Characterization of greater middle eastern genetic variation for enhanced disease gene discovery

The Greater Middle East (GME) has been a central hub of human migration and population admixture. The tradition of consanguinity, variably practiced in the Persian Gulf region, North Africa, and Central Asia1-3, has resulted in an elevated burden of recessive disease4. Here we generated a whole-exome GME variome from 1,111 unrelated subjects. We detected substantial diversity and admixture in continental and subregional populations, corresponding to several ancient founder populations with little evidence of bottlenecks. Measured consanguinity rates were an order of magnitude above those in other sampled populations, and the GME population exhibited an increased burden of runs of homozygosity (ROHs) but showed no evidence for reduced burden of deleterious variation due to classically theorized ‘genetic purging’. Applying this database to unsolved recessive conditions in the GME population reduced the number of potential disease-causing variants by four- to sevenfold. These results show variegated genetic architecture in GME populations and support future human genetic discoveries in Mendelian and population genetics

Begagna artificiell intelligens för bestående organisationella konkurrensfördelar : En studie i naturlig språkbehandling och dynamiska förmågor

Technologies such as Artificial Intelligence (AI) and Machine Learning (ML)are disrupting industries worldwide and are being categorized as drivers of a technological revolution. The economic impact is hypothesized to amount to hundreds of billions of US dollars in losses of wages, affecting governmental tax revenue streams consequentially. Firms that manage to leverage these technologies by developing sustained competitive advantage are ultimately the firms that will prosper. Competitive advantage stems from the dynamic capabilities, characterizing the organizational and managerial processes in place to withstand the effects of external environmental turbulence, as with the technological revolution galvanized by AI. This research aimed to analyze how a tele- & cloud-communication company manages to leverage AI to materialize competitive advantage. The research was conducted in two principal parts. First, by developing an ML model for language agnostic document retrieval (LaDPR) and evaluating the performance vs. Facebook’s Dense Passage Retrieval (DPR) model. The ML experiments show that the developed LaDPR model outperforms Facebook’s DPR model by over 2x on average, on multilingual document retrieval. This performance increase rises to over 4x when excluding English, which is the language that DPR was trained on. Secondly, interviews were conducted with key representatives to research how such technological advancements can be exploited in the organizational goal for competitive advantage. Specific vital capabilities such as automated decision-making, knowledge integration, and platform maturity are the three prominent organizational and managerial processes that advanced AI systems can undergird. The results pinpoint that the process of a high-technology department focused solely on developing such AI systems, packaging them with engineering competence to then transfer ownership internally in the organization, ultimately coalesce into hard-to-imitate dynamic capabilities, materializing competitive advantage.Teknologier som Artificiell Intelligens (AI) och Maskininlärning (ML) splittrar industrier världen över, och kategoriseras som drivkrafter bakom en teknologisk revolution. Effekterna på ekonomin spekuleras uppnå hundratals miljarder USD, som påverkar staters skatteintäkter markant. Företag som lyckas begagna sådan teknologi genom att utveckla långvariga konkurrensfördelar är i slutändan de företag som kommer se framgång. Dessa fördelar härstammar från de dynamiska förmågorna i ett företag, och karakteriseras av organisationella och lednings-orienterade processer som används för att stå emot effekterna av utomstående fluktuationer i marknaden, exemplifierat av den teknologiska revolutionen driven av AI. Den bedrivna forskningen ämnade att analysera hur ett företag inom tele- och molnkommunikation begagnar AI för att materialisera konkurrensfördelar. Forskningen bedrevs i två primära delar. Först, genom att utveckla en ML modell för språkagnostisk dokumenthämtning (LaDPR), och utvärdera prestandan i jämförelse med Facebooks Dense Passage Retrieval (DPR) modell. ML experimenten visar att den utvecklade LaDPR modellen presterar i snitt 2x bättre än Facebooks DPR modell på flerspråkig dokument-hämtning. Prestandaförbättringarna stiger upp till 4x, ifall engelska exkluderas, vilket är det språk som DPR tränades på. Genom att föra intervjuer med nyckelpersoner undersöktes det hur sådana teknologiska framsteg exploateras i de organisationella målen för konkurrensfördelar. Specifika nyckelförmågor som automatiserat beslutsfattande, kunskapsintegrering och plattformmognad är tre huvudsakliga organisationella och ledningsorienterade processer som avancerade AI system kan underbinda. Resultaten visar att processen av en högteknologisk avdelning som fokuserar på utveckling av avancerade AI system, som sedan paketeras tillsammans med ingenjörskompetens, för slutgiltig överföring av ägarskap, i slutändan förenas i svårimiterade dynamiska förmågor, som materialiseras i konkurrensfördelar.

The position of Iraqi women within the family: with particular reference to married women

The central theme of this research is an investigation of the extent to which traditional familial attitudes have been instilled in Iraqi women, resulting in deep conflicts amongst those who recognise modern liberalising trends. By allowing Iraqi women to voice their opinions, this study exposes the deep dicotomy within their society. The Western view that Islam is responsible for perpetuating archaic attitudes towards women is also questioned in some depth, together with the idea of the ideology of honour and shame as a means of social control. It will be shown that, because of their socialization (which implicitly incorporates these ideologies and instils feelings of inferiority into the young female) many women carry these ideals into adulthood and marriage. Marital relations, therefore, are examined in some detail. This research shows that many women, particularly working women, suffer a considerable degree of stress. Such problems are perceived at an individual rather than a societal level which inhibits development of any collective consciousness and hinders any improvement of their position within the family. Modern Iraq is still a traditional society in many ways, but enlightened modernisation programmes are bringing about widespread change. Education and work schemes promoted by the Arab Ba'th Socialist Party, are helping to improve the position of women - it is hoped that this research will contribute to this cause

Effects of a Physical Activity Program that Incorporates Exercises Targeting Balance, Strength, and Proprioception on Cognitive Functions and Physical Performance in Old Adults with Mild Cognitive Impairment.

International audienceBackground:Aging often leads to cognitive function decline, sensory structure deterioration, and musculoskeletal system weakening. This impacts postural control during static and dynamic activities like walking, increasing the fall risk among the elderly. Older adults with mild cognitive impairment (MCI) face an elevated fall risk and cognitive decline, magnifying the public health concern. Objective:This study aimed to explore solutions by investigating the effects of a multi-component physical activity program on cognitive and motor functions in MCI patients. Methods:Twenty-three participants were enrolled in the study and assigned into two groups: an intervention group (n = 13; age = 85.7±5.5 years) and a control group (n = 9; age = 85±6.7 years). The study spanned two months, with participants engaging in three 60-minute weekly physical exercise sessions. The intervention focused on improving proprioception, muscle strength, and balance. Results:Results demonstrated significant enhancements in physical performance, fall risk reduction, and balance (p  0.05). Predictive models for outcomes were developed using linear regression analysis during the follow-up stage. Conclusions:This study underscores the effectiveness of a multi-component physical activity program encompassing balance, proprioception, and muscle-strengthening exercises as a non-pharmaceutical approach in improving balance skills and playing a key role in mitigating the risk of falls among old adults with MCI

Gastrointestinal Hormones, Morphological Characteristics, and Physical Performance in Elite Soccer Players

International audiencePurpose: To determine the relationship between gastrointestinal hormones (leptin, glucagon-like peptide-1), ghrelin, cholecystokinin, peptide YY, morphological characteristics, and physical performances in elite soccer players. Methods: Q2 Twenty-two elite male soccer players (age = 23.1 [2.7] y, height = 177.0 [0.1] cm, weight = 70.2 [2.9] kg, body mass index = 22.1 [1.8] kg/m(2)) completed 3-day food records each week during the 5-week training period. Blood samples were drawn after an overnight fast before and after preseason training to assess gastrointestinal hormones (leptin, glucagon-like peptide-1, ghrelin, cholecystokinin, and peptide YY). Continuous analysis of the training load was used during the training period. Preintervention and postintervention tests assessed jumping (countermovement jump), sprinting (10, 20, and 30 m), and endurance fitness (the Yo-Yo Intermittent Recovery Test Level 1 [YYIRT1]) levels. Results: Preseason training decreased body mass index (P = .001; effect size [ES] = 0.183) and body fat percentage (P = .001; ES = 0.516). There were increases in countermovement jump (P = .032; ES = 0.215), 20-(P = .016; ES = 0.195) and 30-m sprints (P = .001; ES = 0.188), and YYIRT1 performance (P = .001; ES = 0.9). Levels of cholecystokinin, peptide YY, and ghrelin did not change during preseason training, although changes in leptin (P = .001; ES = 0.41) and glucagon-like peptide-1 levels (P = .039; ES = 0.606) were recorded. Leptinemia correlated with anthropometric parameters (body mass index, r= .77, P = .001; percentage of body fat, r = .67, P = .006) and the total distance covered during the YYIRT1 (r= -.54; P = .03). Conclusion: Changes in morphological parameters and physical performance in elite-level male soccer players are related to variations in selected gastrointestinal hormones

Age-dependent association between pulmonary tuberculosis and common TOX variants in the 8q12-13 linkage region.

International audienceOnly a small fraction of individuals infected with Mycobacterium tuberculosis develop clinical tuberculosis (TB) in their lifetime. Genetic epidemiological evidence suggests a genetic determinism of pulmonary TB (PTB), but the molecular basis of genetic predisposition to PTB remains largely unknown. We used a positional-cloning approach to carry out ultrafine linkage-disequilibrium mapping of a previously identified susceptibility locus in chromosomal region 8q12-13 by genotyping 3,216 SNPs in a family-based Moroccan sample including 286 offspring with PTB. We observed 44 PTB-associated SNPs (p < 0.01), which were genotyped in an independent set of 317 cases and 650 controls from Morocco. A single signal, consisting of two correlated SNPs close to TOX, rs1568952 and rs2726600 (combined p = 1.1 × 10(-5) and 9.2 × 10(-5), respectively), was replicated. Stronger evidence of association was found in individuals who developed PTB before the age of 25 years (combined p for rs1568952 = 4.4 × 10(-8); odds ratio of PTB for AA versus AG/GG = 3.09 [1.99-4.78]). The association with rs2726600 (p = 0.04) was subsequently replicated in PTB-affected subjects under 25 years in a study of 243 nuclear families from Madagascar. Stronger evidence of replication in Madagascar was obtained for additional SNPs in strong linkage disequilibrium with the two initial SNPs (p = 0.003 for rs2726597), further confirming the signal. We thus identified around rs1568952 and rs2726600 a cluster of SNPs strongly associated with early-onset PTB in Morocco and Madagascar. SNP rs2726600 is located in a transcription-factor binding site in the 3' region of TOX, and further functional explorations will focus on CD4 T lymphocytes