3D Convolutional Neural Networks for the diagnosis of 6 unique pathologies on head CT

Introduction: Head CT scans are a standard first-line tool used by physicians in the diagnosis of neurological pathologies. Recently, the development of deep learning models such as convolutional neural networks (CNNs) has allowed the rapid identification of bleeds and other pathologies on CT scans. This study aims to show that by training 3D CNNs with a larger, curated dataset, a more comprehensive list of potential diagnoses can be included in the detailed model. Methods: A retrospective study was performed using a dataset of 66,000 head CT studies from the Thomas Jefferson University health system. Studies were acquired using a natural language processor that searched for 60 different diagnoses, and the scans were then grouped into six distinct classes. Images were preprocessed by converting CT Hounsfield Units to greyscale, cropping to remove negative area, normalizing pixel values, and resizing to fit the input dimensions of the neural network. To automatically classify the studies, a three-dimensional residual neural network (3D-ResNet), was trained using 80% of the dataset as a training set and 20% of the dataset as a test set. Results: To achieve the most accurate results, a 3D-ResNet with 34 residual layers was used. Following the training of the 3D-RESNET, the model achieved an accuracy of 0.47 on the test set and 0.915 on the training set. Discussion: These results show a promising initial step toward machine-assisted diagnosis of head CT scans. As more potential diagnoses are added to models, the utility of the models increases, and more studies can be quickly processed. Going forward, neural networks could potentially be used to prioritize radiology worklists and perform automatic diagnosis of urgent scans

An Advertisement and Article Analysis of Skin Products and Topics in Popular Women’s Magazines: Implications for Skin Cancer Prevention

Background: In the United States, skin cancer is the most commonly diagnosed cancer, with an estimated 5 million people treated per year and annual medical treatment expenditures that exceed 8 billion dollars. The purpose of this study was two-fold: 1) to enumerate the number of advertisements for skin products with and without Sun Protection Factor (SPF) and to further analyze the specific advertisements for sunblock to determine if models, when present, depict sun safe behaviors and 2) to enumerate the number of articles related to the skin for content. Both aims include an assessment for differences in age and in magazines targeting a Black or Latina population. Methods: The sample for this cross sectional study was comprised of 99 issues of 14 popular United States magazines marketed to women, four of which market to a Black or Latina audience. Results: There were 6,142 advertisements, of which 1,215 (19.8%, 95% CI: 18.8-20.8%) were related to skin products. Among the skin product advertisements, 1,145 (93.8%, 95% CI: 93.9-96.3%) depicted skin products without SPF. The majority of skin articles (91.2%, 95% CI: 91.7-100.0%), skin product advertisements (89.9%, 95% CI: 88.2-91.6%), and sunblock advertisements featuring models (were found in magazines aimed at the older (\u3e24 yr) audience. Conclusion: Future research on this topic could focus on the extent to which images in these magazines translate into risky health behaviors, such as sun seeking, or excessive other harmful effects of UV radiation

Use of Pediatric Injectable Medicines Guidelines and Associated Medication Administration Errors: A Human Reliability Analysis

BACKGROUND: In a recent human reliability analysis (HRA) of simulated pediatric resuscitations, ineffective retrieval of preparation and administration instructions from online injectable medicines guidelines was a key factor contributing to medication administration errors (MAEs). OBJECTIVE: The aim of the present study was to use a specific HRA to understand where intravenous medicines guidelines are vulnerable to misinterpretation, focusing on deviations from expected practice (discrepancies) that contributed to large-magnitude and/or clinically significant MAEs. METHODS: Video recordings from the original study were reanalyzed to identify discrepancies in the steps required to find and extract information from the NHS Injectable Medicines Guide (IMG) website. These data were combined with MAE data from the same original study. RESULTS: In total, 44 discrepancies during use of the IMG were observed across 180 medication administrations. Of these discrepancies, 21 (48%) were associated with an MAE, 16 of which (36% of 44 discrepancies) made a major contribution to that error. There were more discrepancies (31 in total, 70%) during the steps required to access the correct drug webpage than there were in the steps required to read this information (13 in total, 30%). Discrepancies when using injectable medicines guidelines made a major contribution to 6 (27%) of 22 clinically significant and 4 (15%) of 27 large-magnitude MAEs. CONCLUSION AND RELEVANCE: Discrepancies during the use of an online injectable medicines guideline were often associated with subsequent MAEs, including those with potentially significant consequences. This highlights the need to test the usability of guidelines before clinical use

Oncogenic RAC1 and NRAS drive resistance to endoplasmic reticulum stress through MEK/ERK signalling.

Cancer cells are able to survive under conditions that cause endoplasmic reticulum stress (ER-stress), and can adapt to this stress by upregulating cell-survival signalling pathways and down-regulating apoptotic pathways. The cellular response to ER-stress is controlled by the unfolded protein response (UPR). Small Rho family GTPases are linked to many cell responses including cell growth and apoptosis. In this study, we investigate the function of small GTPases in cell survival under ER-stress. Using siRNA screening we identify that RAC1 promotes cell survival under ER-stress in cells with an oncogenic N92I RAC1 mutation. We uncover a novel connection between the UPR and N92I RAC1, whereby RAC1 attenuates phosphorylation of EIF2S1 under ER-stress and drives over-expression of ATF4 in basal conditions. Interestingly, the UPR connection does not drive resistance to ER-stress, as knockdown of ATF4 did not affect this. We further investigate cancer-associated kinase signalling pathways and show that RAC1 knockdown reduces the activity of AKT and ERK, and using a panel of clinically important kinase inhibitors, we uncover a role for MEK/ERK, but not AKT, in cell viability under ER-stress. A known major activator of ERK phosphorylation in cancer is oncogenic NRAS and we show that knockdown of NRAS in cells, which bear a Q61 NRAS mutation, sensitises to ER-stress. These findings highlight a novel mechanism for resistance to ER-stress through oncogenic activation of MEK/ERK signalling by small GTPases

Ultraviolet recall reaction after total body irradiation, etoposide, and methotrexate therapy.

Ultraviolet (UV) reactivation reactions are rare and can occur in areas of prior sunburn or UV light therapy after the administration of chemotherapy, antibiotics, and other medications. Reactions may occur within days, as described after methotrexate therapy, or may appear months later, as described with ampicillin. Such reactions have been variably termed UV recall, sunburn recall, photo recall, and photodermatitis reactivation, making classification difficult. We report a UV reactivation reaction in a patient with acute lymphocytic leukemia treated with total body irradiation, etoposide, and methotrexate. We propose the terms UV recall and UV enhancement be used in future reports to classify UV reactivation reactions in a scheme analogous to the terminology for cutaneous reactions after radiotherapy

Protein-peptide association kinetics beyond the seconds timescale from atomistic simulations

Understanding and control of structures and rates involved in protein-ligand binding are es- sential for drug design. Unfortunately, atomistic molecular dynamics (MD) simulations cannot di- rectly sample the excessively long residence and rearrangement times of tightly binding complexes. Here we exploit the recently developed multi-ensemble Markov model framework to compute full protein-peptide kinetics of the oncoprotein fragment 25−109Mdm2 and the nano-molar inhibitor peptide PMI. Using this system, we report, for the first time, direct estimates of kinetics beyond the seconds timescales using simulations of an all-atom MD model, with high accuracy and pre- cision. These results only require explicit simulations on the sub-milliseconds timescale and are tested against existing mutagenesis data and our own experimental measurements of the dissoci- ation and association rates. The full kinetic model reveals an overall downhill but rugged binding funnel with multiple pathways. The overall strong binding arises from a variety of conformations with different hydrophobic contact surfaces that interconvert on the milliseconds timescale.Funding is acknowledged by European Commission (ERC StG “pcCells” to F.N.), Deutsche Forschungsgemeinschaft (SFB 1114/C3, SFB 740/D7, and TRR 186/A12 to F.N. and SFB 1114/A4 to F.N. and T.W.). J.C. is a Wellcome Trust Senior Research Fellow (WT 095195MA). J.S. is a Marie Sklodowska-Curie Internationally outgoing fellow. M.D.C. is supported by a Biotechnology and Biological Sciences Research Council (BBSRC) studentship

Lymphocyte subpopulations in premature infants: An observational study

Background and objectives The infant's immune system evolves over the first months and years of life. Strong correlation exists between lymphocyte count, lymphocyte subpopulations and gestational age at birth. Associations with antenatal and postnatal steroid treatment, infection and chronic lung disease have also been described. Few published studies report the effect of increasing postnatal age (PNA) and comorbidities on lymphocyte subpopulations in premature infants beyond the first 4 months of life. This study aimed to describe changes in lymphocyte subpopulations in preterm infants up to 13 months PNA. Methods Premature infants (23–34 weeks completed gestation) from five centres had lymphocyte subpopulations measured at 2, 5 or 7, 12 and 13 months PNA alongside their vaccine responses in a vaccination trial. Results 393 blood samples from 151 babies were analysed. There was an increase in absolute numbers of total lymphocytes (median cell count 6.21×109/L at 13 months compared with 4.9×109/L at 2 months PNA) and CD3+, CD4+, CD8+, natural killer and B cells with increasing age. At 2 months PNA, there was a positive correlation between gestation and CD3+ and CD4+ counts (r=0.32 and 0.46, respectively) and proportions (r=0.22 and 0.41, respectively), and CD4+:CD8+ ratios (r=0.57), but a negative correlation with CD8+ proportions (r=−0.32). Conclusions This longitudinal study describes the distribution of lymphocyte subpopulations in premature infants and provides reference ranges for the major lymphocyte subsets to help guide clinicians when assessing premature infants for immunodeficiency in the first year of life. Trial registration number EudraCT 2007-007535-23

Genotypic characterization of Streptococcus pneumoniae serotype 19F in Malaysia

Streptococcus pneumoniae is an epidemiologically important bacterial pathogen. Recently, we reported the antibiotic susceptibility patterns of a limited collection of pneumococcal isolates in Malaysia with a high prevalence of erythromycin resistant strains. In the present study, 55 of the pneumococcal isolates of serotype 19F were further analysed by pulsed field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). The generated genotypic patterns were then correlated with the antibiograms previously reported. Forty-seven different PFGE profiles (PTs) were obtained, showing that the isolates were genetically diverse. MLST identified 16 sequence types (STs) with ST-236 being predominant (58.2%), followed by ST-81 (10.3%). Among the ST-236 isolates, 22 were erythromycin resistant S. pneumoniae (ERSP) and 15 were trimethoprim/sulfamethoxazole (TMP/SMX) resistant, while among ST-81, four isolates were ERSP and two were TMP/SMX resistant. The high prevalence of erythromycin resistant serotype 19F isolates of ST-236 in this study has also been reported in other North and South East Asian countries