Identifying predictive features of autism spectrum disorders in a clinical sample of adolescents and adults using machine learning

Diagnosing autism spectrum disorders (ASD) is a complicated, time-consuming process which is particularly challenging in older individuals. One of the most widely used behavioral diagnostic tools is the Autism Diagnostic Observation Schedule (ADOS). Previous work using machine learning techniques suggested that ASD detection in children can be achieved with substantially fewer items than the original ADOS. Here, we expand on this work with a specific focus on adolescents and adults as assessed with the ADOS Module 4. We used a machine learning algorithm (support vector machine) to examine whether ASD detection can be improved by identifying a subset of behavioral features from the ADOS Module 4 in a routine clinical sample of N = 673 high-functioning adolescents and adults with ASD (n = 385) and individuals with suspected ASD but other best-estimate or no psychiatric diagnoses (n = 288). We identified reduced subsets of 5 behavioral features for the whole sample as well as age subgroups (adolescents vs. adults) that showed good specificity and sensitivity and reached performance close to that of the existing ADOS algorithm and the full ADOS, with no significant differences in overall performance. These results may help to improve the complicated diagnostic process of ASD by encouraging future efforts to develop novel diagnostic instruments for ASD detection based on the identified constructs as well as aiding clinicians in the difficult question of differential diagnosis

Choosing the Right Treatment Option for the Right R/M HNSCC Patient: Should We Adhere to PFE for First-Line Therapy?

Background: The landmark EXTREME trial established cisplatin, 5-fluorouracil and cetuximab (PFE) as first-line chemotherapy (1L-ChT) for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). We were interested in outcome differences of R/M HNSCC in 1L-ChT and factors influencing outcome in certain subgroups, especially patients receiving PFE, and the value of PFE compared to other 1L-ChT regimens to provide real world evidence (RWE). Methods: For this retrospective monocentric study, 124 R/M HNSCC patients without curative surgical or radiotherapy options receiving at least one cycle of 1L-ChT were eligible. We analyzed their outcome using Kaplan-Meier plot and Cox regression to identify predictors for prolonged survival. Results: Subgroups benefiting significantly from PFE were patients suffering from an index HNSCC outside the oropharynx. The PFE regimen proved to be superior to all other 1L-ChT regimens in clinical routine. Significant outcome differences between PFE treatment within or outside controlled trials were not seen. Conclusion: This retrospective analysis provides RWE for factors linked to improved outcome. Subgroup analyses highlight the lasting value of PFE among the growing spectrum of 1L-ChT. Importantly, fit smokers with high level alcohol consumption benefit from PFE; considering the patient’s lifestyle factors, PFE should not be ignored in decision-making

Functional organization of a single nif

The mesophilic methanogenic archaeon Methanosarcina mazei strain Gö1 is able to utilize molecular nitrogen (N2) as its sole nitrogen source. We have identified and characterized a single nitrogen fixation (nif) gene cluster in M. mazei Gö1 with an approximate length of 9 kbp. Sequence analysis revealed seven genes with sequence similarities to nifH, nifI1, nifI2, nifD, nifK, nifE and nifN, similar to other diazotrophic methanogens and certain bacteria such as Clostridium acetobutylicum, with the two glnB-like genes (nifI1 and nifI2) located between nifH and nifD. Phylogenetic analysis of deduced amino acid sequences for the nitrogenase structural genes of M. mazei Gö1 showed that they are most closely related to Methanosarcina barkeri nif2 genes, and also closely resemble those for the corresponding nif products of the gram-positive bacterium C. acetobutylicum. Northern blot analysis and reverse transcription PCR analysis demonstrated that the M. mazei nif genes constitute an operon transcribed only under nitrogen starvation as a single 8 kb transcript. Sequence analysis revealed a palindromic sequence at the transcriptional start site in front of the M. mazei nifH gene, which may have a function in transcriptional regulation of the nif operon

Sustainable reduction of antibiotic-induced antimicrobial resistance (ARena) in German ambulatory care: study protocol of a cluster randomised trial

Background: Despite many initiatives to enhance the rational use of antibiotics, there remains substantial room for improvement. The overall aim of this study is to optimise the appropriate use of antibiotics in German ambulatory care in patients with acute non-complicated infections (respiratory tract infections, such as bronchitis, sinusitis, tonsillitis and otitis media), community-acquired pneumonia and non-complicated cystitis, in order to counter the advancing antimicrobial resistance development. Methods: A three-armed cluster randomised trial will be conducted in 14 practice networks in two German federal states (Bavaria and North Rhine-Westphalia) and an added cohort that reflects standard care. The trial is accompanied by a process evaluation. Each arm will receive a different set of implementation strategies. Arm A receives a standard set, comprising of e-learning on communication with patients and quality circles with data-based feedback for physicians, information campaigns for the public, patient information material and performance-based additional reimbursement. Arm B receives this standard set plus e-learning on communication with patients and quality circles with data-based feedback tailored for non-physician health professionals of the practice team and information material for tablet computers (culture sensitive). Arm C receives the standard set as well as a computerised decision support system and quality circles in local multidisciplinary groups. The study aims to recruit 193 practices which will provide data on 23,934 patients each year (47,867 patients in total). The outcome evaluation is based on claims data and refers to established indicators of the European Surveillance of Antimicrobial Consumption Network (ESAC-Net). Primary and secondary outcomes relate to prescribing of antibiotics, which will be analysed in multivariate regression models. The process evaluation is based on interviews with surveys among physicians, non-physician health professionals of the practice team and stakeholders. A patient survey is conducted in one of the study arms. Interview data will be qualitatively analysed using thematic framework analysis. Survey data of physicians, non-physician health professionals of the practice team and patients will use descriptive and exploratory statistics for analysis. Discussion: The ARena trial will examine the effectiveness of large scale implementation strategies and explore their delivery in routine practice. Trial registration: ISRCTN, ISRCTN58150046 . Registered 24 August 2017

Incidence and survival of HNSCC patients living with HIV compared with HIV-negative HNSCC patients

Purpose: The aim was to analyze the incidence and survival of patients living with HIV (PLWH) with head and neck squamous cell carcinoma (HNSCC) and to compare with a control group of HIV-negative HNSCC patients. Methods: Clinicopathological data and predictors for overall survival (OS) and disease-free survival (DFS) were investigated (2009-2019). Results: 50 of 5151 HNSCC patients (0.97%) were PLWH, and 76% were smokers. Age <= 60 years, HIV-PCR <= 50 copies, CD4 cells <= 200/mm(3), cART treatment, T and UICC classification, oral cavity and nasal/paranasal sinuses, and therapy were significantly associated with OS in univariate analysis. In the multivariate analysis, only age and HIV-PCR independently predicted OS. The OS of the 50 PLWH was not significantly altered compared with the 5101 HIV-negative controls. However, OS and DFS were significantly inferior in advanced tumor stages of PLWH compared with an age-matched control group of 150 HIV-negative patients. Conclusions: PLWH were diagnosed with HNSCC at a significantly younger age compared to HIV-negative patients. Taking into account patient age at initial diagnosis, both OS and DFS rates in PLWH are significantly worse compared with a matched control group of HIV-negative patients in advanced tumor stages UICC III/IV. The prognosis (OS) is improved when taking cART treatment, the HIV viral load is undetectable and CD4 count is high

Antigen-Specific versus Non-Antigen-Specific Immunoadsorption in ABO-Incompatible Renal Transplantation

Introduction: ABO-incompatible (ABOi) renal transplantation (RTx) from living donors is an established procedure to expand the donor pool for patients with end stage renal disease. Immunoadsorption (IA) is a standard procedure for the removal of preformed antibodies against the allograft. In this study, antigen-specific and non-antigen-specific IA in ABOi RTx were compared. Patients and Methods: 10 patients underwent antigen-specific IA (Glycosorb group) and 13 patients non-antigen-specific IA (Immunosorba group). The effects of both procedures regarding antibody reduction, number of treatments, complications, costs, as well as the allograft function and patient survival were compared between both groups. Results: Although the IgG levels were reduced equally by both procedures (p=0.82), the reduction of the IgM level was more effective in the Glycosorb group (p=0.0172). Patients in both groups required a median number of 6 IA before ABOi RTx. Allograft function at one year after AB0i RTx was similar in both groups (estimated glomerular filtration rate: 66 vs. 64 ml/min/1.73m² respectively), with a death-censored graft survival of 90.0% and 92.3% respectively. Complication rates did not differ between procedures. Due to the reuse of non-antigen-specific Immunosorba columns, costs were considerably lower in this group; however, the use of the Immunosorba-based IA was less time-efficient. Conclusion: Considering upcoming alternatives as simultaneous performance of dialysis and IA or a possible reuse of Glycosorb columns, this might become less relevant in the future