The effect of Zostera noltei recolonization on the sediment mercury vertical profiles of a recovering coastal lagoon.

Mercury's extreme toxicity and persistence in the environment justifies a thorough evaluation of its dynamics in ecosystems. Aveiro Lagoon (Portugal) was for decades subject to mercury effluent discharges. A Nature-based Solution (NbS) involving Zostera noltei re-colonization is being tested as an active ecosystem restoration measure. To study the effect of Zostera noltei on the sediment contaminant biogeochemistry, seasonal (summer/winter) sediment, interstitial water and labile mercury vertical profiles were made in vegetated (Transplanted and Natural seagrass meadows) and non-vegetated sites (Bare-bottom area). While no significant differences (p > 0.05) were observed in the sedimentary phase, Zostera noltei presence reduced the reactive/labile mercury concentrations in the top sediment layers by up to 40% when compared to non-vegetated sediment, regardless of season. No differences were found between vegetated meadows, highlighting the fast recovery of the contaminant regulation ecosystem function provided by the plants after re-colonization and its potential for the rehabilitation of historically contaminated ecosystems.

Zostera noltei response to transplantation into historically Hg-contaminated sediments (A mesocosm experiment): Growth, bioaccumulation and photosynthetic performance.

The present study aimed to evaluate the effectiveness of seagrass recolonization as a nature-based solution for the recovery of a coastal area historically contaminated by mercury (Laranjo Bay, Ria de Aveiro, Portugal). A mesocosm approach was employed to assess the resistance of Zostera noltei to transplantation into contaminated sediments collected in-situ (0.5-20 mg kg-1 Hg). At each sampling time (15, 30, 60, 120 and 210 days), the resistance of transplanted Z. noltei was evaluated through growth parameters (biomass and coverage area), photosynthetic performance and elemental composition. Although some significant differences (p ≤ 0.05) were observed between treatments, essentially associated with the elemental composition of plant tissues, the most relevant variations were associated with seasonality. Overall, plants were found to not be affected by sediment contamination, under the tested concentrations, suggesting that recolonization with Z. noltei can be an effective restoration strategy for historically contaminated coastal areas.

Metal(oid)s accumulation (Hg and As) and their biochemical effects in Halimione portulacoides (Ria de Aveiro, Portugal).

For decades, mercury (Hg) and arsenic (As) were discharged into the Aveiro Lagoon. This study was designed to assess the natural attenuation process evolution by: (1) evaluating Hg and As concentration in sediments and in Halimione portulacoides, and assess the long-term evolution of a historically contaminated salt-marsh system; (2) evaluating the stress levels imposed by Hg and As, and the mechanisms triggered to squash oxidative damage. Concentrations of Hg and As in sediments varied considerably between sampling locations. H. portulacoides did not bioconcentrate Hg and As, restricted translocation to aerial biomass and immobilized contaminants in cell walls. The ions that reached the cytosol induced oxidative stress, restrained by antioxidant mechanisms, especially SOD and CAT activity. Results show that after 25 years of natural attenuation, contamination decreased in the sediment, but remains above non-contaminated systems and continues to induce toxicity in the saltmarsh halophyte community, evidencing the persistent effect of Hg and As contamination.

Mercury bioaccessibility in fish and seafood: Effect of method, cooking and trophic level on consumption risk assessment.

The bioaccessible Hg fraction in fish and seafood commonly present in the Mediterranean diet was assessed through three distinct in vitro extraction schemes. Each extraction method provided different results, highlighting the lack of a universal methodology to estimate mercury (Hg) bioaccessibility in those matrices. Bioaccessible Hg fractions ranged from 10 to nearly 90% of total mercury (T-Hg) and increased in predator species (Swordfish - Xiphias gladius, Blue Shark - Prionace glauca and Tuna - Thunnus sp.). Among the three extractions tested, the Unified Bioaccessibility Method (UBM) provided the highest estimation of Hg bioaccessibility for consumers. The tested cooking procedures (frying, grilling and steaming) considerably reduced the bioaccessible fraction. Results indicate that bioaccessible Hg found in ingested fish and seafood is far below the levels set by the current safety risk assessment legislation. These findings highlight the importance of integrating bioaccessibility measurements in food safety legislation.

Assessing the added value of group B Streptococcus maternal immunisation in preventing maternal infection and fetal harm: population surveillance study.

OBJECTIVE: To assess the incidence of maternal group B Streptococcus (GBS) infection in England. DESIGN: Population surveillance augmented through data linkage. SETTING: England. POPULATION: All pregnant women accessing the National Health Service (NHS) in England. METHODS: Invasive GBS (iGBS) infections during pregnancy or within 6 weeks of childbirth were identified by linking Public Health England (PHE) national microbiology surveillance data for 2014 to NHS hospital admission records. Capsular serotypes of GBS were determined by reference laboratory typing of clinical isolates from women aged 15-44 years. Post-caesarean section surgical site infection (SSI) caused by GBS was identified in 21 hospitals participating in PHE SSI surveillance (2009-2015). MAIN OUTCOME MEASURES: iGBS rate per 1000 maternities; risk of GBS SSI per 1000 caesarean sections. RESULTS: Of 1601 patients diagnosed with iGBS infections in England in 2014, 185 (12%) were identified as maternal infections, a rate of 0.29 (95% CI 0.25-0.33) per 1000 maternities and representing 83% of all iGBS cases in women aged 18-44 years. Seven (3.8%) were associated with miscarriage. Fetal outcome identified excess rates of stillbirth (3.4 versus 0.5%) and extreme prematurity (<28 weeks of gestation, 3.7 versus 0.5%) compared with national averages (P < 0.001). Caesarean section surveillance in 27 860 women (21 hospitals) identified 47 cases of GBS SSI, with an estimated 4.24 (3.51-5.07) per 1000 caesarean sections, a median time-to-onset of 10 days (IQR 7-13 days) and ten infections that required readmission. Capsular serotype analysis identified a diverse array of strains with serotype III as the most common (43%). CONCLUSIONS: Our assessment of maternal GBS infection in England indicates the potential additional benefit of GBS vaccination in preventing adverse maternal and fetal outcomes.

Enhancing the resilience of Zostera noltei seagrass meadows against Arenicola spp. bio-invasion: A decision-making approach.

Seagrass meadows provide important and valuable ecosystem services. They are affected by several natural and human-induced stressors, but a combination of natural recovery and management actions have recently inverted the worldwide reduction. The main objectives of this study were to provide science-based knowledge on ecology and restoration, framed on environmental-related policies. By coupling the general guidelines with practical experience, obtained from sequential in situ experiments carried out for several months in a show-case study area, this study provides guidelines useful for restoration practitioners. A decision-making approach is proposed to answer the following questions: 1) What is the best Zostera noltei transplanting method? 2) What is the best technique to reduce the bioturbation activity of Arenicola spp.?, 3) Do bioturbation reduction techniques affect the survival rate of Z. noltei transplants?, and finally, 4) What are the key steps to maximize the success of a Z. noltei transplant and increase the species' resilience? Having a Portuguese coastal lagoon as show-case (Mira Channel, Ria de Aveiro), different transplant and restoration methodologies were tested (i.e. metal frames, nails, bamboo sticks, shoots inserted unanchored into the sediment, and intact units of sediment with seagrasses, named as SODs) to assure low environmental impact on donor meadows, high survival rate of transplanted shoots and the recovery of fragmented or lost meadows. Moreover, to potentially reverse a degraded Arenicola spp. colonized seagrass habitat, different types of natural membranes were tested. Results showed that the best transplanting method is the use of SODs as the self-facilitation process of Z. noltei is enhanced, while being the least invasive for the donor population. The use of a natural membrane can significantly decrease the bioturbation stress caused by Arenicola spp., with jute membrane being the best option, given its cost-handling-benefit trade-offs. Enhancing the success of seagrass restoration requires the implementation of effective measures by environmental restoration practitioners. We defined a three-step process to improve the resilience of Z. noltei. This stepwise approach consists on 1) Characterization of the donor population, 2) Identification of the constraints and implementation of measures to prevent them, and 3) Scale-up the restoration plan. The application of this stepwise approach in intertidal coastal and estuarine systems management will, therefore, facilitate the success of Z. noltei restoration plans.

Precision Constraints for Three-Flavor Neutrino Oscillations from the Full MINOS+ and MINOS Dataset.

We report the final measurement of the neutrino oscillation parameters Δm_{32}^{2} and sin^{2}θ_{23} using all data from the MINOS and MINOS+ experiments. These data were collected using a total exposure of 23.76×10^{20} protons on target producing ν_{µ} and ν[over ¯]_{µ} beams and 60.75 kt yr exposure to atmospheric neutrinos. The measurement of the disappearance of ν_{µ} and the appearance of ν_{e} events between the Near and Far detectors yields |Δm_{32}^{2}|=2.40_{-0.09}^{+0.08}(2.45_{-0.08}^{+0.07})×10^{-3} eV^{2} and sin^{2}θ_{23}=0.43_{-0.04}^{+0.20}(0.42_{-0.03}^{+0.07}) at 68% C.L. for normal (inverted) hierarchy.

Improved Constraints on Sterile Neutrino Mixing from Disappearance Searches in the MINOS, MINOS+, Daya Bay, and Bugey-3 Experiments.

Searches for electron antineutrino, muon neutrino, and muon antineutrino disappearance driven by sterile neutrino mixing have been carried out by the Daya Bay and MINOS+ collaborations. This Letter presents the combined results of these searches, along with exclusion results from the Bugey-3 reactor experiment, framed in a minimally extended four-neutrino scenario. Significantly improved constraints on the θ_{µe} mixing angle are derived that constitute the most constraining limits to date over five orders of magnitude in the mass-squared splitting Δm_{41}^{2}, excluding the 90% C.L. sterile-neutrino parameter space allowed by the LSND and MiniBooNE observations at 90% CL_{s} for Δm_{41}^{2}<13 eV^{2}. Furthermore, the LSND and MiniBooNE 99% C.L. allowed regions are excluded at 99% CL_{s} for Δm_{41}^{2}<1.6 eV^{2}.

A protracted iGAS outbreak in a long-term care facility 2014-2015: control measures and the use of whole-genome sequencing.

BACKGROUND: In 2014, two residents of a long-term care facility (LTCF) developed invasive group A streptococcal (iGAS) infections with identical typing (emm 11), resulting in one death. The second resident recovered but had a subsequent episode of emm 11 iGAS infection 10 months later. This second episode was linked to a third case, within 12 days, leading to a further outbreak investigation. AIM: To combine different techniques to establish whether this was a protracted outbreak, understand transmission pathways and inform appropriate control measures. METHODS: Following a routine response to the first cluster, the second investigation included a care record review. This informed network analysis of case interactions with staff and visitors during 10 days prior to infection. These data were combined with post-outbreak whole-genome sequencing (WGS) using isolates from cases, and staff and resident screening (44 GAS isolates: 11 outbreak-related and 33 sporadic isolates). FINDINGS: Two of the three confirmed iGAS cases died (one suffered two episodes). All iGAS cases, and six non-invasive isolates from 2015, were emm 11 (monophylogenetic WGS clade). Network analysis highlighted only indirect contact through staff-visitor interactions between iGAS cases in 2015. This suggested a common source and transmission propagation through carriage and/or environmental contamination over an 11-month period. CONCLUSIONS: This outbreak highlighted benefits of staff/resident screening and typing as part of routine response. Network analysis and highly discriminatory WGS clarified the protracted nature of the outbreak, supporting findings of hygiene and infection control issues and adding to our understanding of the epidemiology.

1,8-cineole and castor oil in sodium lauryl ether sulphate disrupt reproduction and ovarian tissue of Rhipicephalus (Boophilus) microplus.

Essential and fixed oils have been researched as alternatives to chemical acaricides. The activity of volatile compounds from essential oils (1,8-cineole, citral and eugenol) at 1.0% (w/v) and fixed oil (castor oil) at 0.3% (w/v) dissolved in 2.0% (v/v) dimethyl sulfoxide (DMSO) + 0.2% (w/v) Tween 80® was assessed against Rhipicephalus microplus using immersion tests. 1,8-cineole (29.0%) and castor oil (30.2%) had the highest reproductive inhibition rate. A second experiment was performed to verify the effect of the 1,8-cineole (10.0% w/v) and, or castor oil (0.3% w/v) on tick reproduction using different solubilizing agents. The highest reproductive inhibition was observed for the combination of 1,8-cineole/castor oil (94.1%) and 1,8-cineole in 2.0% (w/v) sodium lauryl ether sulphate (SLES) (92.8%). A third experiment showed morphological changes in R. microplus oocytes at different stages of development, as well as in pedicel cells. The most intense effects were observed when ticks were immersed in the formulation containing 1,8-cineole (10.0% w/v) and castor oil (0.3% w/v) dissolved in 2% (w/v) SLES. These findings highlight the potential of this formulation as an alternative for managing cattle ticks as their cytotoxic effects can reduce R. microplus reproductive success.

Case Report: Portal Vein Thrombosis, Surgical Alternatives in Liver Transplantation.

INTRODUCTION: Liver transplant remains a surgical challenge in cases of portal vein thrombosis. Ten percent of patients listed for liver transplant have this diagnosis preoperatively. Although several techniques of portal revascularization are available, sometimes the best result is not achieved, depending on the extent of thrombosis. OBJECTIVE: The aim of this article is to report our experience in 2 particular cases of liver transplant with portal vein thrombosis. MATERIAL AND METHODS: We present the cases of 2 patients with partial portal thrombosis that extended to the porto-spleno-mesenteric system. The first case is a 36-year-old woman with recurrence of autoimmune liver disease requiring a second graft; the second case concerns a 64-year-old man with alcoholic liver cirrhosis. RESULTS: Both patients had a splenorenal shunt. A portal bypass with a Y venous graft was performed using the cavoiliac veins of the donor. The anastomosis was performed to the superior mesenteric and left renal veins. DISCUSSION AND CONCLUSIONS: These clinical cases demonstrate that portal vein thrombosis is not an absolute contraindication for transplantation and that surgical alternatives exist in cases of grade III portal vein thrombosis.

Innovative tailor made dextran based membranes with excellent non-inflammatory response: In vivo assessment.

In this work, dextran based membranes with potential to be used as implantable devices in Tissue Engineering and Regenerative Medicine (TERM) were prepared by a straightforward strategy. Briefly, two polymers approved by the Food and Drug Administration, viz. dextran and poly(ε-caprolactone) (PCL) were functionalized with methacrylate moieties, and subjected to photocrosslinking. Employing different weight ratios of each polymer in the formulations allowed to obtain transparent membranes with tunable physicochemical properties and low adverse host tissue response. Independently of the material, all formulations have shown to be thermally stable up to 300 °C whilst variations in the polymer ratio resulted in membranes with different glass transition temperatures (Tg) and flexibility. The swelling capacity ranged from 50% to 200%. On the other hand, in vitro hydrolytic degradation did not show to be material-dependent and all membranes maintained their structural integrity for more than 30 days, losing only 8-12% of their initial weight. Preliminary in vitro biological tests did not show any cytotoxic effect on seeded human dental pulp stem cells (hDPSCs), suggesting that, in general, all membranes are capable of supporting cell adhesion and viability. The in vivo biocompatibility of membranes implanted subcutaneously in rats' dorsum indicate that M100/0 (100%wt dextran) and M25/75 (25 %wt dextran) formulations can be classified as "slight-irritant" and "non-irritant", respectively. From the histological analysis performed on the main tissue organs it was not possible to detect any signs of fibrosis or necrosis thereby excluding the presence of toxic degradation by-products deposited or accumulated in these tissues. In combination, these results suggest that the newly developed formulations hold great potential as engineered devices for biomedical applications, where the biological response of cells and tissues are greatly dependent on the physical and chemical cues provided by the substrate.

[Hemiconvulsion-hemiplegia-epilepsy syndrome: case report and use of dextromethorphan]. / Síndrome de hemiconvulsión-hemiplejía-epilepsia: caso clínico y uso de dextrometorfano.

TITLE: Síndrome de hemiconvulsión-hemiplejía-epilepsia: caso clínico y uso de dextrometorfano.

Neurodevelopmental outcome predictors of term newborns with neonatal seizures. / Predictores pronósticos de desarrollo neurológico en recién nacidos a término con crisis neonatales.

INTRODUCTION: The concrete burden of neonatal seizures in neurodevelopmental outcome of term newborns is still unknown in literature. The aim of this study was to describe prognostic predictors in neonatal seizures. SUBJECTS AND METHODS: Observational prospective study of term neonates with clinical seizures from a tertiary center (2009-2018). Adverse outcome was determined as death, global developmental delay, cerebral palsy or epilepsy. Perinatal characteristics, etiology, electrographic features, neuroimaging and antiepileptic treatment were analyzed in a logistic regression model. RESULTS: A total of 102 newborns were included (52 infants with normal outcome). Twelve fatalities were registered. In the survival group, 38 children had an adverse outcome (28 global developmental delay, 27 cerebral palsy, 21 epilepsy). From the prognostic variables identified in univariate analysis, perinatal complications, seizure onset in the first day of life, moderate to severe abnormal background activity, abnormal amplitude-integrated EEG pattern, and treatment response remained independently associated with adverse outcome after a logistic regression model. CONCLUSIONS: There is conflicting data about surrogate markers in neonatal seizures. Aside from confirming the predictive value of previously described variables, we observed that amplitude-integrated EEG monitoring is a forthcoming prognostic tool. Future approaches may include a wider use of amplitude-integrated EEG monitoring, being crucial for timely seizure identification and prompt treatment.

TITLE: Predictores pronósticos de desarrollo neurológico en recién nacidos a término con crisis neonatales.Introducción. El peso específico de las crisis neonatales en el pronóstico neurológico de recién nacidos a término no se conoce bien, por lo que el objetivo del estudio era describir predictores pronósticos en crisis neonatales. Sujetos y métodos. Estudio observacional prospectivo de recién nacidos a término con crisis clínicas en un centro terciario (2009-2018). Pronóstico adverso se definió como muerte, retraso global del desarrollo, parálisis cerebral o epilepsia. Se analizaron las características perinatales, la etiología, los hallazgos electroencefalográficos, la neuroimagen y los tratamientos antiepilépticos siguiendo un modelo de regresión logística. Resultados. Se incluyó a un total de 102 recién nacidos (52 de los cuales tenían desarrollo normal). Se registraron 12 fallecimientos. En el grupo de supervivientes, 38 niños tuvieron un pronóstico desfavorable (28 con retraso global del desarrollo, 27 con parálisis cerebral, 21 con epilepsia). De las variables pronósticas identificadas en el análisis univariante, las complicaciones perinatales, el inicio de las crisis en el primer día de vida, la actividad basal anormal moderada a grave, un patrón anormal en el electroencefalograma de amplitud integrada y la respuesta al tratamiento continuaron mostrándose como independientemente asociadas a pronóstico adverso después de aplicar un modelo de regresión logística. Conclusiones. Existen datos contradictorios sobre marcadores subrogados en crisis neonatales. Aparte de confirmar el valor predictivo de variables previamente descritas, se halló que la monitorización con electroencefalograma de amplitud integrada constituye una prometedora herramienta diagnóstica. En el futuro, se debería extender su utilización en el abordaje de estos pacientes, lo que sería de vital importancia para un diagnóstico y un tratamiento precoces.

Advances on assessing nanotoxicity in marine fish - the pros and cons of combining an ex vivo approach and histopathological analysis in gills.

The need to overcome logistic and ethical limitations of in vivo nanotoxicity evaluation in marine organisms is essential, mostly when dealing with fish. It is well established that medium/solvent conditions affect dispersion and agglomeration of nanoparticles (NPs), which represents a constraint towards a solid and realistic toxicity appraisal. In this way the pros and cons of an ex vivo approach, using a simplified exposure medium (seawater) and addressing gills histopathology, were explored. The nanotoxic potential of environmentally realistic concentrations of titanium dioxide NPs (TiO2 NPs) was also assessed, disclosing the morpho-functional effects on the gills and the possible uptake/elimination processes. Excised gills of the Senegalese sole (Solea senegalensis) were directly exposed in artificial seawater to 20 and 200 µg L-1 TiO2 NPs, for 2 h and 4 h. Semi-quantitative and quantitative histological analyses were applied. The normal morphology of the gill's epithelia was only slightly altered in the control, reflecting protective mechanisms against the artificiality of the experimental conditions, which, together with the absence of differences in the global histopathological index (Ih), corroborated that the gill's morpho-functional features were not compromised, thereby validating the proposed ex vivo approach. TiO2 NPs induced moderate severity and dissemination of histopathological lesions. After 2 h, a series of compensatory mechanisms occurred in NP treatments, implying an efficient response of the innate defense system (increasing number of goblet cells) and effective osmoregulatory ability (chloride cells proliferation). After 4 h, gills revealed signs of recovery (normalization of the number of chloride and goblet cells; similar Ih), highlighting the tissue viability and effective elimination and/or neutralization of NPs. The uptake of the TiO2 NPs seemed to be favored by the higher particle sizes. Overall, the proposed approach emerged as a high-throughput, reliable, accurate and ethically commendable methodology for nanotoxicity assessment in marine fish.

Real-time whole genome sequencing to control a Streptococcus pyogenes outbreak at a national orthopaedic hospital.

BACKGROUND: Whole genome sequencing (WGS) of Streptococcus pyogenes linked to invasive disease has been used to identify and investigate outbreaks. The clinical application of WGS in real-time for outbreak control is seldom employed. AIMS: A fatal case of bacteraemia at a national orthopaedic hospital prompted an outbreak investigation to identify carriers and halt transmission using real-time WGS. METHODS: Retrospective surveillance was conducted to identify patients with Streptococcus pyogenes infections in the last year. Upon contact tracing, four patients and 179 staff were screened for Streptococcus pyogenes carriage. All isolates identified were emm-typed. WGS was performed in real-time on a subset of isolates. FINDINGS: Twelve isolates of Streptococcus pyogenes from the index case, two patients and eight staff were identified. Six isolates were emm 1.0, including the index case and five staff isolates. The remaining isolates belonged to distinct emm types. WGS analysis was undertaken on the six emm 1.0 isolates. Five were indistinguishable by single nucleotide polymorphism (SNP) analysis, with 0 SNP distance, and one had one SNP difference, supporting the hypothesis of recent local transmission. All screen-positive healthcare workers were offered treatment with penicillin or clindamycin. No further cases were identified. CONCLUSION: The increased molecular discrimination of WGS confirmed the clustering of these cases and the outbreak was contained. This demonstrates the clinical utility of WGS in managing outbreaks of invasive Streptococcus pyogenes in real-time and we recommend its implementation as a routine clinical service.

FAIRLANE, a double-blind placebo-controlled randomized phase II trial of neoadjuvant ipatasertib plus paclitaxel for early triple-negative breast cancer.

BACKGROUND: This hypothesis-generating trial evaluated neoadjuvant ipatasertib-paclitaxel for early triple-negative breast cancer (TNBC). PATIENTS AND METHODS: In this randomized phase II trial, patients with early TNBC (T ≥ 1.5 cm, N0-2) were randomized 1 : 1 to receive weekly paclitaxel 80 mg/m2 with ipatasertib 400 mg or placebo (days 1-21 every 28 days) for 12 weeks before surgery. Co-primary end points were pathologic complete response (pCR) rate (ypT0/TisN0) in the intention-to-treat (ITT) and immunohistochemistry phosphatase and tensin homolog (PTEN)-low populations. Secondary end points included pCR rate in patients with PIK3CA/AKT1/PTEN-altered tumors and pre-surgery response rates by magnetic resonance imaging (MRI). RESULTS: pCR rates with ipatasertib versus placebo were 17% versus 13%, respectively, in the ITT population (N = 151), 16% versus 13% in the immunohistochemistry PTEN-low population (N = 35), and 18% versus 12% in the PIK3CA/AKT1/PTEN-altered subgroup (N = 62). Rates of overall and complete response (CR) by MRI favored ipatasertib in all three populations (CR rate 39% versus 9% in the PIK3CA/AKT1/PTEN-altered subgroup). Ipatasertib was associated with more grade ≥3 adverse events (32% versus 16% with placebo), especially diarrhea (17% versus 1%). Higher cycle 1 day 8 (C1D8) immune score was significantly associated with better response only in placebo-treated patients. All ipatasertib-treated patients with low immune scores and a CR had PIK3CA/AKT1/PTEN-altered tumors. CONCLUSIONS: Adding ipatasertib to 12 weeks of paclitaxel for early TNBC did not clinically or statistically significantly increase pCR rate, although overall response rate by MRI was numerically higher with ipatasertib. The antitumor effect of ipatasertib was most pronounced in biomarker-selected patients. Safety was consistent with prior experience of ipatasertib-paclitaxel. A T-cell-rich environment at C1D8 had a stronger association with improved outcomes in paclitaxel-treated patients than seen for baseline tumor-infiltrating lymphocytes. This dependency may be overcome with the addition of AKT inhibition, especially in patients with PIK3CA/AKT1/PTEN-altered tumors. CLINICALTRIALS.GOV: NCT02301988.

Search for Sterile Neutrinos in MINOS and MINOS+ Using a Two-Detector Fit.

A search for mixing between active neutrinos and light sterile neutrinos has been performed by looking for muon neutrino disappearance in two detectors at baselines of 1.04 and 735 km, using a combined MINOS and MINOS+ exposure of 16.36×10^{20} protons on target. A simultaneous fit to the charged-current muon neutrino and neutral-current neutrino energy spectra in the two detectors yields no evidence for sterile neutrino mixing using a 3+1 model. The most stringent limit to date is set on the mixing parameter sin^{2}θ_{24} for most values of the sterile neutrino mass splitting Δm_{41}^{2}>10^{-4} eV^{2}.

Single centre experience of bilateral gracilis flap perineal reconstruction following extra-levator abdominoperineal excision.

AIM: A variety of tissue flaps have been described for the closure of perineal wounds following abdominoperineal excision of the rectum (APE) or exenteration for locally advanced/recurrent rectal cancer and salvage surgery for anal cancer. The aim of this study was to demonstrate the utility of the bilateral pedicled gracilis muscle flaps (BPGMFs) as a reconstruction option in these patients. This is of particular benefit when using a laparoscopic approach for the abdominal component of the operation, avoiding disruption of the abdominal wall and risk of herniation with other reconstruction options, e.g. vertical rectus abdominis myocutaneous flaps. METHOD: This is a retrospective single centre case series of patients who underwent reconstruction of perineal defects using BPGMFs using a novel weave technique, from January 2008 to August 2017. RESULTS: There were 25 patients (16 female), with a median follow-up of 19 months (3-102). The indications for BPGMFs were cancer resection (21) and perineal hernia (4). The median length of stay was 14 days (6-60). All-cause mortality was 36% within the follow-up period. A healed perineal wound was achieved in 72% of patients within 30 days (84% of patients received neoadjuvant chemoradiotherapy). The overall donor site complication rate was 20% (including infection, dehiscence, numbness, haematoma and seroma) and 28% for the perineal site (including infection, dehiscence and prolapse). CONCLUSIONS: BPGMFs provide an important option for reconstruction of the perineum particularly with a minimally invasive approach or with two stomas.