On the IYB-property in some solvable groups

A finite group G is called Involutive Yang-Baxter (IYB) if there exists a bijective 1-cocycle χ:G⟶M for some ZG -module M. It is known that every IYB-group is solvable, but it is still an open question whether the converse holds. A characterization of the IYB property by the existence of an ideal I in the augmentation ideal ωZG complementing the set 1−G leads to some speculation that there might be a connection with the isomorphism problem for ZG . In this paper we show that if N is a nilpotent group of class two and H is an IYB-group of order coprime to that of N, then N⋊H is IYB. The class of groups that can be obtained in that way (and hence are IYB) contains in particular Hertweck’s famous counterexample to the isomorphism conjecture as well as all of its subgroups. We then investigate what an IYB structure on Hertweck’s counterexample looks like concretely

Sebomic identification of sex- and ethnicity-specific variations in residual skin surface components (RSSC) for bio-monitoring or forensic applications

Background: “Residual skin surface components” (RSSC) is the collective term used for the superficial layer of sebum, residue of sweat, small quantities of intercellular lipids and components of natural moisturising factor present on the skin surface. Potential applications of RSSC include use as a sampling matrix for identifying biomarkers of disease, environmental exposure monitoring, and forensics (retrospective identification of exposure to toxic chemicals). However, it is essential to first define the composition of “normal” RSSC. Therefore, the aim of the current study was to characterise RSSC to determine commonalities and differences in RSSC composition in relation to sex and ethnicity. Methods: Samples of RSSC were acquired from volunteers using a previously validated method and analysed by high-pressure liquid chromatography–atmospheric pressure chemical ionisation–mass spectrometry (HPLC-APCI-MS). The resulting data underwent sebomic analysis. Results: The composition and abundance of RSSC components varied according to sex and ethnicity. The normalised abundance of free fatty acids, wax esters, diglycerides and triglycerides was significantly higher in males than females. Ethnicity-specific differences were observed in free fatty acids and a diglyceride. Conclusions: The HPLC-APCI-MS method developed in this study was successfully used to analyse the normal composition of RSSC. Compositional differences in the RSSC can be attributed to sex and ethnicity and may reflect underlying factors such as diet, hormonal levels and enzyme expression.Peer reviewedFinal Published versio

The identification of proteoglycans and glycosaminoglycans in archaeological human bones and teeth

Bone tissue is mineralized dense connective tissue consisting mainly of a mineral component (hydroxyapatite) and an organic matrix comprised of collagens, non-collagenous proteins and proteoglycans (PGs). Extracellular matrix proteins and PGs bind tightly to hydroxyapatite which would protect these molecules from the destructive effects of temperature and chemical agents after death. DNA and proteins have been successfully extracted from archaeological skeletons from which valuable information has been obtained; however, to date neither PGs nor glycosaminoglycan (GAG) chains have been studied in archaeological skeletons. PGs and GAGs play a major role in bone morphogenesis, homeostasis and degenerative bone disease. The ability to isolate and characterize PG and GAG content from archaeological skeletons would unveil valuable paleontological information. We therefore optimized methods for the extraction of both PGs and GAGs from archaeological human skeleto ns. PGs and GAGs were successfully extracted from both archaeological human bones and teeth, and characterized by their electrophoretic mobility in agarose gel, degradation by specific enzymes and HPLC. The GAG populations isolated were chondroitin sulfate (CS) and hyaluronic acid (HA). In addition, a CSPG was detected. The localization of CS, HA, three small leucine rich PGs (biglycan, decorin and fibromodulin) and glypican was analyzed in archaeological human bone slices. Staining patterns were different for juvenile and adult bones, whilst adolescent bones had a similar staining pattern to adult bones. The finding that significant quantities of PGs and GAGs persist in archaeological bones and teeth opens novel venues for the field of Paleontology

Novel compound heterozygous STN1 variants are associated with Coats Plus syndrome

Funder: WellcomeAbstract: Aim: Coats plus syndrome (CP) is a rare autosomal recessive disorder, characterised by retinal telangiectasia exudates (Coats disease), leukodystrophy, distinctive intracranial calcification and cysts, as well as extra‐neurological features including abnormal vasculature of the gastrointestinal tract, portal hypertension and osteopenia with a tendency to fractures. CP most frequently occurs due to loss‐of‐function mutations in CTC1. The encoded protein CTC1 constitutes part of the CST (CTC1‐STN1‐TEN1) complex, and three patients have been described with CP due to biallelic mutations in STN1. Together with the identification of homozygosity for a specific loss‐of‐function mutation in POT1 in a sibling pair, these observations highlight a defect in the maintenance of telomere integrity as the cause of CP, although the precise mechanism leading to the micro‐vasculopathy seen at a pathological level remains unclear. Here, we present the investigation of a fourth child who presented to us with retinal exudates, intracranial calcifications and developmental delay, in keeping with a diagnosis of CP, and later went on to develop pancytopenia and gastrointestinal bleeding. Genome sequencing revealed compound heterozygous variants in STN1 as the likely genetic cause of CP in this present case. Methods: We assessed the phenotype to be CP and undertook targeted sequencing. Results: Whilst sequencing of CTC1 and POT1 was normal, we identified novel compound heterozygous variants in STN1 (previous gene symbol OBFC1): one loss‐of‐function––c.894dup (p.(Asp299Argfs*58)); and one missense––c.707T>C (p.(Leu236Pro)). Conclusion: Given the clinical phenotype and identified variants we suggest that this is only the fourth patient reported to date with CP due to mutations in STN1

Tracking health system performance in times of crisis using routine health data: lessons learned from a multicountry consortium

COVID-19 has prompted the use of readily available administrative data to track health system performance in times of crisis and to monitor disruptions in essential healthcare services. In this commentary we describe our experience working with these data and lessons learned across countries. Since April 2020, the Quality Evidence for Health System Transformation (QuEST) network has used administrative data and routine health information systems (RHIS) to assess health system performance during COVID-19 in Chile, Ethiopia, Ghana, Haiti, Lao People's Democratic Republic, Mexico, Nepal, South Africa, Republic of Korea and Thailand. We compiled a large set of indicators related to common health conditions for the purpose of multicountry comparisons. The study compiled 73 indicators. A total of 43% of the indicators compiled pertained to reproductive, maternal, newborn and child health (RMNCH). Only 12% of the indicators were related to hypertension, diabetes or cancer care. We also found few indicators related to mental health services and outcomes within these data systems. Moreover, 72% of the indicators compiled were related to volume of services delivered, 18% to health outcomes and only 10% to the quality of processes of care. While several datasets were complete or near-complete censuses of all health facilities in the country, others excluded some facility types or population groups. In some countries, RHIS did not capture services delivered through non-visit or nonconventional care during COVID-19, such as telemedicine. We propose the following recommendations to improve the analysis of administrative and RHIS data to track health system performance in times of crisis: ensure the scope of health conditions covered is aligned with the burden of disease, increase the number of indicators related to quality of care and health outcomes; incorporate data on nonconventional care such as telehealth; continue improving data quality and expand reporting from private sector facilities; move towards collecting patient-level data through electronic health records to facilitate quality-of-care assessment and equity analyses; implement more resilient and standardized health information technologies; reduce delays and loosen restrictions for researchers to access the data; complement routine data with patient-reported data; and employ mixed methods to better understand the underlying causes of service disruptions

Detailed dimethylacetal and fatty acid composition of rumen content from lambs fed lucerne or concentrate supplemented with soybean oil

Articles in International JournalsLipid metabolism in the rumen is responsible for the complex fatty acid profile of rumen outflow compared with the dietary fatty acid composition, contributing to the lipid profile of ruminant products. A method for the detailed dimethylacetal and fatty acid analysis of rumen contents was developed and applied to rumen content collected from lambs fed lucerne or concentrate based diets supplemented with soybean oil. The methodological approach developed consisted on a basic/ acid direct transesterification followed by thin-layer chromatography to isolate fatty acid methyl esters from dimethylacetal, oxo- fatty acid and fatty acid dimethylesters. The dimethylacetal composition was quite similar to the fatty acid composition, presenting even-, odd- and branched-chain structures. Total and individual odd- and branched-chain dimethylacetals were mostly affected by basal diet. The presence of 18:1 dimethylacetals indicates that biohydrogenation intermediates might be incorporated in structural microbial lipids. Moreover, medium-chain fatty acid dimethylesters were identified for the first time in the rumen content despite their concentration being relatively low. The fatty acids containing 18 carbon-chain lengths comprise the majority of the fatty acids present in the rumen content, most of them being biohydrogenation intermediates of 18:2n26 and 18:3n23. Additionally, three oxo- fatty acids were identified in rumen samples, and 16-O-18:0 might be produced during biohydrogenation of the 18:3n23

Methotrexate used in combination with aminolaevulinic acid for photodynamic killing of prostate cancer cells

Photodynamic therapy (PDT) using 5-aminolaevulinic acid (ALA) to drive production of an intracellular photosensitiser, protoporphyrin IX (PpIX), is a promising cancer treatment. However, ALA-PDT is still suboptimal for thick or refractory tumours. Searching for new approaches, we tested a known inducer of cellular differentiation, methotrexate (MTX), in combination with ALA-PDT in LNCaP cells. Methotrexate alone promoted growth arrest, differentiation, and apoptosis. Methotrexate pretreatment (1 mg l−1, 72 h) followed by ALA (0.3 mM, 4 h) resulted in a three-fold increase in intracellular PpIX, by biochemical and confocal analyses. After exposure to 512 nm light, killing was significantly enhanced in MTX-preconditioned cells. The reverse order of treatments, ALA-PDT followed by MTX, yielded no enhancement. Methotrexate caused a similar relative increase in PpIX, whether cells were incubated with ALA, methyl-ALA, or hexyl-ALA, arguing against a major effect upon ALA transport. Searching for an effect among porphyrin synthetic enzymes, we found that coproporphyrinogen oxidase (CPO) was increased three-fold by MTX at the mRNA and protein levels. Transfection of LNCaP cells with a CPO-expressing vector stimulated the accumulation of PpIX. Our data suggest that MTX, when used to modulate intracellular production of endogenous PpIX, may provide a new combination PDT approach for certain cancers

Incidence and predictors of hospital readmission in children presenting with severe anaemia in Uganda and Malawi: a secondary analysis of TRACT trial data

Background: Severe anaemia (haemoglobin &lt; 6 g/dL) is a leading cause of recurrent hospitalisation in African children. We investigated predictors of readmission in children hospitalised with severe anaemia in the TRACT trial (ISRCTN84086586) in order to identify potential future interventions.Methods: Secondary analyses of the trial examined 3894 children from Uganda and Malawi surviving a hospital episode of severe anaemia. Predictors of all-cause readmission within 180 days of discharge were identified using multivariable regression with death as a competing risk. Groups of children with similar characteristics were identified using hierarchical clustering.Results: Of the 3894 survivors 682 (18%) were readmitted; 403 (10%) had ≥2 re-admissions over 180 days. Three main causes of readmission were identified: severe anaemia (n = 456), malaria (n = 252) and haemoglobinuria/dark urine syndrome (n = 165). Overall, factors increasing risk of readmission included HIV-infection (hazard ratio 2.48(95% CI 1.63–3.78), p &lt; 0.001); ≥2 hospital admissions in the preceding 12 months (1.44(1.19–1.74), p &lt; 0.001); history of transfusion (1.48(1.13–1.93), p = 0.005); and missing ≥1 trial medication dose (proxy for care quality) (1.43 (1.21–1.69), p &lt; 0.001). Children with uncomplicated severe anaemia (Hb 4-6 g/dL and no severity features),who never received a transfusion (per trial protocol) during the initial admission had a substantially lower risk of readmission (0.67(0.47–0.96), p = 0.04). Malaria (among children with no prior history of transfusion) (0.60(0.47–0.76), p &lt; 0.001); younger-age (1.07 (1.03–1.10) per 1 year younger, p &lt; 0.001) and known sickle cell disease (0.62(0.46–0.82), p = 0.001) also decreased risk of readmission. For anaemia re-admissions, gross splenomegaly and enlarged spleen increased risk by 1.73(1.23–2.44) and 1.46(1.18–1.82) respectively compared to no splenomegaly.Clustering identified four groups of children with readmission rates from 14 to 20%. The cluster with the highest readmission rate was characterised by very low haemoglobin (mean 3.6 g/dL). Sickle Cell Disease (SCD) predominated in two clusters associated with chronic repeated admissions or severe, acute presentations in largely undiagnosed SCD. The final cluster had high rates of malaria (78%), severity signs and very low platelet count, consistent with acute severemalaria.Conclusions: Younger age, HIV infection and history of previous hospital admissions predicted increased risk of readmission. However, no obvious clinical factors for intervention were identified. As missing medication doses was highly predictive, attention to care related factors may be important.Trial registration: ISRCTN ISRCTN84086586.Keywords: Severe anaemia, Readmission</p

EpiNet as a way of involving more physicians and patients in epilepsy research: Validation study and accreditation process

open185siObjective: EpiNet was established to encourage epilepsy research. EpiNet is used for multicenter cohort studies and investigator-led trials. Physicians must be accredited to recruit patients into trials. Here, we describe the accreditation process for the EpiNet-First trials. Methods: Physicians with an interest in epilepsy were invited to assess 30 case scenarios to determine the following: whether patients have epilepsy; the nature of the seizures (generalized, focal); and the etiology. Information was presented in two steps for 23 cases. The EpiNet steering committee determined that 21 cases had epilepsy. The steering committee determined by consensus which responses were acceptable for each case. We chose a subset of 18 cases to accredit investigators for the EpiNet-First trials. We initially focused on 12 cases; to be accredited, investigators could not diagnose epilepsy in any case that the steering committee determined did not have epilepsy. If investigators were not accredited after assessing 12 cases, 6 further cases were considered. When assessing the 18 cases, investigators could be accredited if they diagnosed one of six nonepilepsy patients as having possible epilepsy but could make no other false-positive errors and could make only one error regarding seizure classification. Results: Between December 2013 and December 2014, 189 physicians assessed the 30 cases. Agreement with the steering committee regarding the diagnosis at step 1 ranged from 47% to 100%, and improved when information regarding tests was provided at step 2. One hundred five of the 189 physicians (55%) were accredited for the EpiNet-First trials. The kappa value for diagnosis of epilepsy across all 30 cases for accredited physicians was 0.70. Significance: We have established criteria for accrediting physicians using EpiNet. New investigators can be accredited by assessing 18 case scenarios. We encourage physicians with an interest in epilepsy to become EpiNet-accredited and to participate in these investigator-led clinical trials.openBergin P.S.; Beghi E.; Sadleir L.G.; Brockington A.; Tripathi M.; Richardson M.P.; Bianchi E.; Srivastava K.; Jayabal J.; Legros B.; Ossemann M.; McGrath N.; Verrotti A.; Tan H.J.; Beretta S.; Frith R.; Iniesta I.; Whitham E.; Wanigasinghe J.; Ezeala-Adikaibe B.; Striano P.; Rosemergy I.; Walker E.B.; Alkhidze M.; Rodriguez-Leyva I.; Ramirez Gonzalez J.A.; D'Souza W.J.; Calle A.; Palacios C.; Cairns A.; Carney P.; Craig D.; Gill D.; Gupta S.; Lander C.; Laue-Gizzi H.; Hitchens N.; Kiley M.; Lawn N.; Reyneke E.; Riney K.; Tan M.; Tan M.; Thieban M.; Wong C.; van Rijckevorsel G.; Ferrari Strang A.G.; Gifoni A.; Helio L.; Monnerat B.; Brna P.; Donner E.; Jacques S.; Jette N.; McLachlan R.; Mohamed I.; Tran T.P.Y.; Bo X.; Fan S.; Guang Y.; Li M.; Wang K.; Zhang S.; Ladino L.; Christensen J.; Kӧlmel M.S.; Nikanorova M.; Uusitalo A.; Vieira P.; Auvin S.; Ediberidze T.; Gogatishvili N.; Jishkariani T.; Dennig D.; Grimmer A.; Michaelis R.; Schubert-Bast S.; Stephani C.; Stodieck S.; Vollbrandt M.; Zellner A.; Zafeiriou D.; Fogarasi A.; Halasz P.; Chaurasia R.N.; Jain S.; Nair R.; Passi P.; Rajadhyaksha S.; Sattaluri S.J.; Shah H.; Udani V.; Costello D.; Aguglia U.; Bartocci A.; Benna P.; Ferlazzo E.; Laino D.; Spalice A.; Zanchi C.; Ali A.; Lim K.S.; Ramirez A.; Anderson N.; Barber A.; Cariga P.; Cleland J.; Child N.; Davis S.; Dayal V.; Dickson C.; Doran J.; Duncan R.; Giri P.; Herd M.; Hutchinson D.; Jones B.; Kao J.; Kilfoyle D.; Mottershead J.; Muir C.; Nolan M.; Pereira J.; Ranta A.; Sadani S.; Simpson M.; Spooner C.; Timmings P.; Walker E.; Wei D.; Willoughby E.; Wong E.; Wu T.; Olusola T.; Mahmud H.; Mogul Z.; Espinoza J.; Vizarreta J.H.; Baeta E.M.; Teotonio R.; Jocic-Jakubi B.; Lukic S.; Korosec M.; Zgur T.; Eguilaz M.G.; Asztely F.; Sithinamsuwan P.; Anderson J.; Auce P.; Desurkar A.; Hamandi K.; Kelso A.; Sanchez V.; Sidra A.; Smith P.; Wehner T.; Winston G.; Andrade E.; Bensalem-Owen M.; Boudreau M.; Caller T.; Chapman K.; Chari G.; Davis K.; Droker B.; El-Hagrassy M.; Eliashiv D.; Eze C.; Heck C.; Kabir A.; Kolesnik D.; Lam A.; Lopez J.; Maamoon T.; Cohen J.M.; Maganti R.; Nwankwo C.; Park K.; Proteasa S.; Sandok E.; Seinfield S.; Toub J.; Wirrell E.; Arbildi M.; Thien T.T.Bergin, P. S.; Beghi, E.; Sadleir, L. G.; Brockington, A.; Tripathi, M.; Richardson, M. P.; Bianchi, E.; Srivastava, K.; Jayabal, J.; Legros, B.; Ossemann, M.; Mcgrath, N.; Verrotti, A.; Tan, H. J.; Beretta, S.; Frith, R.; Iniesta, I.; Whitham, E.; Wanigasinghe, J.; Ezeala-Adikaibe, B.; Striano, P.; Rosemergy, I.; Walker, E. B.; Alkhidze, M.; Rodriguez-Leyva, I.; Ramirez Gonzalez, J. A.; D'Souza, W. J.; Calle, A.; Palacios, C.; Cairns, A.; Carney, P.; Craig, D.; Gill, D.; Gupta, S.; Lander, C.; Laue-Gizzi, H.; Hitchens, N.; Kiley, M.; Lawn, N.; Reyneke, E.; Riney, K.; Tan, M.; Tan, M.; Thieban, M.; Wong, C.; van Rijckevorsel, G.; Ferrari Strang, A. G.; Gifoni, A.; Helio, L.; Monnerat, B.; Brna, P.; Donner, E.; Jacques, S.; Jette, N.; Mclachlan, R.; Mohamed, I.; Tran, T. P. Y.; Bo, X.; Fan, S.; Guang, Y.; Li, M.; Wang, K.; Zhang, S.; Ladino, L.; Christensen, J.; Kӧlmel, M. S.; Nikanorova, M.; Uusitalo, A.; Vieira, P.; Auvin, S.; Ediberidze, T.; Gogatishvili, N.; Jishkariani, T.; Dennig, D.; Grimmer, A.; Michaelis, R.; Schubert-Bast, S.; Stephani, C.; Stodieck, S.; Vollbrandt, M.; Zellner, A.; Zafeiriou, D.; Fogarasi, A.; Halasz, P.; Chaurasia, R. N.; Jain, S.; Nair, R.; Passi, P.; Rajadhyaksha, S.; Sattaluri, S. J.; Shah, H.; Udani, V.; Costello, D.; Aguglia, U.; Bartocci, A.; Benna, P.; Ferlazzo, E.; Laino, D.; Spalice, A.; Zanchi, C.; Ali, A.; Lim, K. S.; Ramirez, A.; Anderson, N.; Barber, A.; Cariga, P.; Cleland, J.; Child, N.; Davis, S.; Dayal, V.; Dickson, C.; Doran, J.; Duncan, R.; Giri, P.; Herd, M.; Hutchinson, D.; Jones, B.; Kao, J.; Kilfoyle, D.; Mottershead, J.; Muir, C.; Nolan, M.; Pereira, J.; Ranta, A.; Sadani, S.; Simpson, M.; Spooner, C.; Timmings, P.; Walker, E.; Wei, D.; Willoughby, E.; Wong, E.; Wu, T.; Olusola, T.; Mahmud, H.; Mogul, Z.; Espinoza, J.; Vizarreta, J. H.; Baeta, E. M.; Teotonio, R.; Jocic-Jakubi, B.; Lukic, S.; Korosec, M.; Zgur, T.; Eguilaz, M. G.; Asztely, F.; Sithinamsuwan, P.; Anderson, J.; Auce, P.; Desurkar, A.; Hamandi, K.; Kelso, A.; Sanchez, V.; Sidra, A.; Smith, P.; Wehner, T.; Winston, G.; Andrade, E.; Bensalem-Owen, M.; Boudreau, M.; Caller, T.; Chapman, K.; Chari, G.; Davis, K.; Droker, B.; El-Hagrassy, M.; Eliashiv, D.; Eze, C.; Heck, C.; Kabir, A.; Kolesnik, D.; Lam, A.; Lopez, J.; Maamoon, T.; Cohen, J. M.; Maganti, R.; Nwankwo, C.; Park, K.; Proteasa, S.; Sandok, E.; Seinfield, S.; Toub, J.; Wirrell, E.; Arbildi, M.; Thien, T. T