Cognitive deficits in schizophrenia : their nature and impact on daily life

This research provides further support for the existence of differential cognitive impairments in schizophrenia and especially for the presence of disproportionate attentional deficits.The results add credibility to the view that attentional disorders are responsible for many of the problems of everyday living in schizophrenia. Crucially these findings are the first to demonstrate in a schizophrenic sample a clear relationship between attentional deficits measured by objective tests and those measured by independent ratings. This project is also the first to show that attentional deficits account for a substantial proportion of the variance in social and interpersonal functioning even after controlling for the potential contribution of a comprehensive range of other factors, including negative symptoms. This study shows that schizophrenics are acutely aware of having cognitive difficulties. However the research confirms previous findings with a diverse range of samples showing that the subjective judgements do not correlate with performance on cognitive tests nor with independent ratings of cognitive functioning. However, as predicted it was also shown that self ratings of cognitive efficacy are related to dysphoric mood, greater use of avoidant coping methods, and a failure to use active coping strategies. This suggests a possible vicious cycle of helplessness which may be amenable to therapeutic interventions.The present findings indicate the potential value of using comprehensive assessments of cognitive functioning as a part of the routine clinical assessment procedure for schizophrenic patients. Assessments based on existing symptom rating scales do not adequately describe the impairments faced by someone living with schizophrenia, nor how these deficits interfere so profoundly with the tasks of daily life.Such detailed assessments of cognitive functioning may in the future help to guide cognitive and environmental interventions aimed at improving the well being, coping and functioning of those who have to endure this illness

H-Packer: Holographic Rotationally Equivariant Convolutional Neural Network for Protein Side-Chain Packing

Accurately modeling protein 3D structure is essential for the design of functional proteins. An important sub-task of structure modeling is protein side-chain packing: predicting the conformation of side-chains (rotamers) given the protein's backbone structure and amino-acid sequence. Conventional approaches for this task rely on expensive sampling procedures over hand-crafted energy functions and rotamer libraries. Recently, several deep learning methods have been developed to tackle the problem in a data-driven way, albeit with vastly different formulations (from image-to-image translation to directly predicting atomic coordinates). Here, we frame the problem as a joint regression over the side-chains' true degrees of freedom: the dihedral $\chi$ angles. We carefully study possible objective functions for this task, while accounting for the underlying symmetries of the task. We propose Holographic Packer (H-Packer), a novel two-stage algorithm for side-chain packing built on top of two light-weight rotationally equivariant neural networks. We evaluate our method on CASP13 and CASP14 targets. H-Packer is computationally efficient and shows favorable performance against conventional physics-based algorithms and is competitive against alternative deep learning solutions.Comment: Accepted as a conference paper at MLCB 2023. 8 pages main body, 20 pages with appendix. 10 figure

Screening of the novel antimicrobial drug, XF-73, against 2,527 Staphylococcus species clinical isolates

XF-73 (exeporfinium chloride) is a synthetic, di-cationic porphyrin derivative with rapid, potent bactericidal properties and a low propensity for engendering bacterial resistance. It is being developed clinically for the decolonization of Staphylococcus aureus in the nasal cavity to prevent post-operative staphylococcal infections. This study reports the minimum inhibitory concentration (MIC) of XF-73 in comparison to 22 antibiotics against a panel of >2,500 clinical isolates composed of 16 different Coagulase-positive and -negative Staphylococcus species from 33 countries. XF-73 was found to be effective against all isolates tested, with MICs ranging between ≤0.12 – 4 µg/ml (MIC50 and MIC90 values of 0.5 and 1 µg/ml respectively). XF-73 was found to be equally effective against antibiotic resistant isolates as antibiotic sensitive isolates, with no impact of pre-existing antibiotic resistance mechanisms to cell wall synthesis inhibitors (β-lactams, carbapenems, glycopeptides and cephalosporins), protein synthesis inhibitors (oxazolidinones, macrolides and tetracyclines), DNA synthesis inhibitors (fluoroquinolones) and a folate synthesis inhibitor. The panel selected also included examples of multidrug-resistant S. aureus isolates and, in all cases, the XF-73 MIC ranges were found to be similar against each of these groups. This dataset expands the knowledge of the breadth of activity of this novel antibacterial against a wide range of global S. aureus isolates and supports the potential utility of XF-73 for the treatment of patients who are S. aureus nasal carriers. Similar results were also obtained for multidrug-resistant isolates of other Staphylococcus species included in the study and collectively support the continued clinical development of XF-73 as an effective anti-staphylococcal drug

Dosimetric evaluation of heterogeneity corrections for RTOG 0236: stereotactic body radiotherapy of inoperable stage I-II non-small-cell lung cancer.

PURPOSE: Using a retrospective analysis of treatment plans submitted from multiple institutions accruing patients to the Radiation Therapy Oncology Group (RTOG) 0236 non-small-cell stereotactic body radiotherapy protocol, the present study determined the dose prescription and critical structure constraints for future stereotactic body radiotherapy lung protocols that mandate density-corrected dose calculations. METHOD AND MATERIALS: A subset of 20 patients from four institutions participating in the RTOG 0236 protocol and using superposition/convolution algorithms were compared. The RTOG 0236 protocol required a prescription dose of 60 Gy delivered in three fractions to cover 95% of the planning target volume. Additional requirements were specified for target dose heterogeneity and the dose to normal tissue/structures. The protocol required each site to plan the patient\u27s treatment using unit density, and another plan with the same monitor units and applying density corrections was also submitted. These plans were compared to determine the dose differences. Two-sided, paired Student\u27s t tests were used to evaluate these differences. RESULTS: With heterogeneity corrections applied, the planning target volume receiving \u3e/=60 Gy decreased, on average, 10.1% (standard error, 2.7%) from 95% (p = .001). The maximal dose to any point \u3e/=2 cm away from the planning target volume increased from 35.2 Gy (standard error, 1.7) to 38.5 Gy (standard error, 2.2). CONCLUSION: Statistically significant dose differences were found with the heterogeneity corrections. The information provided in the present study is being used to design future heterogeneity-corrected RTOG stereotactic body radiotherapy lung protocols to match the true dose delivered for RTOG 0236

Making Good Tenure Decisions

This article provides information on decision making on the granting or denial of tenure to a faculty member. It not only has an effect on the professional life of a colleague, it has a major influence on the direction and long-term quality of the department. The tenure decision in made in the sixth year of a tenure-track faculty appointment. If a faculty member has been on the tenure track at two institutions, the years of service at the first institution usually count toward those six years, unless the faculty member and his of her current institution agree in writing at the time of appointment that they will not or that only a certain number of them will. The sooner the person is terminated or helped to find another position, the better for him or her and for the department

Radio-Continuum study of the Nearby Sculptor Group Galaxies. Part 1: NGC 300 at lambda = 20 cm

A series of new radio-continuum (lambda=20 cm) mosaic images focused on the NGC 300 galactic system were produced using archived observational data from the VLA and/or ATCA. These new images are both very sensitive (rms=60 microJy) and feature high angular resolution (<10"). The most prominent new feature is the galaxy's extended radio-continuum emission, which does not match its optical appearance. Using these newly created images a number of previously unidentified discrete sources have been discovered. Furthermore, we demonstrate that a joint deconvolution approach to imaging this complete data-set is inferior when compared to an immerge approach.Comment: 13 pages, 12 figures, accepted to APSS, new version to correct the missing reference

Non-animal replacement methods for veterinary vaccine potency testing: state of the science and future directions

NICEATM and ICCVAM convened an international workshop to review the state of the science of human and veterinary vaccine potency and safety testing methods and to identify opportunities to advance new and improved methods that can further reduce, refine, and replace animal use. Six topics were addressed in detail by speakers and workshop participants and are reported in a series of six reports. This workshop report, the second in the series, provides recommendations for current and future use of nonanimal methods and strategies for veterinary vaccine potency testing. Workshop participants recommended that future efforts to replace animal use give priority to vaccines (1) that use large numbers of animals per test and for which many serials are produced annually, (2) that involve significant animal pain and distress during procedures, (3) for which the functional protective antigen has been identified, (4) that involve foreign animal/zoonotic organisms that are dangerous to humans, and (5) that involve pathogens that can be easily spread to wildlife populations. Vaccines identified as the highest priorities were those for rabies, Leptospira spp., Clostridium spp., Erysipelas, foreign animal diseases (FAD), poultry diseases, and fish diseases. Further research on the identification, purification, and characterization of vaccine protective antigens in veterinary vaccines was also identified as a priority. Workshop participants recommended priority research, development, and validation activities to address critical knowledge and data gaps, including opportunities to apply new science and technology. Recommendations included (1) investigations into the relative impact of various adjuvants on antigen quantification assays, (2) investigations into extraction methods that could be used for vaccines containing adjuvants that can interfere with antigen assays, and (3) review of the current status of rabies and tetanus human vaccine in vitro potency methods for their potential application to the corresponding veterinary vaccines. Workshop participants recommended enhanced international harmonization and cooperation and closer collaborations between human and veterinary researchers to expedite progress. Implementation of the workshop recommendations is expected to advance alternative in vitro methods for veterinary vaccine potency testing that will benefit animal welfare and replace animal use while ensuring continued protection of human and animal health