Indigenous Arabs are descendants of the earliest split from ancient Eurasian populations

An open question in the history of human migration is the identity of the earliest Eurasian populations that have left contemporary descendants. The Arabian Peninsula was the initial site of the out-of-Africa migrations that occurred between 125,000 and 60,000 yr ago, leading to the hypothesis that the first Eurasian populations were established on the Peninsula and that contemporary indigenous Arabs are direct descendants of these ancient peoples. To assess this hypothesis, we sequenced the entire genomes of 104 unrelated natives of the Arabian Peninsula at high coverage, including 56 of indigenous Arab ancestry. The indigenous Arab genomes defined a cluster distinct from other ancestral groups, and these genomes showed clear hallmarks of an ancient out-of-Africa bottleneck. Similar to other Middle Eastern populations, the indigenous Arabs had higher levels of Neanderthal admixture compared to Africans but had lower levels than Europeans and Asians. These levels of Neanderthal admixture are consistent with an early divergence of Arab ancestors after the out-of-Africa bottleneck but before the major Neanderthal admixture events in Europe and other regions of Eurasia. When compared to worldwide populations sampled in the 1000 Genomes Project, although the indigenous Arabs had a signal of admixture with Europeans, they clustered in a basal, outgroup position to all 1000 Genomes non-Africans when considering pairwise similarity across the entire genome. These results place indigenous Arabs as the most distant relatives of all other contemporary non-Africans and identify these people as direct descendants of the first Eurasian populations established by the out-of-Africa migrations.All humans can trace their ancestry back to Africa (Cann et al. 1987), where the ancestors of anatomically modern humans first diverged from primates (Patterson et al. 2006), and then from archaic humans (Prüfer et al. 2014). Humans began leaving Africa through a number of coastal routes, where estimates suggest these “out-of-Africa” migrations reached the Arabian Peninsula as early as 125,000 yr ago (Armitage et al. 2011) and as late as 60,000 yr ago (Henn et al. 2012). After entering the Arabian Peninsula, human ancestors entered South Asia and spread to Australia (Rasmussen et al. 2011), Europe, and eventually, the Americas. The individuals in these migrations were the most direct ancestors of ancient non-African peoples, and they established the contemporary non-African populations recognized today (Cavalli-Sforza and Feldman 2003).The relationship between contemporary Arab populations and these ancient human migrations is an open question (Lazaridis et al. 2014; Shriner et al. 2014). Given that the Arabian Peninsula was an initial site of egress from Africa, one hypothesis is that the original out-of-Africa migrations established ancient populations on the peninsula that were direct ancestors of contemporary Arab populations (Lazaridis et al. 2014). These people would therefore be direct descendants of the earliest split in the lineages that established Eurasian and other contemporary non-African populations (Armitage et al. 2011; Rasmussen et al. 2011; Henn et al. 2012; Lazaridis et al. 2014; Shriner et al. 2014). If this hypothesis is correct, we would expect that there are contemporary, indigenous Arabs who are the most distant relatives of other Eurasians. To assess this hypothesis, we carried out deep-coverage genome sequencing of 104 unrelated natives of the Arabian Peninsula who are citizens of the nation of Qatar (Supplemental Fig. 1), including 56 of indigenous Bedouin ancestry who are the best representatives of autochthonous Arabs, and compared these genomes to contemporary genomes of Africa, Asia, Europe, and the Americas (The 1000 Genomes Project Consortium 2012; Lazaridis et al. 2014).     

A Novel Reference Security Model with the Situation Based Access Policy for Accessing EPHR Data

Electronic Patient Health Record (EPHR) systems may facilitate a patient not only to share his/her health records securely with healthcare professional but also to control his/her health privacy, in a convenient and easy way even in case of emergency. In order to fulfill these requirements, it is greatly desirable to have the access control mechanism which can efficiently handle every circumstance without negotiating security. However, the existing access control mechanisms used in healthcare to regulate and restrict the disclosure of patient data are often bypassed in case of emergencies. In this article, we propose a way to securely share EPHR data under any situation including break-the-glass (BtG) without compromising its security. In this regard, we design a reference security model, which consists of a multi-level data flow hierarchy, and an efficient access control framework based on the conventional Role-Based Access Control (RBAC) and Mandatory Access Control (MAC) policies.     

Pulmonary Impairment after Respiratory Viral Infections Is Associated with High Mortality in Allogeneic Hematopoietic Cell Transplant Recipients

Pulmonary impairment predicts increased mortality in many settings, and respiratory viral infection (RVI) causes considerable morbidity and mortality in allogeneic hematopoietic cell transplant recipients (allo-HCT). We hypothesized that pulmonary impairment after RVI, defined as a decline of forced expiratory volume in 1 second values by ≥10%, may identify allo-HCT recipients at high risk for mortality. We studied all allo-HCT recipients at our institution who had RVI with respiratory syncytial virus, parainfluenza virus, or influenza from 2004 to 2013 and had pre-RVI and post-RVI pulmonary function tests. We used competing risk regression models to identify risk factors for 2-year nonrelapse mortality (NRM) as the primary outcome after RVI and relapse-related mortality as a competing risk. From 223 eligible patients, pulmonary impairment after RVI was associated with over a 3-fold increase in 2-year NRM (pulmonary impairment, 25.3%; no impairment, 7.4%; univariate subhazard ratio [SHR], 3.9; 95% confidence interval [CI], 1.9 to 8.1; P < .001). After adjusting for age and systemic steroid use, pulmonary impairment after RVI was still associated with increased 2-year NRM (SHR, 3.3 [95% CI, 1.6 to 6.9]; P?=?.002). After adjustment for race and graft-versus-host disease (GVHD) prophylaxis, chronic GVHD at the time of RVI (odds ratio [OR], 2.8 [95% CI, 1.4 to 5.4]; p?=?.003) and lymphopenia (OR, 2.2 [95% CI, 1.1 to 4.2]; P?=?.02) were associated with increased odds of pulmonary impairment, whereas use of nonmyeloablative conditioning was associated with reduced odds of pulmonary impairment (OR, .4 [95% CI, .2 to .8]; P?=?.006). In allo-HCT recipients with RVIs, pulmonary impairment after RVI is associated with high NRM at 2years.     

Etiology of acute viral respiratory infections common in Pakistan: A review

Respiratory infections, especially those of the lower respiratory tract, remain a foremost cause of mortality and morbidity of children greater than 5 years in developing countries including Pakistan. Ignoring these acute‐level infections may lead to complications. Particularly in Pakistan, respiratory infections account for 20% to 30% of all deaths of children. Even though these infections are common, insufficiency of accessible data hinders development of a comprehensive summary of the problem. The purpose of this study was to determine the prevalence rate in various regions of Pakistan and also to recognize the existing viral strains responsible for viral respiratory infections through published data. Respiratory viruses are detected more frequently among rural dwellers in Pakistan. Lower tract infections are found to be more lethal. The associated pathogens comprise respiratory syncytial virus (RSV), human metapneumovirus (HMPV), coronavirus, enterovirus/rhinovirus, influenza virus, parainfluenza virus, adenovirus, and human bocavirus. RSV is more dominant and can be subtyped as RSV‐A and RSV‐B (BA‐9, BA‐10, and BA‐13). Influenza A (H1N1, H5N1, H3N2, and H1N1pdm09) and Influenza B are common among the Pakistani population. Generally, these strains are detected in a seasonal pattern with a high incidence during spring and winter time. The data presented include pneumonia, bronchiolitis, and influenza. This paper aims to emphasise the need for standard methods to record the incidence and etiology of associated pathogens in order to provide effective treatment against viral infections of the respiratory tract and to reduce death rates.     

Peripheral Blood versus Bone Marrow from Unrelated Donors: Bone Marrow Allografts Have Improved Long-Term Overall and Graft-versus-Host Disease-Free,Relapse-Free Survival

Peripheral blood (PB) and bone marrow (BM) from unrelated donors can serve as a graft source for hematopoietic cell transplantation (HCT). Currently, PB is most commonly used in roughly 80% of adult recipients. Determining the long-term impact of graft source on outcomes would inform this decision. Data collected by the Center for International Blood and Marrow Transplant Research from 5200 adult recipients of a first HCT from an 8/8 or 7/8 HLA antigen-matched unrelated donor for treatment of acute leukemia, chronic myelogenous leukemia, or myelodysplastic syndrome between 2001 and 2011 were analyzed to determine the impact of graft source on graft-versus-host disease (GVHD) relapse-free survival (GRFS), defined as freedom from grade III/IV acute GVHD, chronic GVHD requiring immunosuppressive therapy, relapse, and death, and overall survival. GRFS at 2 years was superior in BM recipients compared with PB recipients (16%; 95% confidence interval [CI], 14% to 18% versus 10%; 95% CI, 8% to 11%; P <.0001) in the 8/8 HLA-matched cohort and 7/8 HLA-matched cohort (11%; 95% CI, 8% to 14% versus 5%; 95% CI, 4% to 7%; P?=?.001). With 8/8 HLA-matched unrelated donors, overall survival at 5 years was superior in recipients of BM (43%; 95% CI, 40% to 46% versus 38%; 95% CI, 36% to 40%; P?=?.014). The inferior 5-year survival in the PB cohort was attributable to a higher frequency of deaths while in remission compared with the BM cohort. For recipients of 7/8 HLA-matched grafts, survival at 5 years was similar in BM recipients and PB recipients (32% versus 29%; P?=?.329). BM grafts are associated with improved long-term GRFS and overall survival in recipients of matched unrelated donor HCT and should be considered the unrelated allograft of choice, when available, for adults with acute leukemia, chronic myelogenous leukemia, and myelodysplastic syndrome.     

Employment,Insurance, and Financial Experiences of Patients with Chronic Graft-versus-Host Disease in North America

Understanding the socioeconomic impact of chronic graft-versus-host disease (GVHD) on affected patients is essential to help improve their overall well-being. Using data from the Chronic GVHD Consortium, we describe the insurance, employment, and financial challenges faced by these patients and the factors associated with the ability to work/attend school and associated financial burdens. A 15-item cross-sectional questionnaire designed to measure financial concerns, income, employment, and insurance was completed by 190 patients (response rate, 68%; 10 centers) enrolled on a multicenter Chronic GVHD Consortium Response Measures Validation Study. Multivariable logistic regression models examined the factors associated with financial burden and ability to work/attend school. The median age of respondents was 56years, and 87% of the patients were white. A higher proportion of nonrespondents had lower income before hematopoietic cell transplantation and less than a college degree. All but 1 patient had insurance, 34% had faced delayed/denied insurance coverage for chronic GVHD treatments, and 66% reported a financial burden. Patients with a financial burden had greater depression/anxiety and difficulty sleeping. Nonwhite race, lower mental functioning, and lower activity score were associated with a greater likelihood of financial burden. Younger age, early risk disease, and higher mental functioning were associated with a greater likelihood of being able to work/attend school. In this multicenter cohort of patients with chronic GVHD, significant negative effects on finances were observed even with health insurance coverage. Future research should investigate potential interventions to provide optimal and affordable care to at-risk patients and prevent long-term adverse financial outcomes in this vulnerable group.     

Comparison of 4% articaine with 1:100,000 epinephrine and 2% lidocaine with 1:100,000 epinephrine when used as a supplemental anesthetic

A randomized, double-blind trial was conducted to compare the efficacy of 4% articaine with 1:100,000 epinephrine and 2% lidocaine with 1:100,000 epinephrine when used as a supplemental anesthetic. Forty-eight patients with irreversible pulpitis requiring supplemental buccal infiltration for endodontic therapy were given either 4% articaine with 1:100,000 epinephrine or 2% lidocaine with 1:100,000 epinephrine in a double-blind manner. A standard VAS pain scale was used to evaluate the patient's response to pain after a supplemental injection. The mean VAS score after supplemental anesthesia was 15.28 for 4% articaine with 1:100,000 epinephrine and 19.70 for 2% lidocaine with 1:00,000 epinephrine. The mean percentage change in VAS score was 70.5 and 62.2% for articaine and lidocaine, respectively. There was no statistically significant difference in the VAS pain score between 4% articaine with 1:00,000 epinephrine and 2% lidocaine with 1:00,000 epinephrine as a supplemental anesthetic.