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Abstract Current treatment outcome of patients with glioblastoma (GBM) remains poor. Following standard therapy, recurrence is universal with limited survival. Tumors from 173 GBM patients are analysed for somatic mutations to generate a personalized peptide vaccine targeting tumor-specific neoantigens. All patients were treated within the scope of an individual healing attempt. Among all vaccinated patients, including 70 treated prior to progression (primary) and 103 treated after progression (recurrent), the median overall survival from first diagnosis is 31.9 months (95% CI: 25.0–36.5). Adverse events are infrequent and are predominantly grade 1 or 2. A vaccine-induced immune response to at least one of the vaccinated peptides is detected in blood samples of 87 of 97 (90%) monitored patients. Vaccine-specific T-cell responses are durable in most patients. Significantly prolonged survival is observed for patients with multiple vaccine-induced T-cell responses (53 months) compared to those with no/low induced responses (27 months; P = 0.03). Altogether, our results highlight that the application of personalized neoantigen-targeting peptide vaccine is feasible and represents a promising potential treatment option for GBM patients.

Introduction Pain and disability after meniscectomy can be a substantial lifelong problem. There are few treatment options, especially for young people. Non-surgical management (rehabilitation) is an option but increasingly surgeons are performing meniscal allograft transplants (MATs) for these individuals. However, this is still an uncommon procedure, and availability and usage of MAT vary widely both in the UK and internationally. It is not known which treatment option is the most effective and cost-effective.Methods and analysis The Meniscal Transplant surgery or Optimised Rehabilitation trial is an international, multicentre, randomised controlled trial. The aim is to compare the clinical and cost effectiveness of MAT versus an optimised package of individualised, progressive, rehabilitation that we have called personalised knee therapy (PKT).Participants will be recruited from sites across the UK, Australia, Canada and Belgium. The planned 144 participants provide at least 90% power to detect a 10-point difference in the Knee injury and Osteoarthritis Outcome Score (KOOS4) at 24-months post randomisation (primary outcome). A prospectively planned economic evaluation will be conducted from a healthcare system and personal social services perspective. Secondary outcome data including health utility, occupational status, sports participation, mental well-being, further treatment, and adverse events will be collected at 3, 6, 12, 18, and 24 months. Analysis will be on an intention-to-treat basis and reported in-line with the Consolidated Standards of Reporting Trials statement.Ethics and dissemination The trial was approved by the London—Bloomsbury Research Ethics Committee on 19 August 2022 (22/LO/0327) and Northern Sydney Local Health District Human Research Ethics Committee, NSW, Australia on the 13 March 2023 (2022/ETH01890).Trial results will be disseminated via peer-reviewed publications, presentations at international conferences, in lay summaries and using social media as appropriate.This protocol adheres to the recommended Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) checklist.Trial registration number ISRCTN87336549.

Abstract The notion that phonons can carry pseudo‐angular momentum has many major consequences, including topologically protected phonon chirality, Berry curvature of phonon band structure, and the phonon Hall effect. When a phonon is resonantly coupled to an orbital state split by its crystal field environment, a so‐called vibronic bound state forms. Here, a vibronic bound state is observed in NaYbSe2, a quantum spin liquid candidate. In addition, field and polarization dependent Raman microscopy is used to probe an angular momentum transfer of ΔJz = ±ℏ between phonons and the crystalline electric field mediated by the vibronic bound stat. This angular momentum transfer between electronic and lattice subsystems provides new pathways for selective optical addressability of phononic angular momentum via electronic ancillary states.

Abstract Background Isolated ACL reconstructions (ACLR) demonstrate limitations in restoring native knee kinematics. This study investigates the knee mechanics of ACLR plus various anterolateral augmentations using a patient-specific musculoskeletal knee model. Materials and methods A patient-specific knee model was developed in OpenSim using contact surfaces and ligament details derived from MRI and CT data. The contact geometry and ligament parameters were varied until the predicted knee angles for intact and ACL-sectioned models were validated against cadaveric test data for that same specimen. Musculoskeletal models of the ACLR combined with various anterolateral augmentations were then simulated. Knee angles were compared between these reconstruction models to determine which technique best matched the intact kinematics. Also, ligament strains calculated by the validated knee model were compared to those of the OpenSim model driven by experimental data. The accuracy of the results was assessed by calculating the normalised RMS error (NRMSE); an NRMSE 60%). Similar errors were observed between ACL strain results (NRMSE > 60%). Other ligament comparisons were acceptable. All ACLR plus anterolateral augmentation models restored kinematics toward the intact state, with ACLR plus anterolateral ligament reconstruction (ACLR + ALLR) achieving the best match and the greatest strain reduction in ACL, PCL, MCL, and DMCL. Conclusion The intact and ACL-sectioned models were validated against cadaveric experimental results for all rotations. It is acknowledged that the validation criteria are very lenient; further refinement is required for improved validation. The results indicate that anterolateral augmentation moves the kinematics closer to the intact knee state; combined ACLR and ALLR provide the best outcome for this specimen.

Despite decades of research and clinical trials, metastatic castration-resistant prostate cancer (mCRPC) remains incurable and typically fatal. Current treatments may provide modest increases in progression-free survival but can come with significant adverse effects and are disaggregated from the diagnostic imaging needed to fully assess the spread of metastatic disease. A theranostic approach, using radiolabeled ligands that target the cell surface protein PSMA, simplifies the visualization and disease treatment process by enabling both to use similar agents. Here, we describe an exemplary case wherein a gentleman in his 70s with mCRPC on diagnosis was treated with 177Lu–PSMA-617 and abiraterone, and remains disease-free to date, over five years later.

Este texto fue originalmente publicado por David S. Parker en el año 1998 como introducción al libro The Idea of the Middle Class: White-Collar Workers and Peruvian Society, 1900-1950, publicado por la editorial Penn State University. En él, el autor reflexiona sobre la sindicación de los empleados de Lima (Perú) y sobre el origen de la ley de 1924 que estableció una distinción legal entre empleado y obrero. Tanto la escuela «constructivista» como el giro lingüístico plantean que las clases sociales son abstracciones, inventos del imaginario colectivo, es decir, ideas que compiten en un mercado ideológico. De entre las infinitas maneras de conceptualizar la sociedad solo unas cuantas imágenes y discursos llegan a convertirse en sentido común, influyendo en la formación de identidades e inspirando leyes y políticas públicas. El presente texto afirma y caracteriza que la formación del concepto clase media en el Perú se debe a procesos ideológicos, discursivos y políticos.

Abstract Objective The primary aim of the present study was to evaluate the long-term outcomes including survivorship of computer navigated distal femoral lateral opening wedge osteotomy (DFLOWO). The secondary aim was to identify the potential factors that may influence its survivorship. Methods A retrospective analysis of prospectively collected data for patients with lateral compartment arthritis who underwent navigated DFLOWO from December 2006 to November 2012 was performed. The International Knee Documentation Committee (IKDC) and Knee Injury and Osteoarthritis Outcome Score (KOOS) scores were analyzed for outcome measures. Conversion to arthroplasty during the follow-up was the end point. Results A total of 19 DFLOWOs were performed in 17 patients with a mean age of 46.6 ± 6.5 years formed the study cohort. The coronal alignment was corrected from a mean of 7.1° (2-11°) valgus to a mean of 2.1° (0.5°-3°) varus. The IKDC scores improved from mean of 39 preoperatively to 53 at the mean long-term follow-up of 9.1 years. The mean KOOS scores at the long-term follow-up were pain 71, symptoms 56, activities of daily living 82, sports and recreation 59, quality of life 43. Survivorship of the DFLOWO was 78.9% at a follow-up of 9.1 years. Presence of ≥ grade 2 according to the International Cartilage Repair Society (ICRS) cartilage degeneration in the medial compartment of the knee and >7° preoperative valgus deformity were strongly correlated with conversion to total knee arthroplasty (TKA) at the long-term follow-up (r= 0.66). ConclusionsComputer navigated DFLOWO has satisfactory clinical outcomes and 79% survivorship in long-term follow-up. Presence of more than ICRS ≥ grade 2 degenerative changes in the medial compartment of knee with > 7° preoperative valgus deformity negatively affects the survivorship of DFLOWO in the long-term follow-up.

Here, the authors introduce a live-cell imaging system using chiroptical contrast, enabling the study of chiral interactions. They demonstrate simultaneous imaging of enantiomeric pairs of molecular probes emitting circularly polarised light, using both single and two-photon excitation.

While the anatomical properties of regenerated axons across spinal cord lesion sites have been studied extensively, little is known of how the functional properties of regenerated synapses compared to those in unlesioned animals. This study aims to compare the properties of synapses made by regenerated axons with unlesioned axons using the lamprey, a model system for spinal injury research, in which functional locomotor recovery after spinal cord lesions is associated with axonal regeneration across the lesion site. Regenerated synapses below the lesion site did not differ from synapses from unlesioned axons with respect to the amplitude and duration of single excitatory postsynaptic potentials. They also showed the same activity-dependent depression over spike trains. However, regenerated synapses did differ from unlesioned synapses as the estimated number of synaptic vesicles was greater and there was evidence for increased postsynaptic quantal amplitude. For axons above the lesion site, the amplitude and duration of single synaptic inputs also did not differ significantly from unlesioned animals. However, in this case, there was evidence of a reduction in release probability and inputs facilitated rather than depressed over spike trains. Synaptic inputs from single regenerated axons below the lesion site thus do not increase in amplitude to compensate for the reduced number of descending axons after functional recovery. However, the postsynaptic input was maintained at the unlesioned level using different synaptic properties. Conversely, the facilitation from the same initial amplitude above the lesion site made the synaptic input over spike trains functionally stronger. This may help to increase propriospinal activity across the lesion site to compensate for the lesion-induced reduction in supraspinal inputs. The animal experiments were approved by the Animal Ethics Committee of Cambridge University.

Seaweeds are macroalgae, which can be of many different morphologies, sizes, colors, and chemical profiles. They include brown, red, and green seaweeds. Brown seaweeds have been more investigated and exploited in comparison to other seaweed types for their use in animal feeding studies due to their large sizes and ease of harvesting. Recent in vitro and in vivo studies suggest that plant secondary compound-containing seaweeds (e.g., halogenated compounds, phlorotannins, etc.) have the potential to mitigate enteric methane (CH4) emissions from ruminants when added to the diets of beef and dairy cattle. Red seaweeds including Asparagopsis spp. are rich in crude protein and halogenated compounds compared to brown and green seaweeds. When halogenated-containing red seaweeds are used as the active ingredient in ruminant diets, bromoform concentration can be used as an indicator of anti-methanogenic properties. Phlorotannin-containing brown seaweed has also the potential to decrease CH4 production. However, numerous studies examined the possible anti-methanogenic effects of marine seaweeds with inconsistent results. This work reviews existing data associated with seaweeds and in vitro and in vivo rumen fermentation, animal performance, and enteric CH4 emissions in ruminants. Increased understanding of the seaweed supplementation related to rumen fermentation and its effect on animal performance and CH4 emissions in ruminants may lead to novel strategies aimed at reducing greenhouse gas emissions while improving animal productivity.

Scientific reductionism, the view that higher level functions can be explained by properties at some lower-level or levels, has been an assumption of nervous system analyses since the acceptance of the neuron doctrine in the late 19th century, and became a dominant experimental approach with the development of intracellular recording techniques in the mid-20th century. Subsequent refinements of electrophysiological approaches and the continual development of molecular and genetic techniques have promoted a focus on molecular and cellular mechanisms in experimental analyses and explanations of sensory, motor, and cognitive functions. Reductionist assumptions have also influenced our views of the etiology and treatment of psychopathologies, and have more recently led to claims that we can, or even should, pharmacologically enhance the normal brain. Reductionism remains an area of active debate in the philosophy of science. In neuroscience and psychology, the debate typically focuses on the mind-brain question and the mechanisms of cognition, and how or if they can be explained in neurobiological terms. However, these debates are affected by the complexity of the phenomena being considered and the difficulty of obtaining the necessary neurobiological detail. We can instead ask whether features identified in neurobiological analyses of simpler aspects in simpler nervous systems support current molecular and cellular approaches to explaining systems or behaviors. While my view is that they do not, this does not invite the opposing view prevalent in dichotomous thinking that molecular and cellular detail is irrelevant and we should focus on computations or representations. We instead need to consider how to address the long-standing dilemma of how a nervous system that ostensibly functions through discrete cell to cell communication can generate population effects across multiple spatial and temporal scales to generate behavior.

OBJECTIVES/GOALS: 22q.11 deletion syndrome (22q11DS) is a genomic syndrome that elevates risk for psychosis >20-fold. We used a battery of cognitive and psychophysiological psychosis-risk biomarkers in 22q11DS patients and healthy subjects in order to identify biomarkers of psychosis in 22q11DS that could be used as translational targets in intervention studies. METHODS/STUDY POPULATION: We recruited 15 22q11DS individuals (Mean age=30, M/F=9/6) and 19 healthy controls (HCs; Mean age=34, M/F=5/14). Each individual completed the MATRICS Consensus Cognitive Battery (MCCB), the Wechsler Abbreviated Scale of Intelligence, Second edition (WASI-II) Verbal IQ subtests, and the computerized Wisconsin Card Sorting Task (WCST). To examine auditory EEG responses, each participant completed the 'Double-Deviant' target detection paradigm, which presents a pseudorandom sequence of frequent standard tones and infrequent deviant tones. Mismatch negativity (MMN) metrics were generated from this assessment. Welch's t-tests were completed for neurocognitive variables. One-Way ANOVAs were completed to examine EEG results, with sex entered as a separate factor and age entered as a covariate. RESULTS/ANTICIPATED RESULTS: Significant group differences were found in 8 of the 9 neurocognitive measurements (FDR-adjusted p's< 0.02, average Cohen's d=1.62, average observed power= 0.91) indicating widespread cognitive deficits in 22q11DS subjects across multiple domains. The Double-Deviant MMN ERP response was significantly smaller in absolute magnitude in the 22q11DS group (FDR-adjusted p=0.048, Cohen’s d= -0.864, observed power= 0.58). The MMN ERPs for the frequency and duration deviants were not significantly different (FDR-adjusted p's> 0.33). No group by sex interactions were observed in any of the measures. Neurocognitive variables were associated with psychosis positive, negative, general, and disorganized symptom scales. DISCUSSION/SIGNIFICANCE: Our results identify potential psychosis-risk biomarkers in 22q11DS. If replicated, these biomarkers could provide important translational targets for future clinical trials for individuals with 22q11DS and other individuals at-risk for psychosis syndromes.

Abstract Modern molecular techniques enable characterization of the microbial biome in livestock manure, from which there is particular concern over emission of greenhouse gases. This study evaluated how sampling depth, time, temperature, and artificial rainfall affected microbial community structure in feedyard manure, and relationships between the manure biome and known parameters related to nitrous oxide (N2O) emissions. In three large incubation chambers, maintained at different temperatures that received two applications of artificial rainfall, we evaluated manure microbiome composition and abundance of N2O‐producing enzymes (nirK and nirS) using quantitative polymerase chain reaction (qPCR). These data were used with previously published data from the same study on N2O emissions and assessment of manure physicochemical properties, denitrification enzyme activity (DEA), and nitrification activity (NA). Microbiome composition was Firmicutes (50%), followed by 32% Actinobacteria, 11% Proteobacteria, 5% Bacteroidetes, 1% Chloroflexi, and small populations (

Methane gas from livestock production activities is a significant source of greenhouse gas (GHG) emissions which have been shown to influence climate change. New technologies offer a potential to manipulate the rumen biome through genetic selection reducing CH4 production. Methane production may also be mitigated to varying degrees by various dietary intervention strategies. Strategies to reduce GHG emissions need to be developed which increase ruminant production efficiency whereas reducing production of CH4 from cattle, sheep, and goats. Methane emissions may be efficiently mitigated by manipulation of natural ruminal microbiota with various dietary interventions and animal production efficiency improved. Although some CH4 abatement strategies have shown efficacy in vivo, more research is required to make any of these approaches pertinent to modern animal production systems. The objective of this review is to explain how anti-methanogenic compounds (e.g., plant tannins) affect ruminal microbiota, reduce CH4 emission, and the effects on host responses. Thus, this review provides information relevant to understanding the impact of tannins on methanogenesis, which may provide a cost-effective means to reduce enteric CH4 production and the influence of ruminant animals on global GHG emissions.

Abstract Background Total knee arthroplasty (TKA) is a successful treatment for tricompartmental knee arthritis. Computer navigation and robotic-assisted-surgery (RAS) have emerged as tools that aim to help plan and execute surgery with greater precision and consistency. We reviewed the most current literature to describe the historical background and outcomes compared to conventional TKA. Methods A review and synthesis of the literature comparing the patient reported outcomes (PROM’s) of RA TKA and computer-assisted (CA) TKA to conventional TKA was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results CAS TKA improves accuracy and consistency of implant position, and appears to provide a small improvement in PROMs and implant survival compared to conventional TKA. RTKA similarly improves implant accuracy compared to conventional techniques and early results suggest a similar small benefit in PROMs compared to conventional TKA. A strengthening trend is emerging showing CAS TKA has greatest benefit to implant survival in people under 65. RTKA survival analysis data is more limited and early results do not allow strong conclusions, however early trends are similar to CAS TKA. Conclusion Results for CAS-TKA show improvement in alignment, and early clinical outcomes have revealed promising results, with longer-term data and medium-term survival analysis recently emerging showing small benefits over conventional TKA. RTKA represents another phase of development. Early results show similar trends to that of CAS TKA with longer-term data still to come.

Circular polarization luminescence (CPL) spectroscopy is a tool to study chiroptical systems, but the measurement process is generally very slow. The authors introduce a CPL technique with much faster acquisition, demonstrating meaningful time-dependent measurements and enabling new applications.

The objectives of this study were to (1) examine the effects of plant condensed (CT) and hydrolyzable tannin (HT) extracts on CH4 and N2O emissions; (2) identify the reactions responsible for manure-derived GHG emissions, and (3) examine accompanying microbial community changes in fresh dairy manure. Five treatments were applied in triplicate to the freshly collected dairy manure, including 4% CT, 8% CT, 4% HT, 8% HT (V/V), and control (no tannin addition). Fresh dairy manure was placed into 710 mL glass incubation chambers. In vitro composted dairy manure samples were collected at 0, 24, 48, and 336 h after the start of incubation. Fluxes of N2O and CH4 were measured for 5-min/h for 14 d at a constant ambient incubation temperature of 39 °C. The addition of quebracho CT significantly decreased the CH4 flux rates compared to the tannin-free controls (215.9 mg/m2/h), with peaks of 75.6 and 89.6 mg/m2/h for 4 and 8% CT inclusion rates, respectively. Furthermore, CT significantly reduced cumulative CH4 emission by 68.2 and 57.3% at 4 and 8% CT addition, respectively. The HT treatments failed to affect CH4 reduction. However, both CT and HT reduced (p < 0.001) cumulative and flux rates of N2O emissions. The decrease in CH4 flux with CT was associated with a reduction in the abundance of Bacteroidetes and Proteobacteria.

Paired-stimuli (S1-S2) procedures have long been used to assess auditory processing in psychosis. Such studies have shown aberrant evoked responses (ERPs) following long (S1 response) and/or short (S2 response) inter-stimulus intervals. The historical tendency from paired stimuli outcomes in the schizophrenia (SZ) literature is for (i) response to the first stimulus (S1) to be smaller among SZ, and (ii) response to the second stimulus (S2) to be larger among SZ in relation to the size of their S1. An interpretation of these two findings is that SZ have poor auditory response suppression to redundant stimuli (“poor gating”). The present study sought to determine if the reported S1 and S2 effects in SZ (smaller S1 and larger S2 in relation to S1 magnitude) require the paired-stimuli presentation format. Participants (18 schizophrenia and 17 healthy persons) were administered the equivalent of S1 (after a 4.5-sec ISI – “long ISI”) and S2 (after a 500-ms ISI – “short ISI”) stimuli under four conditions (traditional paired long and short, randomly interleaved long and short, block of long, block of short). Neural activity differences were consistent between-groups independent of condition: (i) schizophrenia cases had greater activity in the pre-stimulus to very early post-stimulus period, (ii) healthy persons had greater M100 activity to long ISI stimuli, and (iii) healthy persons had greater activity after the M50/M100 evoked fields (recovery phase) following short ISI stimuli. Simple early auditory processing in psychosis may be largely independent of stimulus presentation condition, an outcome that may help re-frame future translational studies. Traditional paired-stimuli auditory neural response effects may not require the paired-stimuli format.

Abstract Background Radial meniscus tears can cause the meniscus to be completely incompetent. This serious type of meniscus tear can be difficult to repair. Techniques have been developed that juxtapose the meniscus tear edges and are able to withstand high loads. The purpose of this study was to determine the load to failure of a reinforced suture bar repair (Rebar Repair) for radial meniscus tear and compare it to the parallel suture technique and cross-stitch technique and to compare mode of failure among all three groups. The hypothesis was that the Rebar Repair will have a higher load to failure than both the parallel technique and the cross-stitch technique and that the Rebar Repair would have a lower rate of suture cutting through the meniscus. Methods Forty-eight menisci were tested from 24 human knee specimens, with 16 menisci in each group evenly distributed between medial and lateral menisci. Radial mid body meniscal tears were recreated and repaired with one of three inside-out techniques: the 2-parallel suture technique, 2 cross-stitch sutures, and the Rebar Repair. The specimens were cycled between 5 N to 30 N and axially loaded to failure perpendicularly across the repair site. Results The average load to failure of the parallel group, cross-stitch group and Rebar Repair was 85.5 N ± 22.0, 76.2 N ± 28.8 and 124.1 N ± 27.1 respectively. The Rebar Repair had a higher load to failure than the parallel group (p

Background/objective: Standing balance has become an important clinical measure in patient populations who are at risk of falls or have osteoarthritis. With custom-written software, the Wii Balance Board (WBB) has been shown to be a valid and reliable force platform that can be used to assess standing balance. However, no studies to date have assessed the use of the more readily available Wii Stillness Score (WSS) as a measure of balance. Methods: Twenty-four individuals without lower limb pathology performed a combination of unilateral and double leg standing balance tests with eyes open or closed on two separate occasions. At each session, data from the WBB were acquired on a laptop computer running custom software and then by Wii-Fit software on a Wii console. The reliability of the WSS was determined by assessing reproducibility, while the validity of the WSS was determined by comparing the results of the WSS to that of the custom-written software. Results: We found that the WSS exhibited excellent intra and inter device reliability in three out of four stances tested. The Bland-Altman plots also showed good concurrent validity for the three analysed stances. However, there remain significant limitations with the use of the WSS such as its rigid thirty-second time parameter and single score result. Conclusion: The readily available WBB may be a used as a portable and inexpensive device to assess standing balance with custom written software. However, with the current limitations of the WSS, we would discourage its use as a clinical measure of balance. Keywords: Wii-fit, Standing, Balance, Stillness score, Wii balance board, CoP

Relaxation of predation pressure following the removal of mammalian predators has led to the irruption of large herbivores and excessive levels of herbivory in many regions of the Earth. Conservation reserves in dryland regions aim to restore ecological processes and facilitate biodiversity conservation by functioning as refuges from grazing by livestock. However, grazing pressure in conservation reserves may be high and hamper conservation objectives because wild herbivore populations have irrupted in the surrounding landscape due to predator control as well as the absence of hunting and competition with livestock within reserves. Here, we assess the relative abundance of native herbivores (kangaroos) and introduced herbivores (rabbits) using driving transects and dung surveys, and use selective exclosures to assess wild herbivores’ impacts on vegetation and soils in four conservation reserves in semi-arid Australia. Kangaroos were the dominant herbivore in each reserve. Grazing by kangaroos and/or rabbits was linked to reduced complexity of understorey vegetation, grass cover, species richness of grasses, forbs and shrubs, the depletion of soil carbon and phosphorous, and increased soil bulk density. The marked impacts of grazing by wild herbivores, particularly kangaroos, on vegetation and soils that we report are symptomatic of overgrazing. Our study provides evidence that grazing by kangaroos may jeopardize conservation efforts across a large region of semi-arid Australia. We contend that managing the total grazing pressure exerted by wild herbivores is crucial to prevent overgrazing in dryland conservation reserves where herbivore populations are not regulated by predators.

Schwannomas and Perineuromas are rare findings in the GI tract, especially in pediatric patients. They typically present in the fifth to sixth decade of life with a female predominance. In this case, we describe a 13-year-old female who presented with multiple GI complaints including weight loss and anemia. She was found to have an umbilicated mass in the lesser curvature of the stomach suspicious of a gastrointestinal stromal tumor (GIST). The mass was resected via a laparoscopic partial gastrectomy. The pathology report confirmed the diagnosis of a gastric hybrid schwannoma and perineuroma staining for EMA and S-100 protein.

A key challenge in the field of cognitive neuroscience is to identify discriminable cognitive functions, and then map these functions to brain activity. In the current study, we set out to explore the relationships between performance arising from different cognitive tasks thought to tap different domains of cognition, and then to test whether these distinct latent cognitive abilities also are subserved by corresponding "latent" brain substrates. To this end, we tested a large sample of adults under the age of 40 on twelve cognitive tasks as they underwent fMRI scanning. Exploratory factor analysis revealed 4-factor model, dissociating tasks into processes corresponding to episodic memory retrieval, reasoning, speed of processing and vocabulary. An analysis of the topographic covariance patterns of the BOLD-response acquired during each task similarity also converged on four neural networks that corresponded to the 4 latent factors. These results suggest that distinct ontologies of cognition are subserved by corresponding distinct neural networks.

Intro: The Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) proposed “Biotypes,” subgroups of psychosis cases with neuro-cognitive homology. Neural activity unbound to stimulus processing (nonspecific or intrinsic activity) was important for differentiating Biotypes, with Biotype-2 characterized by high nonspecific neural activity. A precise estimate of intrinsic activity (IA) was not included in the initial Biotypes characterization. This report hypothesizes intrinsic activity is a critical differentiating feature for psychosis Biotypes. Method: Participants were recruited at B-SNIP sites and included probands with psychosis (schizophrenia, schizoaffective disorder, bipolar I disorder), their first-degree biological relatives, and healthy persons (N = 1338). Probands were also sub-grouped by psychosis Biotype. 10-sec inter-stimulus intervals during an auditory paired-stimuli task were used to quantify intrinsic activity from 64 EEG sensors. Single-trial power and connectivity measures at empirically derived frequency bands were quantified. Multivariate discriminant and correlational analyses were used to summarize variables that efficiently and maximally differentiated groups by conventional diagnoses and Biotypes and to determine their relationship to clinical and social functioning. Results: Biotype-1 consistently exhibited low IA, and Biotype 2 exhibited high IA relative to healthy persons across power frequency bands (delta/theta, alpha, beta, gamma) and alpha band connectivity estimates. DSM groups did not differ from healthy persons on any IA measure. Discussion: Psychosis Biotypes, but not DSM syndromes, were differentiated by intrinsic activity; Biotype-2 was uniquely characterized by an accentuation of this measure. Neurobiologically defined psychosis subgroups may facilitate the use of intrinsic activity in translation models aimed at developing effective treatments for psychosis-relevant deviations in neural modulation.

Background and study aims Biliary access following Roux-en-Y gastric bypass (RYGB) anatomy presents a significant challenge. Long-term outcomes of laparoscopic-assisted trans-gastric ERCP (LA-ERCP) including sphincter of Oddi dysfunction (SOD) subtypes have not been thoroughly examined. Our study aims to present our overall outcomes of trans-gastric LAERCP and examine a significant subgroup of patients with SOD after RYGB. Patients and methods A retrospective review of RYGB patients who underwent LA-ERCP between 2009 and 2016 identified 51 patients. A subgroup of 22 patients with SOD were examined and contacted by phone survey to determine long-term symptom resolution. Results Post-procedure length of stay was 1.9 days (SD 3.0). There was one conversion from laparoscopic to open procedure. Selective cannulation rate was 100 %. Mean follow-up was 14.6 months. There were two major operative complications, two major ERCP-related complications, and five wound infections (9.8 %). No deaths or episodes of pancreatitis occurred. Seventeen patients had biliary SOD (Type I = 9, Type II = 8). The remaining four had pancreatic SOD (Type I = 1, Type II = 4). SOD subgroup follow-up was 21.4 months (SD 18.1). All patients with Type I biliary and 75 % with Type I pancreatic SOD reported complete resolution of their symptoms. Conclusions Consistent with other published series, LA-ERCP yields excellent cannulation rates after RYGB. Successful treatment of pancreatic and Type 1 biliary SOD suggests that there is significant symptomatic benefit to treating this patient population. However, an overall complication rate of approximately 15 % with LAERCP leaves open the possibility for improvements in access techniques in post-RYGB patients.

Mutations or other alterations in the RET gene have been implicated in a variety of malignancies – most commonly thyroid, but also chronic myelomonocytic leukemia, acute myeloid leukemia, and lung, breast, pancreatic, and colon cancers. Here we present a case of a gentlemen initially diagnosed with and treated for non-small cell lung adenocarcinoma. Genomic profiling of his tumor specimen revealed a RET point mutation with a known association with medullary thyroid cancer (MTC). Further pathological and molecular diagnostic evaluation confirmed a diagnosis of MTC, leading to a change in treatment from standard chemotherapy for non-small cell lung cancer to targeted therapy against RET and potential implications regarding inherited cancer risk for his offspring. The patient experienced a clinical response to treatment and several months of improved quality of life. This case illustrates the capacity of genomic profiling to uncover molecular drivers of disease and help ensure proper diagnosis and management of cancer.

The engagement observed by the players of the games that they play is a desirable quality that has not gone unnoticed in the field of education, leading to concepts such as gamification of education, game-based learning and serious games for training. Game designer Sid Meier is often cited as defining games as being ‘a series of interesting decisions’. The concept of choice implies an autonomous selection from a constrained set of options. This article reflects on the impact of autonomy and constraints, and extrinsic and intrinsic motivators on students’ software development work during both curricular and extracurricular activities. Finally, a model for the design of games for game-based learning is proposed in terms of autonomy and constraints with respect to learning outcomes.

This paper presents details of Mg-assisted flux growth of Sm2Co17 single crystals in a Ta crucible well below the melting temperature of binary Sm2Co17. Both the crushed single crystalline powder x-ray diffraction (XRD) and single crystalline XRD data revealed the Th2Zn17 type rhombohedral(R-3m) crystal structure. Ta atom is found to be statistically replacing the Co-Co dumbbell with its position being at the center of the dumbbell. The Curie temperature of our lightly Mg and Ta doped Sm2Co17 sample is determined to be ∼1100 K using method of generalized Bloch law fitting of easy axis spontaneous magnetization data.

It is now accepted that neurons contain and release multiple transmitter substances. However, we still have only limited insight into the regulation and functional effects of this co-transmission. Given that there are 200 or more neurotransmitters, the chemical complexity of the nervous system is daunting. This is made more-so by the fact that their interacting effects can generate diverse non-linear and novel consequences. The relatively poor history of pharmacological approaches likely reflects the fact that manipulating a transmitter system will not necessarily mimic its roles within the normal chemical environment of the nervous system (e.g., when it acts in parallel with co-transmitters). In this article, co-transmission is discussed in a range of systems [from invertebrate and lower vertebrate models, up to the mammalian peripheral and central nervous system (CNS)] to highlight approaches used, degree of understanding, and open questions and future directions. Finally, we offer some outlines of what we consider to be the general principles of co-transmission, as well as what we think are the most pressing general aspects that need to be addressed to move forward in our understanding of co-transmission.

Abstract Background The widespread acceptance and application of 68Ga-PET depends on our ability to develop radiopharmaceuticals that can be prepared in a convenient and suitable manner. A kit-type labelling protocol provides such characteristics and requires chelators that can be radiolabelled under exceptionally mild conditions. Recently the DATA chelators have been introduced that fulfil these requirements. In continuing their development, the synthesis and radiolabelling of the first DATA bifunctional chelator (BFC) and peptide conjugate are described. Results A BFC derived from the DATA ligand (2,2’-(6-((carboxymethyl)amino)-1,4-diazepane-1,4-diyl)diacetic acid) has been synthesised in five steps from simple building blocks, with an overall yield of 8 %. DATAM5-3tBu (5-[1,4-Bis-tert-butoxycarbonylmethyl-6-(tert-butoxycarbonylmethyl-methyl-amino)-[1, 4]diazepan-6-yl]-pentanoic acid) has been coupled to [DPhe1][Tyr3]-octreotide (TOC) and the resulting peptide conjugate (DATATOC) radiolabelled with purified 68Ga derived via four different 68Ge/68Ga generator post-processing (PP) methods. The stability and lipophilicity of the radiotracer have been assessed and a kit-type formulation for radiolabelling evaluated. 68Ga-DATATOC has been prepared with a > 95 % radiochemical yield (RCY) within 1 (fractionated and acetone-PP) and 10 min (ethanol- and NaCl-PP) at 23 °C (pH 4.2–4.9, 13 nmol). The radiolabelled peptide is stable in the presence of human serum. Lipophilicity of 68Ga-DATATOC was calculated as logP = −3.2 ± 0.3, with a HPLC retention time (t R = 10.4 min) similar to 68Ga-DOTATOC (logP = −2.9 ± 0.4, t R = 10.3 min). Kit-type labelling from a lyophilised solid using acetone-PP based labelling achieves > 95 % RCY in 10 min at 23 °C. Conclusions The favourable labelling properties of the DATA chelators have been retained for DATATOC. High radiochemical purity can be achieved at 23 °C in less than 1 min and from a kit formulation. The speed, reliability, ease, flexibility and simplicity with which 68Ga-DATATOC can be prepared makes it a very attractive alternative to current standards.

This article describes two complementary OA (open access) initiatives launching in 2016 at Alexander Street. Contributing Collections will see 10% of all revenue generated dedicated to digitizing and making OA important archives. Premium Services offer member libraries the opportunity to upload and make OA locally generated content. While this article focuses on the discipline of anthropology, Alexander Street will extend these two models into history, music and theater later in 2016.

Governments across the West have invested significant resources in preventing radicalization, and strategies to prevent and counter violent extremism (P/CVE) are increasingly prominent within wider counter-terrorism policies. However, we know little about their effects, especially about projects that utilize former extremists to counter extremist narratives and increase critical thinking. Despite the prominence of interventions utilizing “formers”, there are almost no systematic, scientific evaluations of these programs. The lack of evaluation is problematic given the recognized risks and negative effects of using formers to address other social issues, such as crime prevention. This paper presents findings from the largest study to date of the effects of using former extremists to prevent violent extremism. Based on a randomized controlled effect evaluation with 1931 Danish youths, it highlights significant successes, including reducing the perceived legitimacy of political violence, as well as negative effects, including a small decrease in political tolerance. Overall, the findings suggest a need for cost–benefit analyses of P/CVE initiatives, weighing the benefits against the risks.

Finding a treatment for spinal cord injury (SCI) focuses on reconnecting the spinal cord by promoting regeneration across the lesion site. However, while regeneration is necessary for recovery, on its own it may not be sufficient. This presumably reflects the requirement for regenerated inputs to interact appropriately with the spinal cord, making sub-lesion network properties an additional influence on recovery. This review summarizes work we have done in the lamprey, a model system for SCI research. We have compared locomotor behavior (swimming) and the properties of descending inputs, locomotor networks, and sensory inputs in unlesioned animals and animals that have received complete spinal cord lesions. In the majority (∼90%) of animals swimming parameters after lesioning recovered to match those in unlesioned animals. Synaptic inputs from individual regenerated axons also matched the properties in unlesioned animals, although this was associated with changes in release parameters. This suggests against any compensation at these synapses for the reduced descending drive that will occur given that regeneration is always incomplete. Compensation instead seems to occur through diverse changes in cellular and synaptic properties in locomotor networks and proprioceptive systems below, but also above, the lesion site. Recovery of locomotor performance is thus not simply the reconnection of the two sides of the spinal cord, but reflects a distributed and varied range of spinal cord changes. While locomotor network changes are insufficient on their own for recovery, they may facilitate locomotor outputs by compensating for the reduction in descending drive. Potentiated sensory feedback may in turn be a necessary adaptation that monitors and adjusts the output from the “new” locomotor network. Rather than a single aspect, changes in different components of the motor system and their interactions may be needed after SCI. If these are general features, and where comparisons with mammalian systems can be made effects seem to be conserved, improving functional recovery in higher vertebrates will require interventions that generate the optimal spinal cord conditions conducive to recovery. The analyses needed to identify these conditions are difficult in the mammalian spinal cord, but lower vertebrate systems should help to identify the principles of the optimal spinal cord response to injury.