Non-Thermal Solar Wind Electron Velocity Distribution Function.

The quiet-time solar wind electrons feature non-thermal characteristics when viewed from the perspective of their velocity distribution functions. They typically have an appearance of being composed of a denser thermal "core" population plus a tenuous energetic "halo" population. At first, such a feature was empirically fitted with the kappa velocity space distribution function, but ever since the ground-breaking work by Tsallis, the space physics community has embraced the potential implication of the kappa distribution as reflecting the non-extensive nature of the space plasma. From the viewpoint of microscopic plasma theory, the formation of the non-thermal electron velocity distribution function can be interpreted in terms of the plasma being in a state of turbulent quasi-equilibrium. Such a finding brings forth the possible existence of a profound inter-relationship between the non-extensive statistical state and the turbulent quasi-equilibrium state. The present paper further develops the idea of solar wind electrons being in the turbulent equilibrium, but, unlike the previous model, which involves the electrostatic turbulence near the plasma oscillation frequency (i.e., Langmuir turbulence), the present paper considers the impact of transverse electromagnetic turbulence, particularly, the turbulence in the whistler-mode frequency range. It is found that the coupling of spontaneously emitted thermal fluctuations and the background turbulence leads to the formation of a non-thermal electron velocity distribution function of the type observed in the solar wind during quiet times. This demonstrates that the whistler-range turbulence represents an alternative mechanism for producing the kappa-like non-thermal distribution, especially close to the Sun and in the near-Earth space environment.

Gut barrier-microbiota imbalances in early life lead to higher sensitivity to inflammation in a murine model of C-section delivery.

BACKGROUND: Most interactions between the host and its microbiota occur at the gut barrier, and primary colonizers are essential in the gut barrier maturation in the early life. The mother-offspring transmission of microorganisms is the most important factor influencing microbial colonization in mammals, and C-section delivery (CSD) is an important disruptive factor of this transfer. Recently, the deregulation of symbiotic host-microbe interactions in early life has been shown to alter the maturation of the immune system, predisposing the host to gut barrier dysfunction and inflammation. The main goal of this study is to decipher the role of the early-life gut microbiota-barrier alterations and its links with later-life risks of intestinal inflammation in a murine model of CSD. RESULTS: The higher sensitivity to chemically induced inflammation in CSD mice is related to excessive exposure to a too diverse microbiota too early in life. This early microbial stimulus has short-term consequences on the host homeostasis. It switches the pup's immune response to an inflammatory context and alters the epithelium structure and the mucus-producing cells, disrupting gut homeostasis. This presence of a too diverse microbiota in the very early life involves a disproportionate short-chain fatty acids ratio and an excessive antigen exposure across the vulnerable gut barrier in the first days of life, before the gut closure. Besides, as shown by microbiota transfer experiments, the microbiota is causal in the high sensitivity of CSD mice to chemical-induced colitis and in most of the phenotypical parameters found altered in early life. Finally, supplementation with lactobacilli, the main bacterial group impacted by CSD in mice, reverts the higher sensitivity to inflammation in ex-germ-free mice colonized by CSD pups' microbiota. CONCLUSIONS: Early-life gut microbiota-host crosstalk alterations related to CSD could be the linchpin behind the phenotypic effects that lead to increased susceptibility to an induced inflammation later in life in mice. Video Abstract.

Developing an Artificial Intelligence-Based Representation of a Virtual Patient Model for Real-Time Diagnosis of Acute Respiratory Distress Syndrome.

Acute Respiratory Distress Syndrome (ARDS) is a condition that endangers the lives of many Intensive Care Unit patients through gradual reduction of lung function. Due to its heterogeneity, this condition has been difficult to diagnose and treat, although it has been the subject of continuous research, leading to the development of several tools for modeling disease progression on the one hand, and guidelines for diagnosis on the other, mainly the "Berlin Definition". This paper describes the development of a deep learning-based surrogate model of one such tool for modeling ARDS onset in a virtual patient: the Nottingham Physiology Simulator. The model-development process takes advantage of current machine learning and data-analysis techniques, as well as efficient hyperparameter-tuning methods, within a high-performance computing-enabled data science platform. The lightweight models developed through this process present comparable accuracy to the original simulator (per-parameter R2 > 0.90). The experimental process described herein serves as a proof of concept for the rapid development and dissemination of specialised diagnosis support systems based on pre-existing generalised mechanistic models, making use of supercomputing infrastructure for the development and testing processes and supported by open-source software for streamlined implementation in clinical routines.

A Case for Electron-Astrophysics.

The smallest characteristic scales, at which electron dynamics determines the plasma behaviour, are the next frontier in space and astrophysical plasma research. The analysis of astrophysical processes at these scales lies at the heart of the research theme of electron-astrophysics. Electron scales are the ultimate bottleneck for dissipation of plasma turbulence, which is a fundamental process not understood in the electron-kinetic regime. In addition, plasma electrons often play an important role for the spatial transfer of thermal energy due to the high heat flux associated with their velocity distribution. The regulation of this electron heat flux is likewise not understood. By focussing on these and other fundamental electron processes, the research theme of electron-astrophysics links outstanding science questions of great importance to the fields of space physics, astrophysics, and laboratory plasma physics. In this White Paper, submitted to ESA in response to the Voyage 2050 call, we review a selection of these outstanding questions, discuss their importance, and present a roadmap for answering them through novel space-mission concepts.

Electron Energy Partition across Interplanetary Shocks. I. Methodology and Data Product.

Analyses of 15,314 electron velocity distribution functions (VDFs) within ±2 hr of 52 interplanetary (IP) shocks observed by the Wind spacecraft near 1 au are introduced. The electron VDFs are fit to the sum of three model functions for the cold dense core, hot tenuous halo, and field-aligned beam/strahl component. The best results were found by modeling the core as either a bi-kappa or a symmetric (or asymmetric) bi-self-similar VDF, while both the halo and beam/strahl components were best fit to bi-kappa VDF. This is the first statistical study to show that the core electron distribution is better fit to a self-similar VDF than a bi-Maxwellian under all conditions. The self-similar distribution deviation from a Maxwellian is a measure of inelasticity in particle scattering from waves and/or turbulence. The ranges of values defined by the lower and upper quartiles for the kappa exponents are κ ec ~ 5.40-10.2 for the core, κ eh ~ 3.58-5.34 for the halo, and κ eb ~ 3.40-5.16 for the beam/strahl. The lower-to-upper quartile range of symmetric bi-self-similar core exponents is s ec ~ 2.00-2.04, and those of asymmetric bi-self-similar core exponents are p ec ~ 2.20-4.00 for the parallel exponent and q ec ~ 2.00-2.46 for the perpendicular exponent. The nuanced details of the fit procedure and description of resulting data product are also presented. The statistics and detailed analysis of the results are presented in Paper II and Paper III of this three-part study.

Spin in articles about minimally invasive transanal total mesorectal excision: an assessment of the current literature.

AIM: Minimally invasive transanal total mesorectal excision (TaTME) is a new approach for treating rectal cancer. 'Spin' can be defined as 'reporting strategies to highlight that the experimental treatment is beneficial' despite limitations in study design. The aim of this study was to assess spin within publications about TaTME. METHOD: EMBASE and MEDLINE (2009-2017) were searched for publications assessing TaTME in rectal cancer. All papers published between 2009 and 2017 were eligible for inclusion. Study titles and abstracts were assessed for evidence of spin, as previously defined. RESULTS: A total of 1202 studies were identified through our search, and 73 were included. The majority were case series (n = 48, 66%). A total of 55 publications (75%) had evidence of spin within at least one domain. The most common type of spin was claiming safety without describing how this was defined or tested (56%). Other strategies included claiming superiority without support (33%) and reporting nonsignificance as equivalence (42%). We did not find that year of publication (P = 0.61), study design (P = 0.60), number of patients (P = 0.85) or declared conflict of interest (P = 0.43) were associated with spin. CONCLUSION: We have shown that spin is common within studies assessing TaTME for rectal cancer. Despite a lack of support from study results, in the majority of studies authors concluded that TaTME is safe for use in rectal cancer. Readers of study abstracts describing new techniques need to be cautious about accepting the authors' conclusions, especially in case series and observational studies.

Operative vectors, anatomic distortion, fluid dynamics and the inherent effects of pneumatic insufflation encountered during transanal total mesorectal excision.

BACKGROUND: Transanal total mesorectal excision (taTME) is an altogether different approach to rectal cancer surgery, and the effects of carbon dioxide (CO2) on this dissection remain poorly described. METHODS: This article critically examines the effect of carbon dioxide insufflation and the workspace it creates during the process of taTME. The unique aspects of insulation with this approach are governed by the laws of physics, especially the principles of fluid dynamics, an area that remains poorly described for laparoscopy and not at all described for taTME. RESULTS: A summary of established factors which affect the operative field of the taTME surgeon is delineated and further explored. In addition, new concepts regarding gas delivery, such as insufflation vectors, anatomic distortion, hyper-dissection, and workspace volume rate of change as a function of taTME dissection time, are addressed. Collectively, these factors pose important challenges which increase case complexity and are thus essential for taTME trainers and trainees alike to understand. CONCLUSIONS: Although an invisible gas, CO2 insufflation with taTME produces markedly visible effects which are imposed upon the operative field. This can result in anatomic distortion and misperception of operative planes. Thus, practicing taTME surgeons should be cognizant of these effects.

The evaluation of the relevance of thrombin generation and procoagulant activity in thrombotic risk assessment in BCR-ABL-negative myeloproliferative neoplasm patients.

INTRODUCTION: It has been recently suggested that microparticles (MP) play a role in the pathogenesis of thrombotic complications. This study aimed to assess the contribution of procoagulant activity expressed by circulating MP in thrombotic events in MPN patients. METHODS: Seventy-four MPN patients were enrolled in a trans-sectional study. The MP procoagulant activity was measured using two assays: (i) the thrombin generation (TG) assay used in different conditions with the addition of both tissue factor (TF) and phospholipids (PL) and with the addition of TF or PL alone and (ii) the PROCOAG-PPL assay. RESULTS: The mean age was 62 (26 men and 48 women). The prevalence of thrombotic events was 28%. When comparing patients with thrombosis to those without, age, sex, MPN type, cardiovascular risk factors, and history of thrombosis were not significantly associated with thrombosis. The JAK2 V617F mutation was significantly associated with thrombotic events (90% vs 67%; P=.04). Results from the TG assay and the PROCOAG-PPL assays did not demonstrate a significant association between the MP procoagulant activity and thrombotic events. CONCLUSION: The MP procoagulant activity did not predict thrombosis in MPN patients. The contribution of TG assay in the assessment of the thrombotic risk is still in debate.

Prophylactic mesh to prevent parastomal hernia: a meta-analysis of randomized controlled studies.

The aim of the present meta-analysis was to determine whether prophylactic mesh decreases the odds of parastomal hernia formation. Randomized controlled trials referenced in MEDLINE or EMBASE between 1946 and 2016 comparing prophylactic mesh to standard stoma formation were included. The primary outcome was occurrence of parastomal hernia. Secondary outcomes were parastomal hernia requiring surgical intervention and complications. Odds ratios were calculated for the primary and secondary outcomes. Subgroup analyses were conducted based on mesh type, mesh location, laparoscopic versus open, and method of hernia diagnosis. Nine randomized controlled trials with 569 participants were included. There was a significant decrease in the odds of developing a parastomal hernia in the prophylactic mesh group [odds ratio (OR) 0.21, 95% confidence interval (CI) 0.11-0.38, p < 0.00001, I 2 = 36%], as well as decreased odds of requiring surgical repair (OR 0.36, 95% CI 0.15-0.87, p = 0.02, I 2 = 0%). There was no evidence that prophylactic mesh increased the odds of surgical complications (seven studies, OR 1.34, 95% CI 0.73-2.46, p = 0.34, I 2 = 34%) or stoma-specific complications (eight studies, OR 0.65, 95% CI 0.40-1.05, p = 0.08, I 2 = 0%). There was a subgroup effect with synthetic mesh associated with a lower incidence of parastomal hernias which was not appreciated in the biologic mesh group (test of subgroup effect p = 0.01). Five studies had a high risk of bias. The Grades of Recommendation, Assessment, Development and Evaluation quality of evidence was moderate. Prophylactic mesh is associated with decreased odds of parastomal hernia formation and the need for surgical repair. There is no evidence that mesh placement increases the odds of complications.

Impact of surgeon laparoscopic training and case volume of laparoscopic surgery on conversion during elective laparoscopic colorectal surgery.

AIM: The study aimed to determine whether laparoscopic volume and type of training influence conversion during elective laparoscopic colorectal surgery. METHOD: An Institutional Review Board-approved prospective database was reviewed for patients who underwent colorectal resection, performed by six colorectal surgeons, for all diagnoses from 2009 to 2014. Surgeons were designated as laparoscopic- or open-trained based on formal laparoscopic colorectal surgery training, and were classified as low laparoscopic volume (LLV) (i.e. had performed < 100 laparoscopic procedures) or high laparoscopic volume (HLV) (i.e. had performed ≥ 100 laparoscopic procedures). Technique was laparoscopic, open or converted (pre-emptive or reactive). Conversion was compared among three groups: LLV, laparoscopic trained (group A); LLV, open trained (group B); and HLV, open trained (group C). RESULTS: In total, 159/567 procedures were open and 408 laparoscopic procedures were attempted. Of the 408 laparoscopic procedures, 73 were converted. Among the 567 patients [mean age: 56 ± 17 years (44% male)], the overall conversion rate was 13% (73/567), including 75% pre-emptive and 25% reactive. Conversion rates for groups A, B and C were 17.9%, 42.6% and 14.3%, respectively. Significantly higher conversion was seen in group B compared with group C (P = 0.01), but not between group A and group C (P = 0.85) or between group B and group A (P = 0.11). Converted patients were older (P < 0.001), with lower rates of proctectomy (P = 0.007), higher rates of anastomosis (P < 0.001) and higher body mass index (BMI) (P < 0.001). After adjusting for patient and surgeon factors, training type was not associated with conversion (P = 0.15). Compared with successful laparoscopy, converted patients had a significantly higher incidence of ileus (P < 0.001), length of stay (P = 0.002), time to flatus (OR = 3.21, P < 0.001) and time to solids (P < 0.001). Converted patients experienced increased morbidity. CONCLUSION: Training is not associated with conversion. Rather, HLV surgeons, regardless of training, convert less frequently than do LLV surgeons.

Sacral neuromodulation for the treatment of faecal incontinence following proctectomy.

AIM: This study assessed the effectiveness of sacral neuromodulation (SNM) for faecal incontinence (FI) following proctectomy with colorectal or coloanal anastomosis. METHODS: An Institutional Review Board (IRB)-approved database identified patients treated for FI following proctectomy (SNM-P) for benign or malignant disease, who were matched 1:1 according to preoperative Cleveland Clinic Florida Faecal Incontinence Scores (CCF-FIS) with patients without proctectomy (SNM-NP). Primary outcome was change in CCF-FIS. RESULTS: Twelve patients (seven women) were in the SNM-P group and 12 (all women) were in the SNM-NP group. In the SNM-P group, six patients underwent proctectomy for low rectal cancer and five received neoadjuvant chemoradiation. Five patients had handsewn anastomosis, and one had stapled coloanal anastomosis. One lead explantation occurred after a failed 2-week SNM percutaneous trial. Six patients underwent proctectomy for benign conditions. Within-group analyses revealed significant improvement in CCF-FIS in the SNM-P group (reduction from a score of 18 to a score of 14; P = 0.02), which was more profound for benign disease (reduction from 14.5 to 8.5) than for rectal cancer (reduction from 19.5 to 15). SNM was explanted in 66% and 33% of patients after proctectomy for malignant and benign conditions, respectively. In the SNM-NP group, 41% underwent overlapping sphincteroplasty. One patient received chemoradiation for anal cancer. Within-group analysis for the SNM-NP group showed significant improvement in CCF-FIS (a reduction from 17.5 to 4.0; P = 0.003). There was significant improvement in CCF-FIS in patients without previous proctectomy (mean delta CCF-FIS: 11.1 vs 4.7; P = 0.011). Analysis of covariance (ANCOVA) reaffirmed that controls outperformed proctectomy patients (P = 0.006). CONCLUSION: SNM for FI after proctectomy appears less effective than SNM in patients without proctectomy, with high device explantation rates, particularly after neoadjuvant chemoradiation and proctectomy for low rectal cancer.

Faecal incontinence in patients with a sphincter defect: comparison of sphincteroplasty and sacral nerve stimulation.

AIM: Sphincteroplasty (SP) is used to treat faecal incontinence (FI) in patients with a sphincter defect. Although sacral nerve stimulation (SNS) is used in patients, its outcome in patients with a sphincter defect has not been definitively evaluated. We compared the results of SP and SNS for FI associated with a sphincter defect. METHOD: Patients treated by SNS or SP for FI with an associated sphincter defect were retrospectively identified from an Institutional Review Board approved prospective database. Patients with ultrasound evidence of a sphincter defect were matched by age, gender and body mass index. The main outcome measure was change in the Cleveland Clinic Florida Faecal Incontinence Score (CCF-FIS). RESULTS: Twenty-six female patients with a sphincter defect were included in the study. The 13 patients in each group were similar for age, body mass index, initial CCF-FIS and the duration of follow-up. No differences were observed in parity (P = 1.00), the rate of concomitant urinary incontinence (P = 0.62) or early postoperative complications. Within-group analysis showed a significant reduction of the CCF-FIS among patients having SNS (15.9-8.4; P = 0.003) but not SP (16.9-12.9; P = 0.078). There was a trend towards a more significant improvement in CCF-FIS in the SNS than in the SP group (post-treatment CCF-FIS 8.4 vs 12.9, P = 0.06). Net improvement in CCF-FIS was not significantly different between the groups (P = 0.06). CONCLUSION: Significant improvement in CCF-FIS was observed in patients treated with SNS but not SP patients. A trend towards better results was seen with SNS.

Differences during the first lactation between cows cloned by somatic cell nuclear transfer and noncloned cows.

Lactation performance is dependent on both the genetic characteristics and the environmental conditions surrounding lactating cows. However, individual variations can still be observed within a given breed under similar environmental conditions. The role of the environment between birth and lactation could be better appreciated in cloned cows, which are presumed to be genetically identical, but differences in lactation performance between cloned and noncloned cows first need to be clearly evaluated. Conflicting results have been described in the literature, so our aim was to clarify this situation. Nine cloned Prim' Holstein cows were produced by the transfer of nuclei from a single fibroblast cell line after cell fusion with enucleated oocytes. The cloned cows and 9 noncloned counterparts were raised under similar conditions. Milk production and composition were recorded monthly from calving until 200d in milk. At 67d in milk, biopsies were sampled from the rear quarter of the udder, their mammary epithelial cell content was evaluated, and mammary cell renewal, RNA, and DNA were then analyzed in relevant samples. The results showed that milk production did not differ significantly between cloned and noncloned cows, but milk protein and fat contents were less variable in cloned cows. Furthermore, milk fat yield and contents were lower in cloned cows during early lactation. At around 67 DIM, milk fat and protein yields, as well as milk fat, protein, and lactose contents, were also lower in cloned cows. These lower yields could be linked to the higher apoptotic rate observed in cloned cows. Apoptosis is triggered by insulin-like factor growth binding protein 5 (IGFBP5) and plasminogen activator inhibitor (PAI), which both interact with CSN1S2. During our experiments, CSN1S2 transcript levels were lower in the mammary gland of cloned cows. The mammary cell apoptotic rate observed in cloned cows may have been related to the higher levels of DNA (cytosine-5-)-methyltransferase 1 (DNMT1) transcripts, coding for products that maintain the epigenetic status of cells. We conclude, therefore, that milk production in cloned cows differs slightly from that of noncloned cows. These differences may be due, in part, to a higher incidence of subclinical mastitis. They were associated with differences in cell apoptosis and linked to variations in DNMT1 mRNA. However, milk protein and fat contents were more similar among cloned cows than among noncloned cows.

Survival following salvage abdominoperineal resection for persistent and recurrent squamous cell carcinoma of the anus: do these disease categories affect survival?

AIM: This study aimed to investigate the results of salvage abdominoperineal excision (APR) in patients with persistent or recurrent squamous cell carcinoma of the anus (SCCA). METHOD: Patients with anal neoplasia were identified from a prospective database. Patients with invasive SCCA with demonstrated failure of chemoradiation therapy (CRT) who underwent salvage APR for one of three disease categories (persistent, < 6 months post-CRT; early recurrent, 6-24 months post-CRT; late recurrent, > 24 months post-CRT) were included. The primary outcome was overall survival after salvage APR. Tumour size, metastatic lymph nodes (LN), circumferential resection margin positivity (CRM) and neurolymphovascular invasion (NLVI) were correlated with the outcome. RESULTS: Thirty-six patients with a median 3-year overall survival of 46% (median follow-up 24 months) underwent salvage APR due to persistent or recurrent SCCA (14 men, mean age 59 years). Eleven (31%) patients were diagnosed with persistent disease, 17 (47%) with early and 8 (22%) with late recurrence. Two-year overall survival of Stage 0/I/II and III/IV disease was 81.5% and 33.74%, respectively (P = 0.022). Overall disease stage was associated with disease categorization (P = 0.009): patients with persistent disease or early recurrence had a significantly higher disease stage than patients with late recurrence (OR = 20.9 and 17.2). Despite apparently improved survival in patients with late disease recurrence on live table analysis, no significant difference was identified in overall survival when stratified by disease category on log-rank test analysis. CONCLUSION: Persistent and recurrent disease does not show any significant difference in survival, but patients with late recurrence may have a better prognosis.

Summer 2006 war on Lebanon: a lesson in community resilience.

The internally displaced persons (IDPs) during the July 2006 war in Lebanon exhibited a high level of community resilience, affirmed by relief agencies and public health professionals. Data from personal observations, interviews, meetings and published material were used to examine factors contributing to this resilience. Findings suggested that community resilience is a process rather than an outcome. The sense of a collective identity, prior experience with wars and social support networks have contributed to building up IDP's resilience over time, while community cohesiveness, adequate public health interventions, social solidarity and a connected political leadership helped to sustain it during and shortly after the war. This paper examines implications for public health professionals and argues for a paradigm shift in disaster relief practice.

Which PrP haplotypes in a French sheep population are the most susceptible to atypical scrapie?

A French sheep case control study has been organised to estimate the effects of the PrP haplotypes on resistance to atypical scrapie. The ALHQ and AFRQ haplotypes are significantly more susceptible than the others.