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In European Neolithic populations, the arrival of farmers prompted admixture with local hunter-gatherers over many centuries, resulting in distinct signatures in each region due to a complex series of interactions. Early European union of farmers David Reich and colleagues analyse genome-wide data from 180 individuals from the Neolithic and Chalcolithic periods of Hungary, Germany and Spain to study the population dynamics of Neolithization in European prehistory. They examine how gene flow reshaped European populations during the Neolithic period, including pervasive admixture—the interbreeding between previously isolated populations—between groups with different ancestry profiles. In each region, they find that the arrival of farmers prompted admixture with local hunter-gatherers, over the course of 3,000 years. Ancient DNA studies have established that Neolithic European populations were descended from Anatolian migrants 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 who received a limited amount of admixture from resident hunter-gatherers 3 , 4 , 5 , 9 . Many open questions remain, however, about the spatial and temporal dynamics of population interactions and admixture during the Neolithic period. Here we investigate the population dynamics of Neolithization across Europe using a high-resolution genome-wide ancient DNA dataset with a total of 180 samples, of which 130 are newly reported here, from the Neolithic and Chalcolithic periods of Hungary (6000–2900 bc , n  = 100), Germany (5500–3000 bc , n  = 42) and Spain (5500–2200 bc , n  = 38). We find that genetic diversity was shaped predominantly by local processes, with varied sources and proportions of hunter-gatherer ancestry among the three regions and through time. Admixture between groups with different ancestry profiles was pervasive and resulted in observable population transformation across almost all cultural transitions. Our results shed new light on the ways in which gene flow reshaped European populations throughout the Neolithic period and demonstrate the potential of time-series-based sampling and modelling approaches to elucidate multiple dimensions of historical population interactions.

Ancient DNA studies have established that Neolithic European populations were descended from Anatolian migrants1–8 who received a limited amount of admixture from resident hunter-gatherers3–5,9. Many open questions remain, however, about the spatial and temporal dynamics of population interactions and admixture during the Neolithic period. Using the highest-resolution genome-wide ancient DNA data set assembled to date—a total of 180 samples, 130 newly reported here, from the Neolithic and Chalcolithic of Hungary (6000–2900 BCE, n = 100), Germany (5500–3000 BCE, n = 42), and Spain (5500–2200 BCE, n = 38)—we investigate the population dynamics of Neolithization across Europe. We find that genetic diversity was shaped predominantly by local processes, with varied sources and proportions of hunter-gatherer ancestry among the three regions and through time. Admixture between groups with different ancestry profiles was pervasive and resulted in observable population transformation across almost all cultural transitions. Our results shed new light on the ways that gene flow reshaped European populations throughout the Neolithic period and demonstrate the potential of time-series-based sampling and modeling approaches to elucidate multiple dimensions of historical population interactions.

Ancient DNA studies have established that European Neolithic populations were descended from Anatolian migrants who received a limited amount of admixture from resident hunter-gatherers. Many open questions remain, however, about the spatial and temporal dynamics of population interactions and admixture during the Neolithic period. Using the highest-resolution genome-wide ancient DNA data set assembled to date --- a total of 177 samples, 127 newly reported here, from the Neolithic and Chalcolithic of Hungary (6000-2900 BCE, n = 98), Germany (5500-3000 BCE, n = 42), and Spain (5500-2200 BCE, n = 37) --- we investigate the population dynamics of Neolithization across Europe. We find that genetic diversity was shaped predominantly by local processes, with varied sources and proportions of hunter-gatherer ancestry among the three regions and through time. Admixture between groups with different ancestry profiles was pervasive and resulted in observable population transformation across almost all cultural transitions. Our results shed new light on the ways that gene flow reshaped European populations throughout the Neolithic period and demonstrate the potential of time-series-based sampling and modeling approaches to elucidate multiple dimensions of historical population interactions.

ObjectivesHeart rate (HR) is one of the physiological variables in the early assessment of trauma-related haemorrhagic shock, according to Advanced Trauma Life Support (ATLS). However, its efficiency as predictor of mortality is contradicted by several studies. Furthermore, the linear association between HR and the severity of shock and blood loss presented by ATLS is doubtful. This systematic review aims to update current knowledge on the role of HR in the initial haemodynamic assessment of patients who had a trauma.DesignThis study is a systematic review and meta-regression that follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations.Data sourcesEMBASE, MEDLINE, CENTRAL and Web of Science databases were systematically searched through on 1 September 2020.Eligibility criteriaPapers providing early HR and mortality data on bleeding patients who had a trauma were included. Patient cohorts were considered haemorrhagic if the inclusion criteria of the studies contained transfusion and/or positive focused assessment with sonography for trauma and/or postinjury haemodynamical instability and/or abdominal gunshot injury. Studies on burns, traumatic spinal or brain injuries were excluded. Papers published before January 2010 were not considered.Data extraction and synthesisData extraction and risk of bias were assessed by two independent investigators. The association between HR and mortality of patients who had a trauma was assessed using meta-regression analysis. As subgroup analysis, meta-regression was performed on patients who received blood products.ResultsFrom a total of 2017 papers, 19 studies met our eligibility criteria. Our primary meta-regression did not find a significant relation (p=0.847) between HR and mortality in patients who had a trauma with haemorrhage. Our subgroup analysis included 10 studies, and it could not reveal a linear association between HR and mortality rate.ConclusionsIn accordance with the literature demonstrating the multiphasic response of HR to bleeding, our study presents the lack of linear association between postinjury HR and mortality. Modifying the pattern of HR derangements in the ATLS shock classification may result in a more precise teaching tool for young clinicians.

The hunt for useful sepsis biomarkers is ongoing. Macrophage migration inhibitory factor (MIF) was implicated as a biomarker in sepsis, but its diagnostic and prognostic value has remained unclear in human studies. Here, we aimed at clarifying the value of MIF as a sepsis biomarker with the meta-analysis of clinical trials. PubMed, EMBASE, and Cochrane Central Register of Controlled Trials databases were searched until December 2019. From the included studies, blood MIF levels and indicators of disease severity were extracted in septic and control patient groups. Twenty-one eligible studies were identified, including data from 1876 subjects (of which 1206 had sepsis). In the septic patients, blood MIF levels were significantly higher than in healthy controls with a standardized mean difference (SMD) of 1.47 (95% confidence interval, CI: 0.96–1.97; p  < 0.001) and also higher than in patient groups with nonseptic systemic inflammation (SMD = 0.94; CI: 0.51–1.38; p  < 0.001). Markedly greater elevation in blood MIF level was found in the more severe forms of sepsis and in nonsurvivors than in less severe forms and in survivors with SMDs of 0.84 (CI: 0.45–1.24) and 0.75 (CI: 0.40–1.11), respectively ( p  < 0.001 for both). In conclusion, blood MIF level is more elevated in systemic inflammation caused by infection (i.e., sepsis) compared to noninfectious causes. In more severe forms of sepsis, including fatal outcome, MIF levels are higher than in less severe forms. These results suggest that MIF can be a valuable diagnostic and prognostic biomarker in sepsis given that well-designed clinical trials validate our findings.

Vaccine-induced immunity is essential for controlling the COVID-19 pandemic. Data on humoral and cellular immunogenicity and safety of different SARS-CoV-2 vaccines in patients with autoimmune rheumatic and musculoskeletal diseases (RMDs) are limited. A single center observational study evaluated the immunogenicity and safety of the two-dose regimen of the BBIBP-CorV inactivated, Gam-COVID-Vac and AZD1222 adenovirus-based, and BNT162b2 and mRNA-1273 mRNA-based vaccines in patients with RMDs (n = 89) compared with healthy controls (n = 74). Neutralizing anti-RBD (receptor binding domain) specific antibodies and SARS-CoV-2 specific T-cell response were measured one and four months after the second vaccine dose in parallel with vaccination efficacy and safety. Disease-specific comparison showed that antibody response at four months was higher in spondylarthropathies compared to rheumatoid arthritis and autoimmune RMDs. Risk factors for reduced immunogenicity included longer disease duration, positive immunoserological profile and anti-CD20 therapy of patients. The rate of positive anti-RBD antibody response for healthy controls versus patients after 4 months post vaccination was 69% vs. 55% for the inactivated viral vaccine BBIBP-CorV, 97% vs. 53% for the pooled data of adenovirus vector-based vaccines Gam-COVID-Vac and AZD1222, or 100% vs. 81% for the pooled data of mRNA vaccines BNT162b2 and mRNA-1273, respectively. Patients who received the Gam-COVID-Vac or mRNA-1273 vaccines had a higher proportion of TNF-α producing CD4+ T-cells upon SARS-CoV-2 antigen stimulation compared to the inactivated viral vaccine. All five investigated vaccines were immunogenic in the majority of patients and healthy controls with variable antibody and T-cell response and an acceptable safety profile.

Purpose There is still no generally accepted quality model of consulting services. This is particularly the case for management consulting projects, where scope is often indefinite. The purpose of this paper is to identify the clients’ underlying utility preferences and their perceived quality dimensions. Design/methodology/approach The research is a qualitative data collection from 22 expert interviews performed in the financial service sector. Interviewees from the client-side were decision-makers from different hierarchical levels with considerable experience in working with consultants, while the consultant sample was obtained by selecting professionals with relevant project experience. The model development was based on the grounded theory. Findings Based on a content analysis of a 600-page transcript of interviews, it was found that customers construct their judgments on consulting service quality through five main attributes: consultants, client adaption, consulting process, deliverables and communication. Because of the strong overlaps of the attributes, four better separable quality dimensions – as a conceptual model – were identified: expertise, relations, involvement and performance. Practical implications Among managerial implications for consulting firms, support of buying organization in setting clear project objectives, flexibility in partnership and readiness for overperformance can be underlined. Originality/value There is little empirical research that focuses on the conceptualization of management consulting service quality from a client perspective. The value of the paper is the exploration of perceived service quality dimensions of management consulting projects and a consulting context-specific list of quality attributes.

A vezetési tanácsadás egy feltételezett kompetenciával bíró szakértő csoport által tett megoldási javaslat. Az üzleti probléma jellege alapján nem mindig definiálható egyértelműen, hogy a tranzakcióban milyen fokú együttműködés várható el a felek között. A tanácsadási szolgáltatás jelentős mértékben befolyásolhatja a vevő üzleti sikerét, ezért magas kapcsolati komplexitású szolgáltatásról van szó, ahol kiemelt szerepe van a kölcsönösségnek és a bizalomnak. Az ügyfél-tanácsadó kapcsolat és a tanácsadók által kialakított szerepkörök és tanácsadói stílus nagyban befolyásolják az ügyfelek értékítéletét a szolgáltatás minőségéről, ezért kiemelkedően fontos mindkét fél számára, hogy megértsék a tanácsadók szerepét és feladatait. A tanulmány bemutatja a legfontosabb szerepklasszifikációs modelleket, feltárva a kutatási terület főbb irányait. Huszonkét feltáró szakértői mélyinterjús kutatás eredményére támaszkodva kísérletet tesz a különböző tanácsadói szerepek bemutatására, valamint rávilágít a szervezeti hierarchia különböző szintjein lévők preferencia-attribútumaira.

Herpes simplex viruses (HSV) produce age-dependent encephalitis characterized by more severe involvement of the cerebral cortex in younger hosts. To elucidate the potential role of the major neural entry receptor of HSV, nectin-1, in age-dependent susceptibility of cortical neurons to viral encephalitis, the authors examined the anatomical distribution of the receptor protein in the developing human and mouse cerebral cortex, hippocampus, and cerebellum by immunohistochemistry. Nectin-1 is expressed at high levels in guiding cells (radial glial cells and Cajal-Retzius cells) that regulate radial migration of neurons in cortical lamination, at lower levels in migrating neurons, and at variable levels in the transient ventricular and marginal zones of the cerebral cortical wall. These results may have implications regarding the selective spatiotemporal tropism of HSV to specific neuronal populations, and for the better understanding of neurodevelopmental defects caused by fetal HSV infections.