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92+5G>C) and FSC 5 (-CT) (HBB c.17_18delCT). The findings of the present study show differences with previous results from other regions of the Pashtun population, which demarcates the heterogeneity in mutations found in the Pashtun ethnicity. These observations may help in implementing parental meetings about disease recurrence in future, large scale mutation screening and PND for the population of the Kohat region and also the whole Pashtun ethnicity.Hemophilia arthropathy (HA) represents the majority of morbidity in severe hemophilia patients, especially in resource-limited countries. Adeno-associated virus (AAV)-mediated gene therapy is showing promise for managing hemophilia. this website However, patients with neutralizing antibodies (NAbs) against AAV, and inhibitors to clotting factors, are excluded from such therapy. This study explored the feasibility of AAV-mediated local gene therapy for HA. Factor VIII knockout (FVIII-/-) mice, with or without a FVIII inhibitor, were subjected to hemarthrosis induction and treated with either intravenous (IV) or intraarticular (IA) recombinant human factor VIII (rhFVIII). To investigate whether rhFVIII carried the risk to develop a FVIII inhibitor, FVIII-/- mice were treated with three doses of IV or IA rhFVIII and inhibitor development was measured. In patients with established HA requiring synovial fluid aspiration, plasma, and synovial fluid were collected and measured for anti-AAV capsid IgG (serotypes 1-9 and 843) and NAbs for AAV843. IA rhFVIII provided better protection from synovitis compared with IV rhFVIII, with or without the FVIII inhibitor. While IV rhFVIII led to all FVIII-/- mice developing an FVIII inhibitor (n = 31, median 4.9 Bethesda units [BU]/mL), only 50% of the mice developed a FVIII inhibitor by IA administration, and at a lower titer (median 0.55 BU/mL). In hemophilia patients, total anti-AAV IgG was lowest for AAV4 and AAV5, both in plasma and synovial fluid. Anti-AAV IgGs in synovial fluid for most samples were lower or similar to the plasma levels. These results show that direct IA rhFVIII administration yields better protection against bleeding-induced joint damage, even in the presence of an inhibitor antibody. IA rhFVIII delivery carried a lower risk of FVIII inhibitor formation compared with IV FVIII. The anti-AAV antibody level in synovial fluid was similar or lower than the plasma level, supporting the feasibility of local gene therapy for managing HA.Taking a Feminist perspective as a starting point, this introductory piece seeks not only to integrate women as the main agents within the history of humanitarian relief, but also to understand their assistance to victims, from the Franco-Prussian War to WWII, as a type of situated knowledge which was broadly associated with the notion of care through the implementation of practices such as dressing wounds, vaccinating, feeding and clothing vulnerable populations. This political and epistemological position allows us to analyse the agency of women humanitarians as a caring power involving strong gender, class, religious and colonial power relations within the history of Western Empires. Furthermore, our Feminist approach enables us to deconstruct the essentialist vision through which women humanitarians have frequently been depicted as compassionate mothers or loving angels, as well as to contextualize their contrasting experiences of complicity with Western Empires and resistance to male delegates and political and medical representatives. Far from heroic representations, women humanitarians had to navigate through complex global hierarchies although this did not necessarily come into conflict with their dreams about female emancipation.It is a common notion that phases-of-entrainment of circadian rhythms are adaptive, in that they enable organisms to time their behavior to specific times of the day to enhance their fitness. Therefore, understanding mechanisms that bring about such phases-of-entrainment is crucial to chronobiologists. Our previous studies have shown that selection for morning and evening phasing of adult emergence in Drosophila melanogaster populations leads to divergent coevolution of free-running periods of both adult emergence and activity/rest rhythms, such that early (morning) and late (evening) adult emergence chronotypes have shorter and longer circadian periods, respectively. However, there is little evidence to support the notion that phases-of-entrainment in these fly stocks is indeed driven by non-parametric mechanisms. Extending from a previous hypothesis based on anecdotal evidence for parametric mechanisms being in play, we explore the extent of non-parametric and parametric effects of light on circadian clocks of early and late chronotypes. We systematically tested predictions of the non-parametric model of entrainment, sketched the Circadian Integrated Response Characteristic (CIRC) of our stocks, assessed the effect of light pulses on amplitude of the behavior and the effect of duration of light pulse on phase-shifts of the clock. We demonstrate that, in addition to the differences in clock period, divergent CIRCs contribute to entrainment of the activity/rest rhythm. The differences in CIRC could be explained by differential transient amplitude responses and duration responses of the clock's phase between the early and late chronotypes. Our study thus highlights the role of amplitude responses and phase-shifts due to long durations of light in entrainment of circadian rhythms of D. melanogaster.The objective of the experiment was to analyse serum profiles of goslings with visceral gout and compare them with those of healthy individuals to identify differentially-abundant metabolites as potential biomarkers.Untargeted gas chromatography and time-of-flight mass spectrometry (GC-TOF-MS) metabolomic profiling was used to compare the serum metabolome of 15 goslings (Anser cygnoides) with gout and 15 healthy goslings (control).Goslings with gout had a metabolic profile distinct from that of the controls, with 45 metabolite levels differing significantly (VIP > 1; P less then 0.05) between both groups. Nine metabolites (hydrocortisone, glucose, trans-4-hydroxy-L-proline, galactose, 2-deoxy-D-galactose, beta-mannosylglycerate, d-glucoheptose, zymosterol, and hypoxanthine) were selected through receiver operating characteristics (ROC) analysis (area under curve (AUC) score ≥0.85) as potential biomarkers. Pathway analysis revealed that metabolites with differing levels were mainly involved in galactose, arginine and proline and purine metabolisms.