small bowel motility. • MR enterography can grade Crohn's disease. • Small bowel motility can be used as a marker of inflammatory activity. [ABSTRACT FROM AUTHOR]

Objective: To determine how commercial software platform upgrades impact on derived parameters for colorectal cancer.Materials and Methods: Following ethical approval, 30 patients with suspected colorectal cancer underwent Perfusion CT using integrated 64 detector PET/CT before surgery. Analysis was performed using software based on modified distributed parameter analysis (Perfusion software version 4; Perfusion 4.0), then repeated using the previous version (Perfusion software version 3; Perfusion 3.0). Tumour blood flow (BF), blood volume (BV), mean transit time (MTT) and permeability surface area product (PS) were determined for identical regions-of-interest. Slice-by-slice and 'whole tumour' variance was assessed by Bland-Altman analysis.Results: Mean BF, BV and PS was 20.4%, 59.5%, and 106% higher, and MTT 14.3% shorter for Perfusion 4.0 than Perfusion 3.0. The mean difference (95% limits of agreement) were +13.5 (-44.9 to 72.0), +2.61 (-0.06 to 5.28), -1.23 (-6.83 to 4.36), and +14.2 (-4.43 to 32.8) for BF, BV, MTT and PS respectively. Within subject coefficient of variation was 36.6%, 38.0%, 27.4% and 60.6% for BF, BV, MTT and PS respectively indicating moderate to poor agreement.Conclusion: Software version upgrades of the same software platform may result in significantly different parameter values, requiring adjustments for cross-version comparison. [ABSTRACT FROM AUTHOR]

Objective: To derive an MRI score for assessing severity, therapeutic response and prognosis in acute severe inflammatory colitis.Methods: Twenty-one patients with acute severe colitis underwent colonic MRI after admission and again (n = 16) after median 5 days of treatment. Using T2-weighted images, two radiologists in consensus graded segmental haustral loss, mesenteric and mural oedema, mural thickness, and small bowel and colonic dilatation producing a total colonic inflammatory score (TCIS, range 6-95). Pre- and post-treatment TCIS were compared, and correlated with CRP, stool frequency, and number of inpatient days (therapeutic response marker). Questionnaire assessment of patient worry, satisfaction and discomfort graded 1 (bad) to 7 (good) was administeredResults: Admission TCIS correlated significantly with CRP (Kendall's tau=0.45, 95% confidence interval [CI] 0.11-0.79, p = 0.006), and stool frequency (Kendall's tau 0.39, 95% CI 0.14-0.64, p = 0.02). TCIS fell after treatment (median [22 range 15-31]) to median 20 [range 8-25], p = 0.01. Admission TCIS but not CRP or stool frequency was correlated with length of inpatient stay (Kendall's tau 0.40, 95% CI 0.11-0.69, p = 0.02). Patients reported some discomfort (median score 4) during MRI.Conclusions: MRI TCIS falls after therapy, correlates with existing markers of disease severity, and in comparison may better predict therapeutic response. [ABSTRACT FROM AUTHOR]

Patient-controlled analgesia (PCA) therapy has become an accepted intervention for delivering pain management in a wide variety of patient populations. The principle of patient-controlled analgesia is to provide patient control over medication delivery. Unfortunately, PCA has come under great scrutiny since its introduction almost 40 years ago. This article focuses on the benefits and safety concerns of PCA and focuses on points that prescribers and nurses should keep in mind. [ABSTRACT FROM AUTHOR]

This study aims to determine inter- and intra-observer variation in MRI measurements of relative bowel wall signal intensity (SI) in Crohn's disease. Twenty-one small bowel MRI examinations (11 male, mean age 40), including T1-weighted acquisitions acquired 30 to 120s post-gadolinium, were analysed. Maximal bowel wall SI (most avid, conspicuous contrast enhancement) in designated diseased segments was measured by two radiologists and two trainees using self-positioned "free" regions of interest (ROIs) followed by "fixed" ROIs chosen by one radiologist, and this procedure was repeated 1 month later. Relative enhancement (post-contrast SI minus pre-contrast SI/pre-contrast SI) was calculated. Data were analysed using Bland-Altman limits of agreement and intra-class correlation. Inter-observer agreement for relative enhancement was poor (spanning over 120%) using a free ROI-95% limits of agreement -0.69, 0.70 and -0.47, 0.74 for radiologists and trainees, respectively, only marginally improved by use of a fixed ROI -0.60, 0.67 and -0.59, 0.49. Intra-class correlation ranged from 0.46 to 0.72. Intra-observer agreement was slightly better and optimised using a fixed ROI-95% limits of agreement -0.52, 0.50 and -0.34, 0.28 for radiologists and trainees, respectively. Intra-class correlation ranged from 0.49 to 0.86. Relative bowel wall signal intensity measurements demonstrate wide limits of observer agreement, unrelated to reader experience but improved using fixed ROIs. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate if experienced readers differ when matching polyps shown by both CT colonography (CTC) and optical colonoscopy (OC) and to explore the reasons for discrepancy. Twenty-eight CTC cases with corresponding OC were presented to eight experienced CTC readers. Cases represented a broad spectrum of findings, not completely fulfilling typical matching criteria. In 21 cases there was a single polyp on CTC and OC; in seven there were multiple polyps. Agreement between readers for matching was analyzed. For the 21 single-polyp cases, the number of correct matches per reader varied from 13 to 19. Almost complete agreement between readers was observed in 15 cases (71%), but substantial discrepancy was found for the remaining six (29%) probably due to large perceived differences in polyp size between CT and OC. Readers were able to match between 27 (71%) and 35 (92%) of the 38 CTC detected polyps in the seven cases with multiple polyps. Experienced CTC readers agree to a considerable extent when matching polyps between CTC and subsequent OC, but non-negligible disagreement exists. [ABSTRACT FROM AUTHOR]

CT colonography (CTC) is increasingly advocated as an effective initial screening tool for colorectal cancer. Nowadays, policy-makers are increasingly interested in cost-effectiveness issues. A number of studies assessing the cost-effectiveness of CTC have been published to date. The majority of findings indicate that CTC is probably not cost-effective when colonoscopy is available, but this conclusion is sensitive to a number of key parameters. This review discusses the findings of these studies, and considers those factors which most influence final conclusions, notably intervention costs, compliance rates, effectiveness of colonoscopy, and the assumed prevalence and natural history of diminutive advanced polyps. [ABSTRACT FROM AUTHOR]

The effect of field of view on mucosal visualisation and reader efficiency during three-dimensional endoluminal CT colonography (CTC) was investigated. Twenty CTC datasets were reviewed at standard 90-degree and "wide" 140-degree viewing angles using customised viewing software (V3D colon; Viatronix), which listed number and size of missed mucosal areas ("missed regions tool") and percentage mucosal visualisation. We compared: (1) unidirectional and bidirectional flythrough using 140- versus 90-degree viewing angles; (2) reader analysis time comparing unidirectional 140-degree flythrough versus bidirectional 90-degree flythrough; (3) paired image snapshots of 12 polyps taken at each field of view were reviewed to assess conspicuity. All patients underwent conventional colonoscopy. Bidirectional 140-degree review reduced the numbers of missed areas by between eight- and 40-fold depending on size category, including those >1,000 mm(2), compared with standard 90-degree bidirectional flythrough (P < 0.001). Combined prone-supine unidirectional 140-degree flythrough and missed area review was 3.8 min faster than 90-degree bidirectional review (9.3 versus 5.5 min, P < 0.0001) for the same surface visualisation. When viewed as pairs, polyps were rated more conspicuous with a 90-degree field of view, P = 0.03. Wide-angle (140-degree) CTC can reduce both numbers of missed areas and review times. However, this may be at the expense of polyp conspicuity. [ABSTRACT FROM AUTHOR]

The purpose was to evaluate the ability of computer-aided detection (CAD) software to detect morphologically flat early colonic carcinoma using CT colonography (CTC). Twenty-four stage T1 colonic carcinomas endoscopically classified as flat (width over twice height) were accrued from patients undergoing staging CTC. Tumor location was annotated by three experienced radiologists in consensus aided by the endosocpic report. CAD software was then applied at three settings of sphericity (0, 0.75, and 1). Computer prompts were categorized as either true positive (overlapping tumour boundary) or false positive. True positives were subclassified as focal or non focal. The 24 cancers were endoscopically classified as type IIa (n=11) and type IIa+IIc (n=13). Mean size (range) was 27 mm (7-70 mm). CAD detected 20 (83.3%), 17 (70.8%), and 13 (54.1%) of the 24 cancers at filter settings of 0, 0.75, and 1, respectively with 3, 4, and 8 missed cancers of type IIa, respectively. The mean total number of false-positive CAD marks per patient at each filter setting was 36.5, 21.1, and 9.5, respectively, excluding polyps. At all settings, >96.1% of CAD true positives were classified as focal. CAD may be effective for the detection of morphologically flat cancer, although minimally raised laterally spreading tumors remain problematic. [ABSTRACT FROM AUTHOR]

The purpose was to determine the accuracy of polyp measurement by endoscopy and CT. A colonic phantom was constructed containing 12 simulated polyps of known diameter. Polyp diameter was estimated during endoscopy by two observers independently. The phantom was then scanned using a 64-detector-row machine and diameter estimated by a further two observers independently, using 2D and 3D visualisation methods. All measurements were obtained twice. Bland-Altman statistics were used to assess agreement between observers' estimates and the reference diameter. The mean difference between observers' measurements and the reference diameter was smallest for estimates made using 3D CT (-0.09 mm and -0.03 mm) and greatest for endoscopy (-1.10 mm and -1.19 mm), with 2D CT intermediate. However, 95% limits of agreement were largest for 3D CT estimates (-4.38 mm to 4.20 mm). Estimates by 2D CT consistently overestimated polyp diameter, whereas endoscopy consistently underestimated diameter. In contrast, measurements by 3D CT were a combination of over- and under-estimates, with a tendency for disagreement to increase with the size of the polyp. The effect of observer experience was small and repeatability was best for 2D CT. Measurement error was encountered with all three modalities tested. Estimates made by 2D CT were believed to offer the best compromise overall. [ABSTRACT FROM AUTHOR]

Social science attempts to incorporate emotions into models of judgment and decision making have faced significant theoretical challenges, as well as produced conflicting empirical results. The following study first contributes to the body of knowledge by providing a theoretical explanation for the observed conflicting results from such models. In fact, both extant theory and the results reported herein suggest that a certain amount of variability in results should be expected from empirical investigations based on such models, particularly related to differences in respondents' level of affective versus cognitive involvement. Second, an argument is presented for considering a special case of Perugini and Bagozzi's (2001) Model of Goal-directed Behaviours (MGBs) when investigating these issues using attitude-based explanations of goal-related behaviours. Specifically, empirical evidence is presented for broadening the MGB model by including anticipated regret as an explanatory variable independent of other anticipated emotions, and deepening the theory by calling for multidimensional conceptualizations of the attitude and perceived behavioural control constructs. The implications of the reported study are presented and discussed. [ABSTRACT FROM AUTHOR]

The following study investigates how physicians in one state (Illinois) attitudinally cope with a recent law mandating physician behaviors. Specifically, this study focuses on OB/GYN physician compliance with The Sexual Assault Survivors Emergency Treatment Act (Public Law 92-156, 2002), which requires hospitals in the state of Illinois to have an approved plan for treating sexual assault survivors. What makes this research setting interesting are the potential linkages between the legal mandate, physician attitudes, and the ongoing controversy concerning abortion. The results of a census of OB/GYN physicians within the state suggest (1) this physician group is largely supportive of the letter and spirit of this law, (2) the emerging attitude models such and Perugini and Bagozzi's (2001) MGB model explaining the formation of behavioral intentions must be treated with caution when generalizing to situations mandating legal behaviors, and (3) moderating influences such as attitude strength and religiosity have no apparent effect in how attitudes relate to physician motivation to comply with such laws. The managerial and research implications of the reported study are presented and discussed. [ABSTRACT FROM AUTHOR]