Identification of homozygous deletion in ACAN and other candidate variants in familial classical Hodgkin lymphoma by exome sequencing

Tutkimuksessamme tarkastelimme Lähi-idästä lähtöisin olevaa perhettä, jossa kolmella viidestä lapsesta on todettu nuorellä iällä klassinen Hodgkinin lymfooma (cHL). Perinnöllinen alttius cHL:lle tunnetaan huonosti, eikä taudille mahdollisesti altistavia geenimuutoksia ole aiemmin raportoitui kuin yksi kappale. Geenimuutosten selvittämiseksi eksomisekvensoimme kolmen sairastuneen lapsen verinäytteestä eristetyn DNA:n ja poimimme joukosta kaikkien kolmen jakamat muutokset. Suodatimme lasten jakamien DNA-muutosten joukosta pois omissa vertailujoukoissamme ja useissa julkisissa tietokannoissa esiintyvät geneettiset muutokset ja arvioimme jäljellejääneiden muutosten haitallisuutta kahdella laskennallisella priorisaatioalgoritmilla. Näin saimme järjestettyä jäljelle jääneet 35 jaettua muutosta laskennalliseen haitallisuusjärjestykseen. Jaetuista muutoksista merkittävimmäksi nousi ACAN-geenissä oleva homotsygoottinen 57 emäksen pituinen deleetio c.2836_2892del, jota ei ole aiemmin liitytty cHL-fenotyyppiin

Polynomially Over-Parameterized Convolutional Neural Networks Contain Structured Strong Winning Lottery Tickets

The Strong Lottery Ticket Hypothesis (SLTH) states that randomly-initialised neural networks likely contain subnetworks that perform well without any training. Although unstructured pruning has been extensively studied in this context, its structured counterpart, which can deliver significant computational and memory efficiency gains, has been largely unexplored. One of the main reasons for this gap is the limitations of the underlying mathematical tools used in formal analyses of the SLTH. In this paper, we overcome these limitations: we leverage recent advances in the multidimensional generalisation of the Random Subset-Sum Problem and obtain a variant that admits the stochastic dependencies that arise when addressing structured pruning in the SLTH. We apply this result to prove, for a wide class of random Convolutional Neural Networks, the existence of structured subnetworks that can approximate any sufficiently smaller network. This result provides the first sub-exponential bound around the SLTH for structured pruning, opening up new avenues for further research on the hypothesis and contributing to the understanding of the role of over-parameterization in deep learning.Comment: To be published in the 37th Conference on Neural Information Processing Systems (NeurIPS 2023

Multi-model study of mercury dispersion in the atmosphere : Atmospheric processes and model evaluation

Current understanding of mercury (Hg) behavior in the atmosphere contains significant gaps. Some key characteristics of Hg processes, including anthropogenic and geogenic emissions, atmospheric chemistry, and air-surface exchange, are still poorly known. This study provides a complex analysis of processes governing Hg fate in the atmosphere involving both measured data from ground-based sites and simulation results from chemical transport models. A variety of long-term measurements of gaseous elemental Hg (GEM) and reactive Hg (RM) concentration as well as Hg wet deposition flux have been compiled from different global and regional monitoring networks. Four contemporary global-scale transport models for Hg were used, both in their state-of-the-art configurations and for a number of numerical experiments to evaluate particular processes. Results of the model simulations were evaluated against measurements. As follows from the analysis, the interhemispheric GEM gradient is largely formed by the prevailing spatial distribution of anthropogenic emissions in the Northern Hemisphere. The contributions of natural and secondary emissions enhance the south-to-north gradient, but their effect is less significant. Atmospheric chemistry has a limited effect on the spatial distribution and temporal variation of GEM concentration in surface air. In contrast, RM air concentration and wet deposition are largely defined by oxidation chemistry. The Br oxidation mechanism can reproduce successfully the observed seasonal variation of the RM=GEM ratio in the near-surface layer, but it predicts a wet deposition maximum in spring instead of in summer as observed at monitoring sites in North America and Europe. Model runs with OH chemistry correctly simulate both the periods of maximum and minimum values and the amplitude of observed seasonal variation but shift the maximum RM=GEM ratios from spring to summer. O3 chemistry does not predict significant seasonal variation of Hg oxidation. Hence, the performance of the Hg oxidation mechanisms under study differs in the extent to which they can reproduce the various observed parameters. This variation implies possibility of more complex chemistry and multiple Hg oxidation pathways occurring concurrently in various parts of the atmosphere

A Chemical Transport Model Emulator for the Interactive Evaluation of Mercury Emission Reduction Scenarios

Implementation of the Minamata Convention on Mercury requires all parties to "control, and where feasible, reduce" mercury (Hg) emissions from a convention-specified set of sources. However, the convention does not specify the extent of the measures to be adopted, which may only be analysed by decision-makers using modelled scenarios. Currently, the numerical models available to study the Hg atmospheric cycle require significant expertise and high-end hardware, with results which are generally available on a time frame of days to weeks. In this work we present HERMES, a statistical emulator built on the output of a global Chemical Transport Model (CTM) for Hg (ECHMERIT), to simulate changes in anthropogenic Hg (Hganthr) deposition fluxes in a source-receptor framework, due to perturbations to Hganthr emissions and the associated statistical significance of the changes. The HERMES emulator enables stakeholders to evaluate the implementation of different Hganthr emission scenarios in an interactive and real-time manner, simulating the application of the different Best Available Technologies. HERMES provides the scientific soundness of a full CTM numerical framework in an interactive and user-friendly spreadsheet, without the necessity for specific training or formation and is a first step towards a more comprehensive, and integrated, decision support system to aid decision-makers in the implementation of the Minamata Convention

An Assessment of Stratospheric Intrusions in Italian Mountain Regions Using STEFLUX

The Mediterranean basin is considered a global hot-spot region for climate change and air quality, especially concerning summer-time ozone (O3). Previous investigations indicated that the Mediterranean basin is a preferred region for stratosphere-to-troposphere exchange (STE) and deep stratospheric intrusion (SI) events. The Lagrangian tool STEFLUX, based on a STE climatology that uses the ERA Interim data, was hereby used to diagnose the occurrence of deep SI events in four mountain regions over the Italian peninsula, spanning from the Alpine region to the southern Apennines. By using near-surface O3 and relative humidity (RH) observations at three high-mountain observatories, we investigated the performance of STEFLUX in detecting deep SI events. Both experimental and STEFLUX detections agreed in describing the seasonal cycle of SI occurrence. Moreover, STEFLUX showed skills in detecting "long-lasting" SI events, especially in the Alps and in the northern Apennines. By using STEFLUX, we found positive tendencies in the SI occurrence during 1979–2017. However, in contrast to similar studies carried out in the Alpine region, the negative long-term (1996–2016) trend of O3 in the northern Apennines did not appear to be related to the SI's variability

Integration and optimization of the after-treatments systems to reduce the acoustic footprint of the ships

Exhaust Gas Cleaning Systems (EGCS) such as scrubbers are mandatory and extensively used to abate SOx in exhaust gases when high sulphur content fuel oil is employed in the marine engine in order to comply with international ship emission regulations, both in new and existing ships. Currently, about 13% of bulker, container, and tanker ships have a scrubber installed, despite the fact that their installation on board is challenging due to their large dimensions to be fitted into the funnel and the complexity of the system, since the exhaust line must control both the chemical and acoustic emissions. In the presented work a combined FEM, CFD simulations and GA optimization methodology aimed at the integration of the abatement system, while optimizing the acoustic properties, is developed. The methodology is first assessed on an industrially-relevant scenario that involves the use of a Genset mock-up equipped with a reference Diesel Oxidation Catalyst (DOC) and a scrubber for the abatement of both NOx and SOx, showing that acoustic performances of the DOC are reliably modelled by the FEM-CFD methodology, which has a significantly reduced computational cost as compared to conventional CFD modelling of acoustic properties. The GA optimization is carried out to improve the DOC acoustic properties showing that it is possible to confer the silencing effect to the after-treatment systems, thus eliminating the traditional silencers from the exhaust line. This leads to a compact exhaust line that integrates the EGCS while maintaining efficient both the chemical pollution abatement capability, and silencing effects to guarantee full compliance (i.e., acoustic and chemical) with the international regulations

HLA Associations and Risk of Posttransplant Lymphoproliferative Disorder in a Danish Population-Based Cohort

Granični poremećaj ličnosti je učestali psihički poremećaj koji se manifestira kroz simptome afektivne nestabilnosti, impulzivnog i nekontroliranog ponašanja, poremećaj identiteta, nestabilne interpersonalne odnose i moguće pogreške u testiranju realiteta uslijed kojih osoba može imati značajnih poteškoća u osobnom, roditeljskom, obiteljskom, socijalnom i radnom funkcioniranju. Svrha ovog istraživanja je dobiti uvid u iskustva rada stručnih djelatnika Odjela za zaštitu djece, obitelji i braka pri centru za socijalnu skrb, a ciljevi istraživanju su dobiti uvid u prepoznavanje simptoma graničnog poremećaja ličnosti , teškoće i potrebe stručnih djelatnika Odjela za zaštitu djece, obitelji i braka. Kvalitativno istraživanje provedeno je metodom polustrukturiranog intervjua s 12 stručnjaka zaposlenih na Odjelu za zaštitu djece, obitelji i braka pri centrima za socijalnu skrb na području grada Zagreba i Zagrebačke županije. U obradi podataka korištena je tematska analiza. Rezultati istraživanja pokazuju da stručnjaci prepoznaju različite simptome afektivne nestabilnost, impulzivnog i nekontroliranog ponašanja, smetnji identiteta, nestabilnih i intenzivnih interpersonalnih odnosa te teškoća testiranja realiteta. Simptomi graničnog poremećaja ličnosti roditelja najčešće dolaze do izražaja u situacijama prekida bračne ili izvanbračne zajednice koji često imaju obilježja visokonfliktnih razvoda, tijekom postupaka odlučivanja o roditeljskoj skrbi, obiteljskog i partnerskog nasilja te zlostavljanja i zanemarivanja djece zbog čega stručnjaci poduzimaju različite psihosocijalne intervencije i mjere obiteljsko pravne zaštite. Prema rezultatima istraživanja teškoće stručnjaka tijekom rada s roditeljima s dijagnozom i/ili simptomima graničnog poremećaja ličnosti proizlaze iz neposrednog rada s roditeljima, organizacije i uvjeta rada u centrima za socijalnu skrb te suradnje s drugim sustavima. Roditelji sa simptomima ovog poremećaja ličnosti prepoznati su kao nedobrovoljni korisnici skloni manipulaciji djetetom, drugim roditeljem, stručnjacima, policijom, pravosudnim, zdravstvenim i socijalnim sustavom. Rad stručnjaka otežavaju i dodatne teškoće kao što su preopterećenost količinom posla, nedovoljan broj stručnih djelatnika, neadekvatni prostorni uvjeti rada u centrima za socijalnu skrb i otežana suradanja s drugim sustavima. Nadalje, stručnjaci izvještavaju o izloženosti visokoj razini profesionalnog stresa i doživljenim simptomima sagorijevanja. U skladu s iskazanim teškoćama, stručnjaci ukazuju na nužnost unaprjeđenja suradnje s drugim sustavima, posebice s pravosudnim, zdravstvenim i obrazovnim sustavom, povećanja broja zaposlenih stručnih djelatnika, zapošljavanje psihijatra u centre za socijalnu skrb, uključenost u redovite edukacije i supervizije. Nadalje, stručnjaci iskazuju potrebu za dodatnim ovlastima kao što su mogućnost obveznog upućivanja korisnika na liječenje i konstatiranja nedostupnosti intervencijama socijalne službe.Borderline personality disorder is a frequent psychiatric disorder which manifests itself through several symptoms: affective instability, impulsive and disinhibited behaviour, disturbed sense of identity, unstable interpersonal relationships and possible stress-related reduction of contact with reality. The afflicted person may have significant difficulties in personal, parental, familial, social and work functioning. The purpose of this research was to gain insight into experiences of experts working in the Department for protection of children, family and marriage of the Social Welfare Centre. Qualitative research has been conducted using semi-structured interviews with 12 experts working in the Department for protection of children, family and marriage of Social Welfare Centres located in Zagreb and Zagreb County. Collected data was analysed using thematic analysis. Results have demonstrated that experts recognize various symptoms of affective instability, impulsive and disinhibited behaviour, identity disturbances, unstable and intense interpersonal relationships and reduction of contact with reality. Symptoms of parental borderline personality disorder most frequently appear after a divorce or separation which often have characteristics of high-conflict divorce, during procedures related to child custody, familial and domestic violence, as well as child abuse and neglect, forcing experts to do various psychosocial interventions and implement measures related to protection of the family. According to results of this research difficulties expressed by experts working eith parents with a diagnosis and/or symptoms of borderline personality disorder are the result of direct work with the parents, organisation and work conditions in Social Welfare Centres and cooperation with other systems. Symptomatic parents are recognized as involuntary clients prone to manipulation of children, other parent, experts, the police, the justice system, healthcare system and social system. There are additional difficulties for experts working with these parents, such as work overload, insufficient number of experts, inadequate working space in Social Welfare Centres and difficulties cooperating with other systems. Experts also report being exposed to high level of professional stress and experiencing symptoms of burn-out. Consistently with these difficulties, experts reported needing to improve cooperation with other systems, especially with the justice, healthcare and education systems, increase the number of hired experts, hire psychiatrists in Social Welfare Centres and taking part regularly in educations and supervisions. Experts also reported needing additional authorities, such as the possibility of mandatory reference to treatment of clients and the possibility of establishing the unavailability of social services interventions

Low Absolute Lymphocyte Counts in the Peripheral Blood Predict Inferior Survival and Improve the International Prognostic Index in Testicular Diffuse Large B-Cell Lymphoma

Low absolute lymphocyte counts (ALC) and high absolute monocyte counts (AMC) are associated with poor survival in patients with diffuse large B-cell lymphoma (DLBCL). We studied the prognostic impact of the ALC and AMC in patients with testicular DLBCL (T-DLBCL). T-DLBCL patients were searched using Southern Finland University Hospital databases and the Danish lymphoma registry. The progression free survival (PFS) and overall survival (OS) were assessed using Kaplan-Meier and Cox proportional hazards methods. We identified 178 T-DLBCL patients, of whom 78 (44%) had a low ALC at diagnosis. The ALC did not correlate with survival in the whole cohort. However, among the patients treated with rituximab (R) containing regimen, a pre-therapeutic low ALC was associated with an increased risk of progression (HR 1.976, 95% CI 1.267-3.086,p= 0.003). Conversely, intravenous (iv) CNS directed chemotherapy translated to favorable outcome. In multivariate analyses, the advantage of an iv CNS directed chemotherapy was sustained (PFS, HR 0.364, 95% CI 0.175-0.757,p= 0.007). The benefit of R and intravenous CNS directed chemotherapy was observed only in non-lymphopenic patients. The AMC did not correlate with survival. A low ALC is an adverse prognostic factor in patients with T-DLBCL. Alternative treatment options for lymphopenic patients are needed.Peer reviewe