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Context Habitat connectivity is key when designing reserve networks for conservation of species at risk. Acquiring land over time to achieve connectivity for multiple species in a systematic conservation plan can pose a challenge because not all high priority parcels will be acquired, species occurrence data is often limited, and using multiple species models together is complex. Objectives We evaluated four possible land acquisition strategies in a such a plan in their ability to meet each of three objectives. The strategies represent different combinations of what are termed ‘Priority 1’, ‘Priority 2’, and ‘Corridor’ lands in the plan. The objectives are to (1) meet conservation target acreages identified in the plan; these are distinct from connectivity goals, (2) maximize structural habitat connectivity, and (3) maximize connectivity for multiple focal species. Methods For this case study in Yolo County, California, we compared the efficiency of strategies to meet conservation targets using MARXAN. We compared structural connectivity of MARXAN solutions for each strategy using FRAGSTATS and distance between patches using ArcGIS. We compared focal species connectivity by using ArcGIS to define species-specific least cost networks and then assessing each network’s conformity with MARXAN solutions. Results ‘Priority 1’ parcels and ‘Corridor’ parcels together provide (1) the most efficient solution for attaining conservation targets, (2) the highest structural connectivity, and (3) high connectivity for the greatest number of focal species. Conclusions Because land acquisition patterns are time sensitive and data may be limited, we recommend using spatial prioritization software often and employing several measures of connectivity in decision-making.

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Introduction: Distal radius fractures are one of the most common fractures in the United States. Treatment usually involves internal fixation using a volar Henry approach with placement of a volar locking plate. Optimal treatment becomes less apparent when significant bone loss occurs. No case of an open distal radius fracture treated using a staged Masquelet technique involving proximal tibial autograft is available in the literature. Herein, we describe and discuss a case report of a novel technique to treat a large (5 cm) bone defect for an open distal radius fracture. Case Report: A 59-year-old man suffered an open, comminuted, and intra-articular distal radius fracture with 5 cm of bone loss. He was treated using a staged Masquelet technique with incorporation of ipsilateral proximal tibial autograft with a bone harvester to obtain cancellous autograft and bone marrow graft. The patient initially underwent emergent I and D, acute carpal tunnel release, and internal and external fixation. A 5 cm bone void was filled with antibiotic cement. Four weeks later, the antibiotic cement was removed, cancellous bone graft and marrow were harvested from the proximal tibia, and the graft was placed within the prior bone void. Fracture site healing was confirmed radiographically and with computer-tomography imaging 3 months later. The patient has demonstrated excellent results 1 year post-operative with 60° of wrist flexion, 40° of wrist extension with mild pain, and full finger range of motion with radiographic union. Conclusion: Internal fixation with placement of a volar locking plate remains the mainstay of treatment for distal radial fractures. However, in more comminuted fractures with bone loss, treatment becomes more challenging. We have presented a unique case utilizing a staged Masquelet technique with incorporation of a proximal tibial autograft to educate readers on an alternative option and technique for autograft donor sites in these more complicated fractures.

Since its outbreak in early 2020, the COVID-19 pandemic has diverted resources from non-urgent and elective procedures, leading to diagnosis and treatment delays, with an increased number of neoplasms at advanced stages worldwide. The aims of this study were to quantify the reduction in surgical activity for indeterminate thyroid nodules during the COVID-19 pandemic; and to evaluate whether delays in surgery led to an increased occurrence of aggressive tumours. In this retrospective, international, cross-sectional study, centres were invited to participate in June 22, 2022; each centre joining the study was asked to provide data from medical records on all surgical thyroidectomies consecutively performed from Jan 1, 2019, to Dec 31, 2021. Patients with indeterminate thyroid nodules were divided into three groups according to when they underwent surgery: from Jan 1, 2019, to Feb 29, 2020 (global prepandemic phase), from March 1, 2020, to May 31, 2021 (pandemic escalation phase), and from June 1 to Dec 31, 2021 (pandemic decrease phase). The main outcomes were, for each phase, the number of surgeries for indeterminate thyroid nodules, and in patients with a postoperative diagnosis of thyroid cancers, the occurrence of tumours larger than 10 mm, extrathyroidal extension, lymph node metastases, vascular invasion, distant metastases, and tumours at high risk of structural disease recurrence. Univariate analysis was used to compare the probability of aggressive thyroid features between the first and third study phases. The study was registered on ClinicalTrials.gov, NCT05178186. Data from 157 centres (n=49 countries) on 87 467 patients who underwent surgery for benign and malignant thyroid disease were collected, of whom 22 974 patients (18 052 [78·6%] female patients and 4922 [21·4%] male patients) received surgery for indeterminate thyroid nodules. We observed a significant reduction in surgery for indeterminate thyroid nodules during the pandemic escalation phase (median monthly surgeries per centre, 1·4 [IQR 0·6-3·4]) compared with the prepandemic phase (2·0 [0·9-3·7]; p

Supernova remnants (SNRs) contribute to regulate the star formation efficiency and evolution of galaxies. As they expand into the interstellar medium (ISM), they transfer vast amounts of energy and momentum that displace, compress and heat the surrounding material. Despite the extensive work in galaxy evolution models, it remains to be observationally validated to what extent the molecular ISM is affected by the interaction with SNRs. We use the first results of the ESO-ARO Public Spectroscopic Survey SHREC, to investigate the shock interaction between the SNR IC443 and the nearby molecular clump G. We use high sensitivity SiO(2-1) and H$^{13}$CO$^+$(1-0) maps obtained by SHREC together with SiO(1-0) observations obtained with the 40m telescope at the Yebes Observatory. We find that the bulk of the SiO emission is arising from the ongoing shock interaction between IC443 and clump G. The shocked gas shows a well ordered kinematic structure, with velocities blue-shifted with respect to the central velocity of the SNR, similar to what observed toward other SNR-cloud interaction sites. The shock compression enhances the molecular gas density, n(H$_2$), up to $>$10$^5$ cm$^{-3}$, a factor of >10 higher than the ambient gas density and similar to values required to ignite star formation. Finally, we estimate that up to 50\% of the momentum injected by IC443 is transferred to the interacting molecular material. Therefore the molecular ISM may represent an important momentum carrier in sites of SNR-cloud interactions., Accepted for Publication in MNRAS; 11 pages, 7 figures

Study question Which are the determining factors influencing the success rate of egg donation programs with imported vitrified oocytes? Summary answer Number of oocytes available after warming, male BMI and semen characteristics are critical parameters influencing reproductive results of oocyte donation programs with imported vitrified oocytes What is known already The use of vitrified oocytes from foreign banks and the performance of ICSI using fresh sperm from the recipient's partner is a widely used method of heterologous fertilisation. Recent evidence has questioned the overall effectiveness of this approach: vitrification and warming may reduce the number of oocytes available for insemination, resulting in a lower rate of live births per cycle. Recent studies have attempted to define the right clinical strategy to improve the effectiveness of oocyte vitrification cycles, stressing the importance of the number of imported oocytes (8-9 oocytes) and transfer to the blastocyst stage. Study design, size, duration Observational longitudinal cohort study of 431 cycles of oocyte donation conducted between January 2015 and February 2019. A total of 398 couples (mean female age: 43.2 ± 3.5, 28-50 years; mean male age: 44.7 ± 6.1, 28-73 years) underwent an IVF cycle with imported donated vitrified oocytes (mean donor age: 25.2 ± 3.5, 19-34 years). All consecutive oocyte donation cycles conducted at the centre for Reproductive Medicine of the European Hospital in Rome were included. Participants/materials, setting, methods In order to assess which factors are associated with the various outcomes, uni-and multi-variable analyses were conducted. In the multivariable analyses, variables that showed a p value Main results and the role of chance A univariate analysis was carried out showing that among the demographic characteristics studied, the only one that proved significantly able to influence the outcome of the pregnancy test was male BMI. In 49% of unsuccessful cycles, the male BMI was above 25 (p = 0.03). The correlation is confirmed when comparing cycle outcomes in couples with normal/underweight vs overweight/obese men (p = 0.03). The relationship between female or donor BMI and treatment outcome, however, was not statistically significant. The day on which embryo transfer is performed affects the outcome of the cycle: transferring on day 2 compared to day 5 reduces the probability of clinical pregnancy (ET in day 2= positive clinical pregnancy in 4/16 (25%); ET in day 3= 158/307 (51.4%); ET in day 5=40/67 (59.7%). The relationship between male BMI classes and sperm parameters was studied: the distribution of concentration is different in the 3 BMI groups (p = 0.011); in particular, obese men have a significantly lower concentration than normal-weight men (p = 0.006 after Bonferroni correction). There were no statistically significant differences in volume (P = 0.722), morphology (p = 0.100) and motility (p = 0.179), although there was a downward trend in motility, with a reduction in obese subjects compared to normal weight. Limitations, reasons for caution This is an observational study and our findings are in contrast with previous studies which do not show any correlation between male partner BMI categories and reproductive outcomes in egg donation programs. Wider implications of the findings Our study shows that the number of oocytes available after warming, male BMI, semen characteristics and blastocyst transfer are critical parameters able to influence the reproductive outcomes of egg donation programs with imported vitrified oocytes. Trial registration number Not applicable

Study question Could factors inherent to individual centers, related to local clinical or laboratory variables, play a role in the increased incidence of monozygotic twins in IVF? Summary answer The rate of MZT did not significantly vary among IVF centers What is known already The risk of monozygotic twins (MZT) is increased in couples undergoing in vitro fertilization (IVF). Several systematic reviews have investigated the possible determinants linked to IVF, but results obtained have been inconclusive. Associations have been identified with the prolonged culture at blastocyst stage and young female age. Conventional IVF compared to ICSI, and assisted hatching emerged as possible additional risk factors, but evidence is controversial. Meta-analyses, however, cannot provide robust evidence because of the difficulty in performing multivariate analyses. Moreover, available investigations were retrospective and involved relatively small sample sizes hampering the quality of the collected data. Study design, size, duration This is a multicenter retrospective cohort study using the Italian ART National Registry database and involving the Centers reporting data from individual IVF cycles from 2015 to 2019. Eighteen IVF centers were included with a total of 87,076 IVF cycles reported during the study period. The primary aim of the study was to investigate whether the incidence of MZT differed among centers. Participants/materials, setting, methods Only single embryo transfer cycles were considered. Women who had sex-discordant twin deliveries were excluded. MZT rate was calculated as the number of multiple pregnancies out of the total number of clinical pregnancies. A binomial distribution model was used to determine the 95% CI of the frequency of MZT. The rates among centers were deemed heterogeneous if the 95% CI in at least one center did not include the mean MZT rate. Main results and the role of chance Ten centers reported data from 2015 to 2019, eight from 2017 to 2019. An analysis of the main characteristics of the centers revealed considerable variability. The total number of clinical pregnancies fulfilling our inclusion criteria were 10,440. Of these, 7 were found to be twin pregnancies with discordant gender and were excluded, leaving 10,433 for data analyses. The number of cases included per center varied between 11 and 2,823. Overall, 162 pregnancies were found to be multiple: 48 ended in a miscarriage, 28 spontaneously reduced to singletons and 86 women delivered two or more newborns. The vast majority were twins (n = 160), one was triplet, and one was quadruplet. Considering the denominator of 10,433 pregnancies, the rate of MZT was thus 1.5% (95%CI: 1.3 - 1.8%). The MZT rate among centers varied between 0% (95%CI: 0.0 - 25.9%) and 3.2% (95%CI: 1.3 - 8.1%). All the 95%CIs of the rates of MZT include the 1.5% common rate, thus rejecting the hypothesis that this incidence significantly differed among centers. Spearman correlations between the rate of MZT and variables associated with individual center policies could not identify any significant association. Even when restricting the analyses only to the largest centers, no association emerged. Limitations, reasons for caution Our study was limited by its retrospective nature. Furthermore, some centers provided less than 100 cases for data analysis and were therefore poorly informative. External confirmation from larger registries is therefore required. Wider implications of the findings This study provides evidences that the rate of MZT did not differ among IVF centers. Furthermore, no clinical and laboratory variables inherent to individual centers were identified in the determinism of IVF-associated MZT. Further studies are needed to identify the causes of increased risk of MZT in IVF practice. Trial registration number not applicable

Study question Do kinetic parameters change among euploid, mosaic and aneuploid blastocysts? Is the KIDscoreTMDay5 version 3.0 (KS-5.3) correlated to preimplantation genetic testing for aneuploidies (PGT-A) results? Summary answer The KS-5.3 differs in embryo ploidy classes. The analysis of the kinetic variables showed that the aneuploid embryos were significantly slower than euploid and mosaic. What is known already Chromosomal abnormalities affect more than 50% of embryos in women with >35 years of age and PGT-A is the best way to predict embryo’s ploidy status decreasing implantation failure and miscarriage. However, this procedure is not always possible due to social or moral issues. So, the use of the non-invasive time lapse monitoring could be helpful to determine the morphokinetic characteristics in the different ploidy classes. KS-5.3 (vitrolife,Sweden) is a scoring model based on morphokinetic data, developed to predict the pregnancy rate of day-5 blastocysts. Recent publications showed differences in kinetic parameters between euploid and aneuploid embryos. Study design, size, duration This retrospective study analyzed 728 blastocysts with PGT-A results obtained at Villa Mafalda Clinic from May 2020 to June 2021. Embryos were cultured in EmbryoScope+ time-lapse system (Vitrolife) at 37 °C, 6%CO2, and 5% O2. The PGT-A was performed using next-generation sequence (NGS) technology on the trophectoderm biopsy sample on day 5/6/7. Automatic annotations for division times and quality gradings were performed by senior embryologists and all kinetic values were reported in hours post microinjection. Participants/materials, setting, methods 728 blastocysts were classified in: (E) euploid (n = 172), (M) mosaicism (n = 171) and (A) aneuploid (n = 385). In this study, they were considered KS-5.3 and the following kinetic variables: the time to reach 2 cells (t2), 3 cells (t3), 4 cells (t4), 5 cells (t5), and the blastocyst formation (TB). Continuous variables were reported as the median and interquartile range (IQR). For the statistical analysis, nonparametric tests were performed and p Main results and the role of chance KS5.3 was significantly different between groups [E = 6.6(4.6-7.9) vs M = 5.3(2.9-7.2) vs A = 4.0(2.5-6.6), p 0.99]; [t4: E = 38.28 (35.63-41.19), M = 38.49 (35.47-42.13), A 39.72 (37.25-43.31), EvsA p = 0.0001, MvsA p = 0.02, EvsM p = 0.65]; [tb: E = 107.70 (102.20-114.30), M = 110.10 (103.60-116.80), A = 113.7 (106.80-122.70), EvsA p Limitations, reasons for caution All these findings have to be validated in a larger sample size. Furthermore, for the retrospective nature of this study, there were some confounding factors, such as protocol of stimulation, female age, and malefactor. This research did not consider the importance of every single kinetic parameter. Wider implications of the findings A further study is needed to verify if there is a correlation between morphology and ploidy status. This could clarify the difference in KS-5.3 between euploid and mosaic. In order to decrease age bias, we should enlarge the sample size to analyze a subgroup of patients with higher maternal age. Trial registration number not applicable

OBJECTIVE Studies have shown that prenatal exome sequencing (PES) improves diagnostic yield in cases of fetal structural malformation. We have retrospectively analysed PES cases from two of the largest fetal medicine centres in the UK to determine the impact of results on management of a pregnancy. DESIGN A retrospective review of clinical case notes. SETTING Two tertiary fetal medicine centres. POPULATION Pregnancies with fetal structural abnormalities referred to clinical genetics via a multidisciplinary team. METHODS We retrospectively reviewed the notes of all patients who had undergone PES. DNA samples were obtained via chorionic villus sampling or amniocentesis. Variants were filtered using patient-specific panels and interpreted using American College of Medical Genetics guidelines. RESULTS A molecular diagnosis was made in 42% (18/43) ongoing pregnancies; of this group, there was a significant management implication in 44% (8/18). A positive result contributed to the decision to terminate a pregnancy in 16% (7/43) of cases. A negative result had a significant impact on management in two cases by affirming the decision to continue pregnancy. CONCLUSIONS We demonstrate that the results of PES can inform pregnancy management. Challenges include variant interpretation with limited phenotype information. These results emphasise the importance of the MDT and collecting phenotype and variant data. As this testing is soon to be widely available, we should look to move beyond diagnostic yield as a measure of the value of PES. TWEETABLE ABSTRACT Prenatal exome sequencing can aid decision-making in pregnancy management; review ahead of routine implementation in NHS.

Infertility has been characterized as a disease by the World Health Organization (WHO) and reportedly affects about 10-12% of couples worldwide, while the incidence is even higher in Italy, at about 15%. The issue of iatrogenic infertility arising from treatments that can compromise an individual's reproductive capacity, it is necessary to inform patients of the possible damage on their future fertility and on the possibilities to preserve it. The complexities inherent in the various techniques and approaches aimed at preserving fertility should be expounded upon thoroughly to the patients, who should also receive proper psychological assistance and counseling, which ought to take into account the ethical distinctive challenges and the possible misgivings that may be caused in patients. Ovarian Tissue Cryopreservation (OTC) and ovarian tissue transplantation (OTT) can constitute a valuable part of the clinical armamentarium for preserving fertility, although the data are still inconclusive, particularly in over-36 patients. The multidisciplinary nature of the healthcare teams involved in such interventions is of paramount importance to optimize results.

O presente estudo trata da (in)constitucionalidade do crime de porte de drogas para consumo pessoal, tipificado no artigo 28 da Lei n.º 11.343/06. Por meio dele, demonstra-se que a criminalização de tal conduta, além dos já sabidos gravosos danos sociais causados, também se respalda em um bem jurídico incerto e abstrato, qual seja a Saúde Pública. Propõe-se assim uma análise crítica a respeito da utilização de bens jurídicos coletivos, como a saúde pública que o delito em tela busca tutelar, para contenção do poder punitivo. Por fim, aponta-se o reconhecimento, pelo Supremo Tribunal Federal da pertinência do tema no RE 635659/SP - que teve sua tramitação suspensa, sem previsão de retorno – tendo alguns ministros apresentado sua decisão a respeito do tema.

BackgroundDermatomyositis (DM) is a rare idiopathic inflammatory myopathy that can present with a variable spectrum of cutaneous and systemic manifestations1. Correlations between myositis-specific autoantibodies (MSAs) and disease phenotype have been documented in DM in particular in association with the development of interstitial lung disease (ILD). Ongoing studies focus on the potential role of MSAs in similarities of the pathophysiological mechanisms of COVID-19 associated ILD and that related to DM suggesting an intriguing cross talk between autoimmunity and COVID-192.ObjectivesTo explore clinical patterns including ILD and MSAs profile in DM patients from a population-based single-center study carried out in a Tertiary Referral Rheumatologic Clinic. SARS-CoV-2 infections and vaccination were also analysed.MethodsWe enrolled patients affected by DM classified according to 2017 EULAR/ACR criteria1 with a disease onset at ≥18 years referring to the Rheumatologic Clinic of Tor Vergata University Hospital in Rome (Italy). Clinical data were collected from medical records: gender, age of onset of symptoms and diagnosis, clinical features, auto-antibodies patterns (ANA, MSAs including anti-tRNA synthetase, -Jo1, -PL7, -EJ, - MDA5, -NXP2, SAE, Mi2, and myositis-associated antibodies comprising anti-PM/Scl, -Ro-52, -Ku, U1RNP), pattern of lung abnormalities at thoracic CT scans, and treatments. The prevalence of SARS-CoV-2 infection and vaccination profile were also investigated.ResultsAmong eligible cases (n=30), patients who completed the study (n=19) included almost entirely women (F=73.7%). The median age at disease onset was 57.4±12.4 yrs while the mean diagnostic delay resulted as 12±10 months. Skin manifestations and myalgia were the prevalent symptoms (79% and 63%, respectively) whereas dyspnea and cough occurred in a third of the cohort at DM onset. Besides the skin involvement, the decrease in pulmonary function was the main clinical manifestation at the first rheumatological referral (52.6% of cases) followed by joint pain (36.8%) and cardiovascular events (10.6%). ANA titer≥1:160 occurred in 79% of patients. All patients showed MSAs positivity with a similar distribution: a single case of double positivity was registered in a man with anti-MDA5 and -NXP2. The most common CT findings were ground-glass opacity and parenchymal band in a third of patients (32%). The entire cohort had undergone cycles of steroids from the onset of DM and during the follow-up, according to disease severity. The main used therapies were methotrexate (47%), intravenous immunoglobulin (42%) and mofetil micofenolate (31.6%). None of patients had SARS-CoV-2 infection (until December 2021). The 63% of the cohort received at least one dose of the anti- SARS-CoV-2 mRNA vaccine (BNT162b2), of which 10% had completed with the booster dose. No adverse reactions or post-vaccination DM flare were registered. A third of the cohort had not been vaccinated due to concomitant disease activity or therapies. No cases of post-COVID19 new-onset DM were diagnosed.ConclusionOur preliminary findings support the relevant impact of lung involvement in DM. The availability of MSAs can help to stratify patients with DM for outcome and risk of potential disease complications. The impact of MSAs on ILD associated or not to COVID-19 deserve further investigations in a larger DM cohort and for a longer post-COVID-19 pandemia follow-up time.References[1]Lundberg IE, et al. 2017 European League Against Rheumatism/American College of Rheumatology Classification Criteria for Adult and Juvenile Idiopathic Inflammatory Myopathies and Their Major Subgroups. Arthritis Rheumatol. 2017;69:2271-82.[2]Wang Y, et al. Similarities and differences between severe COVID-19 pneumonia and anti-MDA-5-positive dermatomyositis-associated rapidly progressive interstitial lung diseases: a challenge for the future. Ann Rheum Dis. 2020:annrheumdis-2020-218594.Disclosure of InterestsNone declared

Background. The interplay between female fertility and autoimmune diseases (AIDs) can involve HLA haplotypes and micronutrients. We analyzed the distribution of HLA-DQ2/-DQ8 in women with infertility or recurrent spontaneous abortion (RSA) and possible associations with AIDs and micronutrient status. Methods. Consecutive women (n = 187) with infertility and RSA, and controls (n = 350) were included. All women were genotyped for HLA-DQ2 (DQA1*0201, A1*05, and B1*02) and -DQ8 (DQA1*03 and DQB1*0302) alleles. Serum 25(OH)D, VB12, folate, and ferritin were evaluated. Results. DQA1*05/B1*02 and the occurrence of at least one DQ2 allele were more prevalent among RSA and infertile women than controls. Infertile women showed lower 25(OH)D and higher prevalence of AIDs than RSA women. In the multivariate analysis, DQA1*05/B1*02 was associated with a significantly higher risk of AIDs in infertile women, and DQA1*05 was independently associated with both 25(OH)D deficiency and AIDs. In RSA women, the presence of AIDs was associated with a significantly higher risk of 25(OH)D deficiency. Conclusion. Our findings showed, for the first time, a higher proportion of DQ2 alleles in infertile and RSA women as compared to controls. Predisposing DQ2 alleles are independent risk factors for AIDs and 25(OH)D deficiency in infertile women and could represent biomarkers for performing early detection of women requiring individually tailored management.

During the Covid-19 pandemic, many governments promoted the adoption and development of telework to reduce some of the consequences of the current health crisis on the economy and favor social distancing. The aim of this web-based cross-sectional study was to assess the consequences of the Covid-19 pandemic on job organization, exploring the effects of lockdown measures on the psychological distress and perceived well-being of workers experiencing telework.A web-based cross-sectional survey has been used to collect data. The participants answered the questionnaire from April 1 to April 30, 2020. The questionnaire consisted of three sections, which investigated: 1) demographic and occupational variables, 2) lifestyle and habits variables, 3) psychological distress and perceived well-being. The General Health Questionnaire (GHQ-12) has been used to evaluate psychological distress and the 5-item World Health Organization Well-Being Index (WHO-5) to explore subjective well-being.Psychological distress was associated with educational level, with habits, and with reporting poor well-being. Poor well-being was associated with a higher job demand during pandemic, lifestyle and habits variables, and psychological distress.This is one of the first studies exploring the consequences of the COVID-19 pandemic and lockdown measures on the perceived well-being and psychological distress of workers experiencing telework. It is mandatory to pay more and more attention to the mental health of teleworkers, considering the increasing diffusion and adoption of this type of work organization.

Background: Previous studies on oxaliplatin and fluoropyrimidines as adjuvant therapy in older patients with stage III colon cancer (CC) produced conflicting results. Patients and methods: We assessed the impact of age on time to tumour recurrence (TTR), disease-free survival (DFS), cancer-specific survival (CSS), and overall survival (OS) in 2360 patients with stage III CC (1667 aged

Since the day of its explosion, SN 1987A (SN87A) was closely monitored with the aim to study its evolution and to detect its central compact relic. The detection of neutrinos from the supernova strongly supports the formation of a neutron star (NS). However, the constant and fruitless search for this object has led to different hypotheses on its nature. Up to date, the detection in the ALMA data of a feature somehow compatible with the emission arising from a proto Pulsar Wind Nebula (PWN) is the only hint of the existence of such elusive compact object. Here we tackle this 33-years old issue by analyzing archived observations of SN87A performed Chandra and NuSTAR in different years. We firmly detect nonthermal emission in the $10-20$ kev energy band, due to synchrotron radiation. The possible physical mechanism powering such emission is twofold: diffusive shock acceleration (DSA) or emission arising from an absorbed PWN. By relating a state-of-the-art magneto-hydrodynamic simulation of SN87A to the actual data, we reconstruct the absorption pattern of the PWN embedded in the remnant and surrounded by cold ejecta. We found that, even though the DSA scenario cannot be firmly excluded, the most likely scenario that well explains the data is the PWN emission., Accepted for publication in ApJ Letters

According to the most popular model for the origin of cosmic rays (CRs), supernova remnants (SNRs) are the site where CRs are accelerated. Observations across the electromagnetic spectrum support this picture through the detection of non-thermal emission that is compatible with being synchrotron or inverse Compton radiation from high energy electrons, or pion decay due to proton-proton interactions. These observations of growing quantity and quality promise to unveil many aspects of CRs acceleration and require more and more accurate tools for their interpretation. Here, we show how multi-dimensional MHD models of SNRs, including the effects on shock dynamics due to back-reaction of accelerated CRs and the synthesis of non-thermal emission, turned out to be very useful to investigate the signatures of CRs acceleration and to put constraints on the acceleration mechanism of high energy particles. These models have been used to interpret accurately observations of SNRs in various bands (radio, X-ray and $\gamma$-ray) and to extract from them key information about CRs acceleration., Comment: 16 pages, 5 figures, invited review accepted for publication on New Astronomy

BackgroundPsoriatic Arthritis (PsA) is a chronic inflammatory disease, characterized by both articular and periarticular manifestations, usually associated with psoriasis. The identification of the correct therapy for patients is still a critical issue, but the use of biological drugs, such as TNFi (Tumor Necrosis Factor Inhibitors), modified the outcome of PsA patients even if there is great variability in the clinical efficacy. Since the response to drugs is a complex trait, the identification of genetic factors could help to define new genomic biomarkers for more effective and personalized therapy.ObjectivesThe aim of this study was to evaluate the potential role of polymorphisms in genes already known to be involved in PsA susceptibility (ERAP1, HCP5, IL10, MIR146, PSORS1C1, STAT4, TNFAIP3 and TRAF3IP2) as predictors of efficacy of treatment, in a cohort of Italian PsA patients, treated with first-line TNF-i, in particular with Etanercept (ETN) and Adalimumab (ADA).MethodsPolymorphisms were analyzed in a cohort of 163 patients with peripheral PsA. For each patient was estimated the Disease Activity in Psoriatic Arthritis (DAPsA) score. Genotyping was performed by allelic discrimination by TaqMan assay. The possible association between the selected SNPs and mean values of DAPsA differences, at 22 (ΔT22) and 54 (ΔT54) weeks from the beginning of the TNF-i treatment, were evaluated by T-test. A multivariate logistic regression analysis was used to evaluate the contribution of each genetic variant investigated in the TNF-i treatment response.ResultsWe have observed that TRAF3IP2 SNP was associated with TNF-i treatment response in PsA patients. In particular, the patients carrying variant alleles seem to respond better to treatment, both at 22 (P = 0.032) and 54 weeks (P = 0.019). Moreover, the variant allele of TRAF3IP2 SNP resulted associated with a better response of joints involvement. Indeed, the number of tender and swollen joints decrease more in patients carrying variant allele (P = 0.006 and P = 0.024, respectively). We also observed that PsA patients carrying IL10 variant allele decrease their mean DAPsA value less than patients with wild-type genotype only at 54 weeks of treatment (P = 0.031). Also, HCP5 polymorphism showed a difference of mean difference of DAPsA values between genotypes for both follow up, even if these difference does not reach a statistical significance (P = 0.068 and P = 0.086). The multivariate regression analysis was performed with a stepwise method and it confirmed the involvement of TRAF3IP2 (P = 0.016) and HCP5 (P = 0.035) polymorphisms in the TNF-i response after 22 weeks and of TRAF3IP2 (P = 0.007), IL10 (P = 0.022) and HCP5 (P = 0.036) polymorphisms after 54 weeks. The two final models explain about 6% and 11% of the variability in TNF-i treatment response at 22 and 54 weeks respectively.ConclusionOur results suggest that some polymorphisms in genes associated to PsA susceptibility could also play a role in TNFi treatment response and could give a contribution in the definition of a genetic profile associated with the response to anti-TNF drugs.Figure 1.Mean differences of DAPsA values in the genotypic classes for TRAF3IP2, IL10 and HCP5 SNPs. DAPsA = Disease Activity Index for PsA; Wt = wild-type genotype; Hz = heterozygous genotype; Homo var = homozygous variant genotype.Disclosure of InterestsNone declared

BackgroundJAK-inhibitors (JAK-i) represent an effective choice in achievement of therapeutic target in bio-naïve (bnaïve) and bDMARD-insufficient responders (bDMARD-IR) patients. However, oral glucocorticoids (OGC) are commonly used in clinical practice in combination with b/tsDMARDs in Rheumatoid and Psoriatic Arthritis (RA and PsA) patients in order to reach clinical remission.ObjectivesTo assess, in a real-life clinical setting, the reduction of OGC dose during JAK-i treatment in RA and PsA patients that were b-naïve or ≥1-bDMARD-IR or ≥2-bDMARDs-IR with different mechanisms of action.MethodsPatients with active RA or PsA treated with first JAKi were prospectively enrolled in a single center. Disease activity (DAS28-CRP or DAPSA), pain visual analogic scale (VAS-pain), general health (GH) and mean prednisone dosage (PDN dose) were collected at baseline and after 4, 8 and 12 months (T4, T8, T12) of treatment.Results89 patients with active arthritis (77 RA, 12 PsA) were treated with JAK-i (43 patients received Baricitinib, 41 Tofacitinib and 5 Upadacitinib), with all patients reaching T4, 65 patients T8 and 50 patients T12 (Table 1). 27% patients were b-naïve, 73% ≥1-bDMARD-IR and 34% ≥2-bDMARDs-IR. A mean OGC dose of 4.0 ± 4.6 (mg per day) was used and 39% of patients received JAK-i without csDMARDs. We observed a significant improvement of disease activity by DAS28-CRP or DAPSA, VAS-pain and GH at all time points in whole population (respectively pTable 1.Women75% (67)Age (years)60 ± 12Seropositive66% (51)Disease duration (months)132 ± 88DAS28 CRP4.0 ± 1.0DAPSA40.6 ± 19.7VAS-pain67.7 ± 15.8GH68.1 ± 15.2ConclusionJAK-i administration allows to reduce concomitant OGC regardless of line of b-DMARDs treatment. Chronic OGC may have detrimental bone, metabolic, cardiovascular and infective side effects; therefore JAK-i steroid-sparing effect may be beneficial for patients in long-term treatment.Disclosure of InterestsNone declared

BackgroundThe noninfectious uveitis (NIU) is the intraocular inflammation that can be the first or one of extra-articular manifestations of systemic inflammatory rheumatic diseases mainly including spondyloarthritis (SpA), Behcet’s disease (BD) and juvenile idiopathic arthritis (JIA)1. Rheumatologists are often asked to help in diagnostic assessment and relatively targeted treatment of particular subsets of NIU2.ObjectivesTo explore patterns and treatments of NIU from a population-based single-center study carried out in a Tertiary Referral Rheumatologic Clinic.MethodsSelection criteria of this cross-sectional descriptive study consisted of having a diagnosis of NIU in an age of onset ≥16 years old regardless of its etiology among patients who were admitted (February 2018-December 2021) to Rheumatologic Clinic of Tor Vergata University Hospital (Rome, Italy). Clinical data were collected from medical records: gender, age of onset and admission, recurrence and anatomic patterns, HLA-B27 susceptibility, associated rheumatologic diagnosis and treatments were investigated.ResultsWe included 100 patients with 58% women. Median age at NIU onset was 39.6±15 years whereas patients were 44±14 years old at the first referral, without gender-difference. NIU represented the main reason of referral in 22% of cases. Anterior uveitis occurred in 73% of patients and posterior in 25%; intermediate (IU) and panuveitis (PanU) were isolated cases. The prevalent course was acute (57%) followed by recurrent (31%) and chronic (12%); both eyes were involved in 39 patients. Almost half of NIU was associated with SpA including IBD-SpA (20%), ankylosing spondylitis (AS, 18%), and Psoriatic Arthritis (12%). A diagnosis of BD was reported in 14% of NIU while Rheumatoid Arthritis and other systemic autoimmune diseases occurred in 11% and 12%, respectively. Idiopathic NIU and JIA-NIU constituted the lowest prevalence (8% and 5%, respectively). A higher prevalence of BD-NIU and AS-NIU resulted in males than females (p+: a higher percentage of unilateral (p=0.09) and acute course (p=0.02) occurred in B27+ than B27-. AS was prevalent in B27+ NIU than B27- (p- NIU than B27+ (p=0.09 and p=0.04 respectively). The only two cases of IU and PanU were both idiopathic B27- NIU. At the onset of NIU, most patients were not on systemic treatment (68%): remaining cases were on cDMARDs (22%) and bDMARDs (10%). During rheumatologic follow-up, 80% of patients changed therapies: cDMARDs were added in 43.7% patients while bDMARDs were started in 40%. Systemic steroids were added in the remaining 16.3% of patients. At the latest follow-up (follow-up-time 33±28 months), 86% of patients had achieved remission of NIU while 14% had recurrence of active uveitis.ConclusionFindings from this population-based study describe a representative estimate of extent and patterns of NIU in an Italian adult cohort from a single Rheumatologic Clinic and document that Rheumatologic referral might dramatically impact treatment strategies in NIU.References[1]Hysa, E., et al. (2021). Immunopathophysiology and clinical impact of uveitis in inflammatory rheumatic diseases: An update. European journal of clinical investigation, 51(8), e13572. doi.org/10.1111/eci.13572.[2]Rosenbaum, J. T., et al. (2019). New observations and emerging ideas in diagnosis and management of non-infectious uveitis: A review. Seminars in arthritis and rheumatism, 49(3), 438–445. doi: 10.1016/j.semarthrit.2019.06.004.Disclosure of InterestsNone declared

Background The anconeus is a small muscle located on the posterior elbow originating on the lateral epicondyle and inserting onto the proximal-lateral ulna that functions as an elbow extensor as well as dynamic stabilizer. The blood supply is tri-fold: medial/middle collateral artery (MCA), recurrent posterior interosseous artery (RPIA), and less commonly found, the posterior branch of the radial collateral artery. The anconeus has become a popular option for local soft tissue coverage about the elbow (distal triceps, olecranon, proximal forearm). The average defect size for consideration of local anconeus flap coverage is 5–7cm2. The aim of the study was to determine safe dissection parameters of the anconeus as well as map arterial pedicles to achieve successful local harvest of the muscle without devascularization. Materials and Methods 8 fresh frozen cadaveric arms (all male, average age 63 years – 4 left arms, 4 right arms) from scapula to fingertip were obtained. First, the radial, ulnar and axillary arteries were dissected and isolated. The radial and ulnar arteries were transected. 100cc normal saline was injected through the axillary artery, sequentially clamping the radial followed by the ulnar artery so that adequate flow could be seen through all vessels. 100cc mixture of Biodür and hardener (10:1) was mixed and injected into the axillary artery. We first allowed free flow through both the ulnar and radial vessels followed by clamping of these vessels. This allowed the pressure to build up and fill the smaller vessels in the arms. After injection, the axillary artery was then clamped and the specimens were left to harden for 24–48 h. After hardening, dissection was performed by making a curvilinear incision centred over the lateral epicondyle. The anconeus was identified and the interval between the anconeus and ECU was then confirmed. Measurements of the anconeus muscle were taken. Blunt dissection was carried between anconeus and ECU until the RPIA was identified and protected. We isolated the MCA by dissecting proximally. This was found to run with the nerve to the anconeus. Once this vessel had been protected, the muscle reflected from distal to proximal staying along its ulnar border. The branches of the RPIA were ligated and the dissection was continued proximally. Measurements of the distances of the RPIA, MCA were taken. Results The average distance of olecranon to muscle tip was 95.0mm. The average distance of lateral epicondyle (LE) to muscle tip was 90.8mm. The average distance of LE to olecranon was 49.8mm. The average location of the RPIA was 63.mm when measuring LE to vessel, 68.3mm when measuring olecranon to vessel, 18.3mm when measuring RPIA to muscle tip. The average RPIA diameter was 1.1mm and length was 36.4mm from the initial branching of the posterior interosseous artery. The average MCA diameter was 0.7mm. The posterior branch of the radial collateral artery was only found in 3/8 specimens. The RPIA and MCA were constant in all specimens. Dissection was safely carried to the border of the LE and olecranon without disruption of the MCA. CONCLUSIONS Our conclusions determined that if dissection of the anconeus is undertaken, the RPIA remains constant between the interval of the ECU as well as anconeus at an average distance of 18.3mm from the tip of the muscle measuring proximally; moreover, the MCA was constant in all specimens found directly between the LE and olecranon always running with the nerve to the anconeus. When dissecting and mobilizing to ensure preservation of the MCA, dissection should be taken from distal to proximal as well as dissecting along the ulnar border of the anconeus. Proximal dissection can be taken as proximal as the border of the LE and olecranon as that did not disrupt MCA blood supply.

Introduction: We report a case of a young female patient, previously affected by psoriatic arthritis, and treated with adalimumab, who developed a chronic spontaneous urticaria and started a concomitant therapy with omalizumab. Methods & results: A 50% reduction of the Dermatology Life Quality Index (from 7 at baseline to 4 in weeks 12 and 24) and a complete reset of the Urticaria Activity Score for 7 days (from 27 at baseline to 0 in weeks 12 and 24) were recorded. During all treatment with omalizumab, administering of adalimumab was continued. Due to complete control of urticaria symptoms, the patient stopped treatment with omalizumab after 24 weeks. Conclusion: The combination of adalimumab and omalizumab could offer a favorable efficacy and safety profile. The synergistic action of the two biological drugs in reducing systemic inflammation could be responsible for a shorter time to obtain clinical response.

Child overweight and obesity prevalence has risen substantially in most high-income countries. The prevention of childhood overweight and obesity is a major public health issue. Childhood obesity leads to an increased risk of both physical and mental health consequences,. The aim of this study was to investigate the gender differences in BMI z-score, eating habits, life style and healthy behaviors in children.With an approach so-called "cluster" method we selected third classes of primary schools. The study was conducted from September 2016 and May 2017 during a school year. Information was collected through a questionnaire filled in by the children with the help of their parents. The biometric data relating to height in meters and weight in kilograms was obtained through the questionnaire.A total of 1122 children were included in the current study. 33.9% of boys being overweight compared with 27.8% of girls and 19.1% of boys being obese compared with 12.5% of girls (p0.001). There were significant differences between boys and girls for physical activity (p=0.004), sedentary behaviors (p0.001), eating habits (p=0.004).In this study, gender differences were analyzed with respect to BMI z-score, eating habits, life style and healthy behaviors in children between 9 and 11 years old. The results of the study confirm the differences that the scientific literature described. Between boys and girls there are different habits that on the one hand can determine differences in the quality of life and future health and on the other hand can be the key to implementing effective and targeted prevention interventions.

To recover a threatened or endangered species, numerous local government jurisdictions are usually involved in habitat mitigation and conservation planning actions for evaluating impacts to habitat. In the USA local governments make official land use decisions. A social-ecological case study of multiple counties is presented tabulating the relative "contribution to recovery" by each county for giant garter snake (GGS; Thamnophis gigas), a federally and state-listed threatened California endemic watersnake species that is reliant on rice agriculture. The entire geographic range of the GGS is examined in relation to multiple county boundaries, recovery unit boundaries, federal habitat conservation plan (HCP) coverage, California natural community conservation plan (NCCP) coverage, and piecemeal mitigation (areas lacking formal conservation plans). Results indicate that of the 22 counties that cover the range of the GGS, nine counties have HCPs that cover the species in 38% of the range and of those nine HCPs six have NCCPs covering 14% of the range. Thus, more than half of the range (62%) mitigates for impacts to the GGS in a project-by-project (piecemeal) manner with no HCP, while 24% of the range has a population jeopardy standard covered by HCPs and 14% has a population recovery standard covered by NCCPs. However, four of the nine recovery units are substantially covered by HCP or NCCP conservation plans (~65-81%), while the remaining five units have far less coverage (~1-36%). Ninety-nine percent of all known GGS occurrences were found in Sutter, Sacramento, Yolo, Colusa, Butte, Merced, Glenn, San Joaquin, Fresno, Solano, and Kern counties (n = 85, 55, 51, 44, 36, 27, 17, 9, 9, 4, 4, respectively). These 11 counties will play an important role toward contributing to recovery of the GGS. In theory, the variation in different conservation standards over a species' range could have significant implications for its ultimate recovery potential.

Bullying is a serious and growing problem affecting a significant proportion of healthcare professionals, a professional category exposed to work-related stress. Workplace bullying has been defined as a set of negative behaviours consisting in harassment, offense or negative influence on work that are directed to the members of the organization and that occur regularly and repeatedly over a period, becoming part of the context of work.We performed a cross-sectional study using the HSE questionnaire and defining the sample size considering the number of healthcare workers of a big hospital and then calculating it with EpiInfo™ software. 191 people have been enrolled.The study was divided into three steps. The first one to identify, among the workers, those who were exposed to bullying at work and those who were not. The second one has been aimed at assessing the presence of work-related stress through the administration of the HSE questionnaire. The third step has been aimed at performing the statistical analysis of the data. For each single domain explored by the questionnaire the score obtained was treated as a linear variable and the median and interquartile range (IQR) was calculated. After, a non-parametric analysis (Wilcoxon rank-sum test) was performed in order to define the statistical significance of the observed differences.All the 191 questionnaires were self-administered by the Health Care Workers under study and correctly filled in without any multiple or missing responses. Considering the scores obtained to question n. 21, that investigates "bullying at work", we obtained two groups: High-Exposure Group (total, males and females), and Low-Exposure Group (total, males and females). In the High-Exposure Group, two critical domains were found: Demands and Control (total, male and female samples). The differences with the Low-Exposure Group were statistically significant. In the Low-Exposure Group the critical domain was Manager Support (total and female samples). The differences with the High Exposure Group were not statistically significant.This study aimed to show how the exposure to bullying can influence the perception of psychosocial risks. It seems that the workers most exposed to bullying also have worse scores on the HSE questionnaire, particularly for two domains: Demands and Control. That is consistent with the most recent scientific literature.

Spectral analysis of X-ray emission from ejecta in supernova remnants (SNRs) is hampered by the low spectral resolution of CCD cameras, which creates a degeneracy between the best-fit values of abundances and emission measure. The combined contribution of shocked ambient medium and ejecta to the X-ray emission complicates the determination of the ejecta mass and chemical composition, leading to big uncertainties in mass estimates and it can introduce a bias in the comparison between the observed ejecta composition and the yields predicted by explosive nucleosynthesis. We explore the capabilities of present and future spectral instruments with the aim of identifying a spectral feature which may allow us to discriminate between metal-rich and pure-metal plasmas in X-ray spectra of SNRs. We studied the behavior of the most common X-ray emission processes of an optically thin plasma in the high-abundance regime. We investigated spectral features of bremsstrahlung, radiative recombination continua (RRC) and line emission, by exploring a wide range of chemical abundances, temperatures and ionization parameters. We synthesized X-ray spectra from a 3D hydrodynamic (HD) simulation of Cas A, by using the response matrix from the Chandra/ACIS-S CCD detector and that of the XRISM/Resolve X-ray calorimeter. We found that a bright RRC shows up when the plasma is made of pure-metal ejecta, and a high spectral resolution is needed to identify this ejecta signature. We verified the applicability of our novel diagnostic tool and we propose a promising target for the future detection of such spectral feature: the southeastern Fe-rich clump of Cas A. While there is no way to unambiguously reveal pure-metal ejecta emission with CCD detectors, X-ray calorimeters will be able to pinpoint the presence of pure-metal RRC and to recover correctly absolute mass and the chemical composition of the ejecta., 13 pages, 12 figures, accepted for publication in A&A

The morphology and the distribution of material observed in SNRs reflect the interaction of the SN blast wave with the ambient environment, the physical processes associated with the SN explosion and the internal structure of the progenitor star. IC 443 is a MM SNR located in a quite complex environment: it interacts with a molecular cloud in the NW and SE areas and with an atomic cloud in the NE. In this work we aim at investigating the origin of the complex morphology and multi-thermal X-ray emission observed in SNR IC 443, through the study of the effect of the inhomogeneous ambient medium in shaping its observed structure, and the exploration of the main parameters characterizing the remnant. We developed a 3D HD model for IC 443, which describes the interaction of the SNR with the environment, parametrized in agreement with the results of the multi-wavelength data analysis. We performed an ample exploration of the parameter space describing the initial blast wave and the environment, and the surrounding clouds. From the simulations, we synthesized the X-ray emission maps and spectra and compared them with actual X-ray data collected by XMM-Newton. Our model explains the origin of the complex X-ray morphology of SNR IC 443 in a natural way, being able to reproduce, for the first time, most of the observed features, including the centrally-peaked X-ray morphology (characteristic of MM SNRs) when considering the origin of the explosion at the position where the PWN CXOU J061705.3+222127 was at the time of the explosion. In the model which best reproduces the observations, the mass of the ejecta and the energy of the explosion are $\sim 7 M_\odot$ and $\sim10^{51}$ erg, respectively. From the exploration of the parameter space, we found that the density of the clouds is $n>300$ cm$^{-3}$ and that the age of SNR IC 443 is $\sim8000$ yr., 16 pages, 12 figures. Accepted for publication in Astronomy and Astrophysics