Population history from the Neolithic to present on the Mediterranean island of Sardinia: an ancient DNA perspective

Recent ancient DNA studies of western Eurasia have revealed a dynamic history of admixture, with evidence for major migrations during the Neolithic and Bronze Age. The population of the Mediterranean island of Sardinia has been notable in these studies –} Neolithic individuals from mainland Europe cluster more closely with Sardinian individuals than with all other present-day Europeans. The current model to explain this result is that Sardinia received an initial influx of Neolithic ancestry and then remained relatively isolated from expansions in the later Neolithic and Bronze Age that took place in continental Europe. To test this model, we generated genome-wide capture data (approximately 1.2 million variants) for 43 ancient Sardinian individuals spanning the Neolithic through the Bronze Age, including individuals from Sardinia{’}s Nuragic culture, which is known for the construction of numerous large stone towers throughout the island. We analyze these new samples in the context of previously generated genome-wide ancient DNA data from 972 ancient individuals across western Eurasia and whole-genome sequence data from approximately 1,500 modern individuals from Sardinia. The ancient Sardinian individuals show a strong affinity to western Mediterranean Neolithic populations and we infer a high degree of genetic continuity on the island from the Neolithic (around fifth millennium BCE) through the Nuragic period (second millennium BCE). In particular, during the Bronze Age in Sardinia, we do not find significant levels of the {“}Steppe{” ancestry that was spreading in many other parts of Europe at that time. We also characterize subsequent genetic influx between the Nuragic period and the present. We detect novel, modest signals of admixture between 1,000 BCE and present-day, from ancestry sources in the eastern and northern Mediterranean. Within Sardinia, we confirm that populations from the more geographically isolated mountainous provinces have experienced elevated levels of genetic drift and that northern and southwestern regions of the island received more gene flow from outside Sardinia. Overall, our genetic analysis sheds new light on the origin of Neolithic settlement on Sardinia, reinforces models of genetic continuity on the island, and provides enhanced power to detect post-Bronze-Age gene flow. Together, these findings offer a refined demographic model for future medical genetic studies in Sardinia

Overall Survival Benefit with Tebentafusp in Metastatic Uveal Melanoma

Background: Uveal melanoma is a disease that is distinct from cutaneous melanoma, with a low tumor mutational burden and a 1-year overall survival of approximately 50% in patients with metastatic uveal melanoma. Data showing a proven overall survival benefit with a systemic treatment are lacking. Tebentafusp is a bispecific protein consisting of an affinity-enhanced T-cell receptor fused to an anti-CD3 effector that can redirect T cells to target glycoprotein 100-positive cells. Methods: In this open-label, phase 3 trial, we randomly assigned previously untreated HLA-A*02:01-positive patients with metastatic uveal melanoma in a 2:1 ratio to receive tebentafusp (tebentafusp group) or the investigator's choice of therapy with single-agent pembrolizumab, ipilimumab, or dacarbazine (control group), stratified according to the lactate dehydrogenase level. The primary end point was overall survival. Results: A total of 378 patients were randomly assigned to either the tebentafusp group (252 patients) or the control group (126 patients). Overall survival at 1 year was 73% in the tebentafusp group and 59% in the control group (hazard ratio for death, 0.51; 95% confidence interval [CI], 0.37 to 0.71; P<0.001) in the intention-to-treat population. Progression-free survival was also significantly higher in the tebentafusp group than in the control group (31% vs. 19% at 6 months; hazard ratio for disease progression or death, 0.73; 95% CI, 0.58 to 0.94; P = 0.01). The most common treatment-related adverse events in the tebentafusp group were cytokine-mediated events (due to T-cell activation) and skin-related events (due to glycoprotein 100-positive melanocytes), including rash (83%), pyrexia (76%), and pruritus (69%). These adverse events decreased in incidence and severity after the first three or four doses and infrequently led to discontinuation of the trial treatment (2%). No treatment-related deaths were reported. Conclusions: Treatment with tebentafusp resulted in longer overall survival than the control therapy among previously untreated patients with metastatic uveal melanoma. (Funded by Immunocore; ClinicalTrials.gov number, NCT03070392; EudraCT number, 2015-003153-18.)

Creativity in Citizen Cyberscience

An interview study was conducted to explore volunteers’ experiences of creativity in citizen cyberscience. Participants were recruited from 4 projects: GeoTag-X, Virtual Atom Smasher, Synthetic Biology, and Extreme Citizen Science. Ninety-six interviews were conducted in total: 86 with volunteers (citizen scientists) and 10 with professional scientists. The resulting thematic analysis revealed that volunteers are involved in a range of creative activities, such as discussing ideas, suggesting improvements, gamification, artwork, creative writing, and outreach activities. We conclude that the majority of creative products are community-related. Creativity in citizen cyberscience is a collective process: volunteers create within a project and a community, both for themselves and for others

Treatment of bronchial airway obstruction using a rotating tip microdebrider: a case report

BACKGROUND: Central airway obstruction is a common complication of lung cancer. The microdebrider is a new device available for treatment of central airway obstruction. CASE DESCRIPTION: We report a case a 59-yr-old male with T3N2M1 non-small cell lung cancer with malignant distal left mainstem obstruction treated successfully with a novel elongated rotating tip microdebrider via rigid bronchoscopy with sufficient length to reach distal bronchial lesions. DISCUSSION AND CONCLUSION: The microdebrider is an excellent addition to the spectrum of interventions available for the management of central airway obstruction with advantages including accuracy and immediate removal of debris without a need for separate suctioning or limitation in oxygenation

The Human Connectome Project: A retrospective

The Human Connectome Project (HCP) was launched in 2010 as an ambitious effort to accelerate advances in human neuroimaging, particularly for measures of brain connectivity; apply these advances to study a large number of healthy young adults; and freely share the data and tools with the scientific community. NIH awarded grants to two consortia; this retrospective focuses on the WU-Minn-Ox HCP consortium centered at Washington University, the University of Minnesota, and University of Oxford. In just over 6 years, the WU-Minn-Ox consortium succeeded in its core objectives by: 1) improving MR scanner hardware, pulse sequence design, and image reconstruction methods, 2) acquiring and analyzing multimodal MRI and MEG data of unprecedented quality together with behavioral measures from more than 1100 HCP participants, and 3) freely sharing the data (via the ConnectomeDB database) and associated analysis and visualization tools. To date, more than 27 Petabytes of data have been shared, and 1538 papers acknowledging HCP data use have been published. The HCP-style neuroimaging paradigm has emerged as a set of best-practice strategies for optimizing data acquisition and analysis. This article reviews the history of the HCP, including comments on key events and decisions associated with major project components. We discuss several scientific advances using HCP data, including improved cortical parcellations, analyses of connectivity based on functional and diffusion MRI, and analyses of brain-behavior relationships. We also touch upon our efforts to develop and share a variety of associated data processing and analysis tools along with detailed documentation, tutorials, and an educational course to train the next generation of neuroimagers. We conclude with a look forward at opportunities and challenges facing the human neuroimaging field from the perspective of the HCP consortium

A telephone survey of cancer awareness among frontline staff: informing training needs

Background: Studies have shown limited awareness about cancer risk factors among hospital-based staff. Less is known about general cancer awareness among community frontline National Health Service and social care staff. Methods: A cross-sectional computer-assisted telephone survey of 4664 frontline community-based health and social care staff in North West England. Results: A total of 671 out of 4664 (14.4%) potentially eligible subjects agreed to take part. Over 92% of staff recognised most warning signs, except an unexplained pain (88.8%, n=596), cough or hoarseness (86.9%, n=583) and a sore that does not heal (77.3%, n=519). The bowel cancer-screening programme was recognised by 61.8% (n=415) of staff. Most staff agreed that smoking and passive smoking ‘increased the chance of getting cancer.’ Fewer agreed about getting sunburnt more than once as a child (78.0%, n=523), being overweight (73.5%, n=493), drinking more than one unit of alcohol per day (50.2%, n=337) or doing less than 30 min of moderate physical exercise five times a week (41.1%, n=276). Conclusion: Cancer awareness is generally good among frontline staff, but important gaps exist, which might be improved by targeted education and training and through developing clearer messages about cancer risk factors

Integrating the promotion of physical activity within a smoking cessation programme: Findings from collaborative action research in UK Stop Smoking Services

Background: Within the framework of collaborative action research, the aim was to explore the feasibility of developing and embedding physical activity promotion as a smoking cessation aid within UK 6/7-week National Health Service (NHS) Stop Smoking Services. Methods: In Phase 1 three initial cycles of collaborative action research (observation, reflection, planning, implementation and re-evaluation), in an urban Stop Smoking Service, led to the development of an integrated intervention in which physical activity was promoted as a cessation aid, with the support of a theoretically based self-help guide, and self monitoring using pedometers. In Phase 2 advisors underwent training and offered the intervention, and changes in physical activity promoting behaviour and beliefs were monitored. Also, changes in clients’ stage of readiness to use physical activity as a cessation aid, physical activity beliefs and behaviour and physical activity levels were assessed, among those who attended the clinic at 4-week post-quit. Qualitative data were collected, in the form of clinic observation, informal interviews with advisors and field notes. Results: The integrated intervention emerged through cycles of collaboration as something quite different to previous practice. Based on field notes, there were many positive elements associated with the integrated intervention in Phase 2. Self-reported advisors’ physical activity promoting behaviour increased as a result of training and adapting to the intervention. There was a significant advancement in clients’ stage of readiness to use physical activity as a smoking cessation aid. Conclusions: Collaboration with advisors was key in ensuring that a feasible intervention was developed as an aid to smoking cessation. There is scope to further develop tailored support to increasing physical activity and smoking cessation, mediated through changes in perceptions about the benefits of, and confidence to do physical activity

Abnormal ECG Findings in Athletes: Clinical Evaluation and Considerations.

PURPOSE OF REVIEW: Pre-participation cardiovascular evaluation with electrocardiography is normal practice for most sporting bodies. Awareness about sudden cardiac death in athletes and recognizing how screening can help identify vulnerable athletes have empowered different sporting disciplines to invest in the wellbeing of their athletes. RECENT FINDINGS: Discerning physiological electrical alterations due to athletic training from those representing cardiac pathology may be challenging. The mode of investigation of affected athletes is dependent on the electrical anomaly and the disease(s) in question. This review will highlight specific pathological ECG patterns that warrant assessment and surveillance, together with an in-depth review of the recommended algorithm for evaluation