Distinguishing cause from effect - many deficits associated with developmental dyslexia may be a consequence of reduced and suboptimal reading experience

The cause of developmental dyslexia is still unknown despite decades of intense research. Many causal explanations have been proposed, based on the range of impairments displayed by affected individuals. Here we draw attention to the fact that many of these impairments are also shown by illiterate individuals who have not received any or very little reading instruction. We suggest that this fact may not be coincidental and that the performance differences of both illiterates and individuals with dyslexia compared to literate controls are, to a substantial extent, secondary consequences of either reduced or suboptimal reading experience or a combination of both. The search for the primary causes of reading impairments will make progress if the consequences of quantitative and qualitative differences in reading experience are better taken into account and not mistaken for the causes of reading disorders. We close by providing four recommendations for future research

Carbon Ion irradiation in the treatment of grossly incomplete or unresectable malignant peripheral nerve sheaths tumors: acute toxicity and preliminary outcome

Background: To report our early experience with carbon ion irradiation in the treatment of gross residual or unresectable malignant peripheral nerve sheath tumors (MPNST). Methods: We retrospectively analysed 11 patients (pts) with MPNST, who have been treated with carbon ion irradiation (C12) at our institution between 2010 and 2013. All pts had measurable gross disease at the initiation of radiation treatment. Median age was 47 years (29-79). Tumors were mainly located in the pelvic/sacral (5 pts) and sinunasal/orbital region (5 pts). 5 pts presented already in recurrent situation, 3 pts had been previously irradiated, and in 3 pts MPNST were neurofibromatosis type 1 (NF1) associated. Median cumulative dose was 60 GyE. Treatment was carried out either as a combination of IMRT plus C12 boost (4 pts) or C12 only (7 pts). Results: Median follow-up was 17 months (3-31 months). We observed 3 local progressions, translating into estimated 1- and 2-year local control rates of 65%. One patient developed distant failure, resulting in estimated 1- and 2-year PFS rates of 56%. Two patients have died, therefore the estimated 1- and 2-year OS rates are 75%. Acute radiation related toxicities were generally mild, no grade 3 side effects were observed. Severe late toxicity (grade 3) was scored in 2 patients (trismus, wound healing delays). Conclusion: Carbon ion irradiation yields very promising short term local control and overall survival rates with low morbidity in patients suffering from gross residual or unresectable malignant peripheral nerve sheath tumors and should be further investigated in a prospective trial

Prospects for a New Global Convention of the Elimination of Violence against Women

The World Health Organization (WHO) published a pioneering study in 2013 to measure global and regional estimates of violence against women, and found that 1 in 3 women has been a victim of physical and/or sexual violence because of her gender in her lifetime, with significant majority of these women falling victim to their intimate partner. For the purpose of this study, we use a broader definition: “any act of gender-based violence that results in, or is likely to result in, physical, sexual or psychological harm or suffering to women, including threats of such acts, coercion or arbitrary deprivation of liberty, whether occurring in public or in private life.” This paper will address the need and feasibility for a new international and legally binding treaty specifically on the elimination of all forms of violence against women

Generalizability and reach of a randomized controlled trial to improve oral health among home care recipients: comparing participants and nonparticipants at baseline and during follow-up

Background The generalizability of randomized controlled trials (RCTs) with a low response can be limited by systematic differences between participants and nonparticipants. This participation bias, however, is rarely investigated because data on nonparticipants is usually not available. The purpose of this article is to compare all participants and nonparticipants of a RCT to improve oral health among home care recipients at baseline and during follow-up using claims data. Methods Seven German statutory health and long-term care insurance funds invited 9656 home care recipients to participate in the RCT MundPflege. Claims data for all participants (n = 527, 5.5% response) and nonparticipants (n = 9129) were analyzed. Associations between trial participation and sex, age, care dependency, number of Elixhauser diseases, and dementia, as well as nursing, medical, and dental care utilization at baseline, were investigated using multivariable logistic regression. Associations between trial participation and the probability of (a) moving into a nursing home, (b) being hospitalized, and (c) death during 1 year of follow-up were examined via Cox proportional hazards regressions, controlling for baseline variables. Results At baseline, trial participation was positively associated with male sex (odds ratio 1.29 [95% confidence interval 1.08–1.54]), high (vs. low 1.46 [1.15–1.86]) care dependency, receiving occasional in-kind benefits to relieve caring relatives (1.45 [1.15–1.84]), having a referral by a general practitioner to a medical specialist (1.62 [1.21–2.18]), and dental care utilization (2.02 [1.67–2.45]). It was negatively associated with being 75–84 (vs. < 60 0.67 [0.50–0.90]) and 85 + (0.50 [0.37–0.69]) years old. For morbidity, hospitalizations, and formal, respite, short-term, and day or night care, no associations were found. During follow-up, participants were less likely to move into a nursing home than nonparticipants (hazard ratio 0.50 [0.32–0.79]). For hospitalizations and mortality, no associations were found. Conclusions For half of the comparisons, differences between participants and nonparticipants were observed. The RCT’s generalizability is limited, but to a smaller extent than one would expect because of the low response. Routine data provide a valuable source for investigating potential differences between trial participants and nonparticipants, which might be used by future RCTs to evaluate the generalizability of their findings. Trial registrati German Clinical Trials Register DRKS00013517. Retrospectively registered on June 11, 2018

Faktablad – Resultat från övervakningen av kustfisk

• Provfisket i Barsebäck har utförts med ryssjor i augusti varje år sedan 1977, förutom 2020. Från och med 2021 utförs fisket med reviderat provfiskemetod. Fisket var ursprungligen en del av kontrollprogrammet för kärnkraftverket. I detta faktablad presenteras resultat från år 1999 och framåt, eftersom effekten från de numera stängda reaktorerna varit obetydlig från det året. • Omgivningsfaktorerna temperatur, salthalt och siktdjup vid fiske har fluktuerat under åren 1999–2022 utan att några trender kan urskiljas. • Resultaten visar att det kustnära fisksamhället i Barsebäck har förändrats sedan 1999 där antalet mesopredatorer (icke-rovfisk) har ökat. • Stor fisk i fångsten har oftast varit ål eller torsk. Ål har bortsett från 2005 och 2010 varit talrikast i fångsten sett till individer över MRB (minsta referensstorlek för bevarande). • Det totala antalet fiskar i fångsten har ökat under perioden 1999–2019. Detta förklaras av att flera arter som skrubbskädda, abborre och tånglake visar en ökande trend. • Den vanligaste arten i fångsten, med avseende på antal, har varit strandkrabba som i snitt svarat för 75 procent av fångsten. Den vanligaste fiskarten till antalet har varit ål (gulål och blankål) tätt följt av tånglake, skrubbskädda och torsk som vardera stått för 3–4 procent av fångsten. • Fyra arter som har förekommit i fångsten återfinns på ArtDatabankens rödlista (version 2020): torsk, lyrtorsk, vitling och ål. • Under provfisket 2021 och 2022, som utfördes enligt den reviderade provfiskemetoden, har ansträngningen minskat och fler djupstrata tillkommit. Shannon-Wieners diversitetsindex låg 2021-2022 på liknande nivå som provfisket enligt den äldre fiskemetoden 1999-2019. • Den invasiva främmande arten svartmunnad smörbult fångades för första gången i Barsebäck 2021 och återfanns i fångsten 2022

Consequences of the COVID-19 Pandemic and Governmental Containment Policies on the Detection and Therapy of Oral Malignant Lesions-A Retrospective, Multicenter Cohort Study from Germany

(1) Background: In response to the global COVID-19 pandemic, governmental measures have been undertaken. The impact of the crisis on the healthcare of patients with cancer is largely unexplored. This multicenter cohort study aimed to investigate a potential screening delay and its consequences in patients with oral cancer (OC) during the pandemic. (2) Material and Methods: Data of patients who were first diagnosed with OC during different periods were collected, especially in terms of OC incidence, tumor stage/entity and time to intervention. The periods lockdown (LD) (13 March-16 June 2020), post-lockdown (PLD) (17 June-1 November 2020), and the corresponding equivalents in 2018/19 were differentiated and compared. (3) Results: There was no obvious trend towards a higher incidence of OC or higher tumor stages, whereas a trend towards a shorter time to intervention during the LD2020 could be observed. Subgroup analyses revealed an increased incidence in OC within the PLD2020 in Mainz, which might be explained by the partial closure of dental practices in this federal state during LD. (4) Conclusions: While there was no overall higher incidence of OC, we found closure of practices during LD to possibly delay cancer diagnosis. Therefore, measures must be taken to identify patients at risk and to ensure basic healthcare, especially in the context of dental screening measures

Biologisk recipientkontroll för Ringhals kärnkraftverk : årsrapport för 2022

Ringhals kärnkraftverk är en av Sveriges största elproducenter. På grund av intag och utsläpp av havsvatten som kyler processen i kraftverket sker en påverkan på den omgivande kustvattenmiljön. Denna påverkan övervakas och analyseras i det biologiska recipientkontrollprogrammet. Föreliggande årsrapport presenterar resultat av undersökningarna inom kontrollprogrammet för 2022. Fokus i årsrapporten ligger på samhället av fisk och skaldjur, förluster av ägg, larver och yngel i kylvattenvägarna samt förekomsten av främmande arter. I kylvattenintaget utförs under våren två olika årliga provtagningar för att övervaka förlusterna av olika fiskstadier i kraftverket: En provtagning av fiskägg och fisklarver med en Bongohåv, och en provtagning av yngel och juvenil fisk med en modifierad Isaac-Kidd-trål. I ägg- och larvprovtagningen 2022 var de vanligaste förekommande fiskäggen från torsk och de vanligaste fisklarverna från skrubbskädda och tobis (kust-/havs-). Provtagningen i kylvattenintaget efter juvenil fisk och yngel är till stor del fokuserad på fångsterna av glasål (Anguilla anguilla). Fångsterna med Isaac-Kidd-trålen 2022 dominerades av sillyngel följt av klarbult, tobisyngel och glasål. Effekten av utgående uppvärmt kylvatten undersöks genom årliga provfisken på tre lokaler: recipientområdet vid Ringhals, som påverkas av kylvattnet, referensområdet vid Vendelsö, som är opåverkat av kylvatten, och området vid Norra Horta, som är delvis påverkat av kylvattnet. Provfisket genomförs två gånger per år, under april och augusti. För 2022 var skärsnultra generellt den vanligaste fiskarten vid provfisket, förutom under april i referensområdet där stensnultra var vanligast. Generellt var förekomsten av varmvattengynnade arter högre i recipientområdet och förekomsten av kallvattengynnade arter högre i referensområdet. Totalfångsten av strandkrabba var hög i samtliga lokaler och fiskeperioder, med kulmen i recipientområdet i augusti. Området kring renshusledningens utlopp undersöktes med ROV (Remotely Operated Vehicle) för att visuellt inspektera påverkan på botten. Utsläpp och sedimentation av skaldelar från musslor och krabbor har även i år minskat till följd av relativt lågt kylvattenflöde. För att undersöka eventuell förekomst av invasiva främmande arter genomfördes en dykkartering i fem områden utanför kraftverkets kylvattenutsläpp. Sammantaget för de fem områdena observerades det sex invasiva främmande arter av alger (rödsvansing, japantofs, japanplym, agaralg, japansk sargassotång, och grönalgen klykalg) samt en främmande djurart (stillahavsostron). Utöver dykkarteringen så hittades även blåskrabba under provfisket i april. Samtliga främmande arter är kända på svenska västkusten sedan tidigare

Immunomodulation with romiplostim as a second-line strategy in primary immune thrombocytopenia: The iROM study.

Thrombopoietin receptor agonists (TPO-RAs) stimulate platelet production, which might restore immunological tolerance in primary immune thrombocytopenia (ITP). The iROM study investigated romiplostim's immunomodulatory effects. Thirteen patients (median age, 31 years) who previously received first-line treatment received romiplostim for 22 weeks, followed by monitoring until week 52. In addition to immunological data, secondary end-points included the sustained remission off-treatment (SROT) rate at 1 year, romiplostim dose, platelet count and bleedings. Scheduled discontinuation of romiplostim and SROT were achieved in six patients with newly diagnosed ITP, whereas the remaining seven patients relapsed. Romiplostim dose titration was lower and platelet count response was stronger in patients with SROT than in relapsed patients. In all patients, regulatory T lymphocyte (Treg) counts increased until study completion and the counts were higher in patients with SROT. Interleukin (IL)-4, IL-9 and IL-17F levels decreased significantly in all patients. FOXP3 (Treg), GATA3 (Th2) mRNA expression and transforming growth factor-β levels increased in patients with SROT. Treatment with romiplostim modulates the immune system and possibly influences ITP prognosis. A rapid increase in platelet counts is likely important for inducing immune tolerance. Better outcomes might be achieved at an early stage of autoimmunity, but clinical studies are needed for confirmation

Skin blood flow responses to acetylcholine and local heating at rest and 60%V O2max, and associated nitric oxide contribution, in boys vs. girl

To determine sex-related differences in the skin-blood-flow (SkBF) response to exercise, local heating, and acetylcholine (ACh) in children. Additionally, the contribution of nitric oxide (NO) was examined. Methods: Forearm SkBF during local heating (44˚C), ACh iontophoresis, and exercise (30 min cycling, 60% OV 2max) was assessed, using Laser-Doppler fluxmetry, in 12 boys and 12 girls (7–13 yrs old), with and without NO synthase inhibition, using Nω-nitro-L-arginine methyl ester (L-NAME) iontophoresis. Results: Local-heating-induced and ACh-induced SkBF increase were not different between boys and girls (Local heating: 1445±900% and 1432±582% of baseline, , p=.57; ACh: 673±434% and 558±405% of baseline, respectively, p=0.18). Exercise-induced increase in SkBF was greater in boys than girls (528±290 and 374±192% of baseline, respectively, p=0.03). L-NAME blunted the SkBF response to ACh and during exercise (p<0.001), with no difference between sexes. Summary: SkBF responses to ACh and local heat stimuli were similar in boys and girls, while the increase in SkBF during exercise was greater in boys. The apparent role of NO was not different between boys and girls. It is suggested that the greater SkBF response in the boys during exercise is related to greater relative heat production and dissipation needs during this exercise intensity. The response to body-size-related workload should be further examined

Bulk cell density and Wnt/TGFbeta signalling regulate mesendodermal patterning of human pluripotent stem cells

In vitro differentiation of human pluripotent stem cells (hPSCs) recapitulates early aspects of human embryogenesis, but the underlying processes are poorly understood and controlled. Here we show that modulating the bulk cell density (BCD: cell number per culture volume) deterministically alters anteroposterior patterning of primitive streak (PS)-like priming. The BCD in conjunction with the chemical WNT pathway activator CHIR99021 results in distinct paracrine microenvironments codifying hPSCs towards definitive endoderm, precardiac or presomitic mesoderm within the first 24 h of differentiation, respectively. Global gene expression and secretome analysis reveals that TGFß superfamily members, antagonist of Nodal signalling LEFTY1 and CER1, are paracrine determinants restricting PS progression. These data result in a tangible model disclosing how hPSC-released factors deflect CHIR99021-induced lineage commitment over time. By demonstrating a decisive, functional role of the BCD, we show its utility as a method to control lineage-specific differentiation. Furthermore, these findings have profound consequences for inter-experimental comparability, reproducibility, bioprocess optimization and scale-up.DFG/REBIRTHDFG/EXC62/1DFG/ZW 64/4-1DFG/MA 2331/16-1BMBF/13N12606BMBF/StemBANCCEU H2020/66872