Large-scale migration into Britain during the Middle to Late Bronze Age.

Present-day people from England and Wales have more ancestry derived from early European farmers (EEF) than did people of the Early Bronze Age1. To understand this, here we generated genome-wide data from 793 individuals, increasing data from the Middle to the Late Bronze Age and Iron Age in Britain by 12-fold, and western and central Europe by 3.5-fold. Between 1000 and 875 BC, EEF ancestry increased in southern Britain (England and Wales) but not northern Britain (Scotland) due to incorporation of migrants who arrived at this time and over previous centuries, and who were genetically most similar to ancient individuals from France. These migrants contributed about half the ancestry of people of England and Wales from the Iron Age, thereby creating a plausible vector for the spread of early Celtic languages into Britain. These patterns are part of a broader trend of EEF ancestry becoming more similar across central and western Europe in the Middle to the Late Bronze Age, coincident with archaeological evidence of intensified cultural exchange2-6. There was comparatively less gene flow from continental Europe during the Iron Age, and the independent genetic trajectory in Britain is also reflected in the rise of the allele conferring lactase persistence to approximately 50% by this time compared to approximately 7% in central Europe where it rose rapidly in frequency only a millennium later. This suggests that dairy products were used in qualitatively different ways in Britain and in central Europe over this period.

The Beaker phenomenon and the genomic transformation of northwest Europe.

From around 2750 to 2500 bc, Bell Beaker pottery became widespread across western and central Europe, before it disappeared between 2200 and 1800 bc. The forces that propelled its expansion are a matter of long-standing debate, and there is support for both cultural diffusion and migration having a role in this process. Here we present genome-wide data from 400 Neolithic, Copper Age and Bronze Age Europeans, including 226 individuals associated with Beaker-complex artefacts. We detected limited genetic affinity between Beaker-complex-associated individuals from Iberia and central Europe, and thus exclude migration as an important mechanism of spread between these two regions. However, migration had a key role in the further dissemination of the Beaker complex. We document this phenomenon most clearly in Britain, where the spread of the Beaker complex introduced high levels of steppe-related ancestry and was associated with the replacement of approximately 90% of Britain's gene pool within a few hundred years, continuing the east-to-west expansion that had brought steppe-related ancestry into central and northern Europe over the previous centuries.

Erratum: The Beaker phenomenon and the genomic transformation of northwest Europe.

This corrects the article DOI: 10.1038/nature25738.

Crisis responses, opportunity, and public authority during Covid-19's first wave in Uganda, the Democratic Republic of Congo, and South Sudan.

Discussions on African responses to Covid-19 have focused on the state and its international backers. Far less is known about a wider range of public authorities, including chiefs, humanitarians, criminal gangs, and armed groups. This paper investigates how the pandemic provided opportunities for claims to and contests over power in Uganda, the Democratic Republic of the Congo, and South Sudan. Ethnographic research is used to contend that local forms of public authority can be akin to miniature sovereigns, able to interpret dictates, policies, and advice as required. Alongside coping with existing complex protracted emergencies, many try to advance their own agendas and secure benefits. Those they seek to govern, though, do not passively accept the new normal, instead often challenging those in positions of influence. This paper assesses which of these actions and reactions will have lasting effects on local notions of statehood and argues for a public authorities lens in times of crisis.

Increased expression of plasminogen activator inhibitor-1 (PAI-1) is associated with depression and depressive phenotype in C57Bl/6J mice.

Plasminogen activator inhibitor 1 (PAI-1), which is elevated in numerous disease states, has been implicated as a stress-related protein involved in the pathogenesis of depression. We measured PAI-1 in the plasma of healthy and depressed individuals and assessed plasminogen activator (PA) expression and regulation by PAI-1 in cultured normal human astrocytes (NHA). Elevated plasma PAI-1 levels were found in depressed patients. Brain tissues from depressed individuals also showed stronger expression of hippocampal PAI-1 by confocal imaging in comparison to healthy individuals. Using a lipopolysaccharide-induced inflammatory model of depression in mice, we measured PAI-1 in murine plasma and brain, by ELISA and immunohistochemistry, respectively. Similar elevations were seen in plasma but not in brain homogenates of mice exposed to LPS. We further correlated the findings with depressive behavior. Ex vivo experiments with NHA treated with proinflammatory cytokines implicated in the pathogenesis of depression showed increased PAI-1 expression. Furthermore, these studies suggest that urokinase-type plasminogen activator may serve as an astrocyte PA reservoir, able to promote cleavage of brain-derived neurotrophic factor (BDNF) during stress or inflammation. In summary, our findings confirm that derangements of PAI-1 variably occur in the brain in association with the depressive phenotype. These derangements may impede the availability of active, mature (m)BDNF and thereby promote a depressive phenotype.

DEWORMING DELUSIONS? MASS DRUG ADMINISTRATION IN EAST AFRICAN SCHOOLS.

Recent debates about deworming school-aged children in East Africa have been described as the 'Worm Wars'. The stakes are high. Deworming has become one of the top priorities in the fight against infectious diseases. Staff at the World Health Organization, the Gates Foundation and the World Bank (among other institutions) have endorsed the approach, and school-based treatments are a key component of large-scale mass drug administration programmes. Drawing on field research in Uganda and Tanzania, and engaging with both biological and social evidence, this article shows that assertions about the effects of school-based deworming are over-optimistic. The results of a much-cited study on deworming Kenyan school children, which has been used to promote the intervention, are flawed, and a systematic review of randomized controlled trials demonstrates that deworming is unlikely to improve overall public health. Also, confusions arise by applying the term deworming to a variety of very different helminth infections and to different treatment regimes, while local-level research in schools reveals that drug coverage usually falls below target levels. In most places where data exist, infection levels remain disappointingly high. Without indefinite free deworming, any declines in endemicity are likely to be reversed. Moreover, there are social problems arising from mass drug administration that have generally been ignored. Notably, there are serious ethical and practical issues arising from the widespread practice of giving tablets to children without actively consulting parents. There is no doubt that curative therapy for children infected with debilitating parasitic infections is appropriate, but overly positive evaluations of indiscriminate deworming are counter-productive.

NEGLECTED TROPICAL DISEASES IN BIOSOCIAL PERSPECTIVE.

The term 'neglected tropical diseases' (NTDs) points to the need for a biosocial perspective. Although 'diseases' are widely understood as biological phenomena, 'neglect' is inherently social. Social priorities, social relations and social behaviour profoundly influence the design, implementation and evaluation of control programmes. Yet, these dimensions of neglect are, themselves, neglected. Instead, emphasis is being placed on preventive chemotherapy - a technical, context-free approach which relies almost entirely on the mass distribution of drugs, at regular intervals, to populations living in endemic areas. This article reflects on the processes which have enabled an NTD 'brand' identity to emerge, and it comments on a disquieting disengagement with some of the more critical insights about the consequences of mass drug administration. Building on the work of biosocial scholars studying other aspects of health and disease, a more adequate, evidence-based approach is delineated. Developing such an approach is an iterative process, requiring on-going engagement with both biological and social insights as they emerge. Considerable theoretical, methodological and political challenges lie ahead, but it is essential they are overcome, if the sustainable control of NTDs is to become a reality.

Will mass drug administration eliminate lymphatic filariasis? Evidence from northern coastal Tanzania.

This article documents understandings and responses to mass drug administration (MDA) for the treatment and prevention of lymphatic filariasis among adults and children in northern coastal Tanzania from 2004 to 2011. Assessment of village-level distribution registers, combined with self-reported drug uptake surveys of adults, participant observation and interviews, revealed that at study sites in Pangani and Muheza districts the uptake of drugs was persistently low. The majority of people living at these highly endemic locations either did not receive or actively rejected free treatment. A combination of social, economic and political reasons explain the low uptake of drugs. These include a fear of treatment (attributable, in part, to a lack of trust in international aid and a questioning of the motives behind the distribution); divergence between biomedical and local understandings of lymphatic filariasis; and limited and ineffective communication about the rationale for mass treatment. Other contributory factors are the reliance upon volunteers for distribution within villages and, in some locations, strained relationships between different groups of people within villages as well as between local leaders and government officials. The article also highlights a disjuncture between self-reported uptake of drugs by adults at a village level and the higher uptake of drugs recorded in official reports. The latter informs claims that elimination will be a possibility by 2020. This gives voice to a broader problem: there is considerable pressure for those implementing MDA to report positive results. The very real challenges of making MDA work are pushed to one side - adding to a rhetoric of success at the expense of engaging with local realities. It is vital to address the kind of issues raised in this article if current attempts to eliminate lymphatic filariasis in mainland coastal Tanzania are to achieve their goal.

Defining competency-based evaluation objectives in family medicine: communication skills.

OBJECTIVE: To provide a pragmatic approach to the evaluation of communication skills using observable behaviours, as part of a multiyear project to develop competency-based evaluation objectives for Certification in family medicine. DESIGN: A nominal group technique was used to develop themes and subthemes and to identify positive and negative observable behaviours that demonstrate competence in communication in family medicine. SETTING: The College of Family Physicians of Canada in Mississauga, Ont. PARTICIPANTS: An expert group of 7 family physicians and 1 educational consultant, all of whom had experience in assessing competence in family medicine. Group members represented the Canadian context with respect to region, sex, language, community type, and experience. METHODS: The group used the nominal group technique to derive a list of observable behaviours that would constitute a detailed operational definition of competence in communication skills; multiple iterations were used until saturation was achieved. The group met several times a year, and membership remained unchanged during the 4 years in which the work was conducted. The iterative process was undertaken twice--once for communication with patients and once for communication with colleagues. MAIN FINDINGS: Five themes, 5 subthemes, and 106 positive and negative observable behaviours were generated. The subtheme of charting skills was defined using a key-features analysis. CONCLUSION: Communication skills were defined in terms of themes and observable behaviours. These definitions were intended to help assess family physicians' competence at the start of independent practice.

Defining competency-based evaluation objectives in family medicine: professionalism.

OBJECTIVE: To develop and describe observable evaluation objectives for assessing competence in professionalism, which are grounded in the experience of practising physicians. DESIGN: Modified nominal group technique. SETTING: The College of Family Physicians of Canada in Mississauga, Ont. PARTICIPANTS: An expert group of 7 family physicians and 1 educational consultant, all of whom had experience in assessing competence in family medicine. Group members represented the Canadian context with respect to region, sex, language, community type, and experience. METHODS: Using an iterative process, the expert group defined a list of observable behaviours that are indicative of professionalism, or not, in the family medicine setting. Themes relate to professional behaviour in family medicine; specific observable behaviours are those that family physicians believe are indicative of professionalism for each theme. MAIN FINDINGS: The expert group identified 12 themes and 140 specific observable behaviours to assist in the observation and discussion of professional behaviour in family medicine workplace settings. CONCLUSION: Competency-based education literature emphasizes the importance of formative evaluation and feedback. Such feedback is particularly challenging in the domain of professionalism because of its personal nature and the potential for emotional reactions. Effective dialogue between learners and teachers begins with clear expectations and reference to descriptions of relevant, specific behaviour. This research has generated a competency-based resource to assist the assessment of professional behaviour in family medicine educational programs.

Defining competency-based evaluation objectives in family medicine: procedure skills.

OBJECTIVE: To develop evaluation objectives for assessing competence in procedure skills using a key-features approach. This was part of a multiyear project to develop competency-based evaluation objectives for Certification in Family Medicine. DESIGN: Nominal group technique. SETTING: The College of Family Physicians of Canada in Mississauga, Ont. PARTICIPANTS: An expert group of 7 family physicians and 1 educational consultant, all of whom had experience in assessing competence in family medicine. Group members represented the Canadian context with respect to region, sex, language, community type, and experience. METHODS: Using a nominal group technique, the expert group developed the general key features for procedure skills. The expert group also linked the key features to already established skill dimensions in the domain of competence, to the 4 principles of family medicine, and to the CanMEDS roles. MAIN FINDINGS: The general key features were developed after 5 iterations. Ten key features were outlined and were shown to reflect all the essential skill dimensions in the domain of competence for family medicine. The key features were linked to 2 of the 4 principles of family medicine and to 4 of the CanMEDS roles. CONCLUSION: The general key features for procedure skills were developed to assess competence in procedure skills in family medicine.

Shifting the dynamics: implementation of locally driven, mixed-methods modelling to inform schistosomiasis control and elimination activities.

INTRODUCTION: The integration of more diverse perspectives into the development of evidence for decision-making has been elusive, despite years of rhetoric to the contrary. This has led to cycles of population-based health interventions which have not delivered the promised results. The WHO most recently set a target for schistosomiasis elimination by 2030 and called for cross-cutting approaches to be driven by endemic countries themselves. The extent to which elimination is feasible within the time frame has been a subject of debate. METHODS: Systems maps were developed through participatory modelling activities with individuals working on schistosomiasis control and elimination activities from the village through national levels in Uganda. These maps were first synthesised, then used to frame the form and content of subsequent mathematical modelling activities, and finally explicitly informed model parameter specifications for simulations, using the open-source SCHISTOX model, driven by the participants. RESULTS: Based on the outputs of the participatory modelling, the simulation activities centred around reductions in water contact. The results of the simulations showed that mass drug administration, at either the current or target levels of coverage, combined with water contact reduction activities, achieved morbidity control in high prevalence Schistosoma mansoni settings, while both morbidity control and elimination were achieved in high prevalence S. haematobium settings within the 10-year time period. CONCLUSION: The combination of participatory systems mapping and individual-based modelling was a rich strategy which explicitly integrated the perspectives of national and subnational policymakers and practitioners into the development of evidence. This strategy can serve as a method by which individuals who have not been traditionally included in modelling activities, and do not hold positions or work in traditional centres of power, may be heard and truly integrated into the development of evidence for decision-making in global health.

Epidemics and the Military: Responding to COVID-19 in Uganda.

The UN Security Council's response to Ebola in 2014 legitimised militarised responses. It also influenced responses to COVID-19 in some African countries. Yet, little is known about the day-to-day impacts for ordinary citizens of mobilising armies for epidemic control. Drawing on 18 months ethnographic research, this article analyses militarised responses to COVID-19 during, and following, two lockdowns at contrasting sites in Uganda: a small town in Pakwach district and a village in Kasese district. Both field sites lie close to the border of the Democratic Republic of Congo. Although the practice of health security varied between sites, the militarised response had more impact than the disease in these two places. The armed forces scaled back movement from urban conurbations to rural and peri-urban areas; while simultaneously enabling locally based official public authorities to use the proclaimed priorities of President Museveni's government to enhance their position and power. This led to a situation whereby inhabitants created new modes of mutuality to resist or subvert the regulations being enforced, including the establishment of new forms of cross-border movement. These findings problematise the widely held view that Uganda's response to COVID-19 was successful. Overall, it is argued that the on-going securitisation of global health has helped to create the political space to militarise the response. While this has had unknown effects on the prevalence of COVID-19, it has entrenched unaccountable modes of public authority and created a heightened sense of insecurity on the ground. The tendency to condone the violent practice of militarised public health programmes by international and national actors reflects a broader shift in the acceptance of more authoritarian forms of governance.

Does mass drug administration for the integrated treatment of neglected tropical diseases really work? Assessing evidence for the control of schistosomiasis and soil-transmitted helminths in Uganda.

BACKGROUND: Less is known about mass drug administration [MDA] for neglected tropical diseases [NTDs] than is suggested by those so vigorously promoting expansion of the approach. This paper fills an important gap: it draws upon local level research to examine the roll out of treatment for two NTDs, schistosomiasis and soil-transmitted helminths, in Uganda. METHODS: Ethnographic research was undertaken over a period of four years between 2005-2009 in north-west and south-east Uganda. In addition to participant observation, survey data recording self-reported take-up of drugs for schistosomiasis, soil-transmitted helminths and, where relevant, lymphatic filariasis and onchocerciasis was collected from a random sample of at least 10% of households at study locations. Data recording the take-up of drugs in Ministry of Health registers for NTDs were analysed in the light of these ethnographic and social survey data. RESULTS: The comparative analysis of the take-up of drugs among adults revealed that although most long term residents have been offered treatment at least once since 2004, the actual take up of drugs for schistosomiasis and soil-transmitted helminths varies considerably from one district to another and often also within districts. The specific reasons why MDA succeeds in some locations and falters in others relates to local dynamics. Issues such as population movement across borders, changing food supply, relations between drug distributors and targeted groups, rumours and conspiracy theories about the 'real' purpose of treatment, subjective experiences of side effects from treatment, alternative understandings of affliction, responses to social control measures and historical experiences of public health control measures, can all make a huge difference. The paper highlights the need to adapt MDA to local circumstances. It also points to specific generalisable issues, notably with respect to health education, drug distribution and more effective use of existing public health legislation. CONCLUSION: While it has been an achievement to have offered free drugs to so many adults, current standard practices of monitoring, evaluation and delivery of MDA for NTDs are inconsistent and inadequate. Efforts to integrate programmes have exacerbated the difficulties. Improved assessment of what is really happening on the ground will be an essential step in achieving long-term overall reduction of the NTD burden for impoverished communities.

Defining competency-based evaluation objectives in family medicine: dimensions of competence and priority topics for assessment.

OBJECTIVE: To develop a definition of competence in family medicine sufficient to guide a review of Certification examinations by the Board of Examiners of the College of Family Physicians of Canada. DESIGN: Delphi analysis of responses to a 4-question postal survey. SETTING: Canadian family practice. PARTICIPANTS: A total of 302 family physicians who have served as examiners for the College of Family Physicians of Canada's Certification examination. METHODS: A survey comprising 4 short-answer questions was mailed to the 302 participating family physicians asking them to list elements that define competence in family medicine among newly certified family physicians beginning independent practice. Two expert groups used a modified Delphi consensus process to analyze responses and generate 2 basic components of this definition of competence: first, the problems that a newly practising family physician should be competent to handle; second, the qualities, behaviour, and skills that characterize competence at the start of independent practice. MAIN FINDINGS: Response rate was 54%; total number of elements among all responses was 5077, for an average 31 per respondent. Of the elements, 2676 were topics or clinical situations to be dealt with; the other 2401 were skills, behaviour patterns, or qualities, without reference to a specific clinical problem. The expert groups identified 6 essential skills, the phases of the clinical encounter, and 99 priority topics as the descriptors used by the respondents. More than 20% of respondents cited 30 of the topics. CONCLUSION: Family physicians define the domain of competence in family medicine in terms of 6 essential skills, the phases of the clinical encounter, and priority topics. This survey represents the first level of definition of evaluation objectives in family medicine. Definition of the interactions among these elements will permit these objectives to become detailed enough to effectively guide assessment.

Defining competency-based evaluation objectives in family medicine: key-feature approach.

OBJECTIVE: To develop key features for priority topics previously identified by the College of Family Physicians of Canada that, together with skill dimensions and phases of the clinical encounter, broadly describe competence in family medicine. DESIGN: Modified nominal group methodology, which was used to develop key features for each priority topic through an iterative process. SETTING: The College of Family Physicians of Canada. PARTICIPANTS: An expert group of 7 family physicians and 1 educational consultant, all of whom had experience in assessing competence in family medicine. Group members represented the Canadian family medicine context with respect to region, sex, language, community type, and experience. METHODS: The group used a modified Delphi process to derive a detailed operational definition of competence, using multiple iterations until consensus was achieved for the items under discussion. The group met 3 to 4 times a year from 2000 to 2007. MAIN FINDINGS: The group analyzed 99 topics and generated 773 key features. There were 2 to 20 (average 7.8) key features per topic; 63% of the key features focused on the diagnostic phase of the clinical encounter. CONCLUSION: This project expands previous descriptions of the process of generating key features for assessment, and removes this process from the context of written examinations. A key-features analysis of topics focuses on higher-order cognitive processes of clinical competence. The project did not define all the skill dimensions of competence to the same degree, but it clearly identified those requiring further definition. This work generates part of a discipline-specific, competency-based definition of family medicine for assessment purposes. It limits the domain for assessment purposes, which is an advantage for the teaching and assessment of learners. A validation study on the content of this work would ensure that it truly reflects competence in family medicine.

Legacies of humanitarian neglect: long term experiences of children who returned from the Lord's Resistance Army in Uganda.

BACKGROUND: Much has been written about the short-term challenges facing children returning 'home' from rebel fighting groups, but little is known about the longer term day to day realities of return. This article presents findings from the first long-term assessment of the social and economic challenges facing an officially registered group of children who passed through an internationally-financed reception centre after a period of time with the Lord's Resistance Army (LRA). METHODS: Records from a reception centre were used to trace a random sample of individuals to their current location. Two hundred and thirty in-depth semi-structured interviews were carried out and 40 follow-up interviews between 2013 and 2016. Interviews were informed by long-term ethnographic research in the region. These interviews were subsequently coded and analysed to describe the long-term day to day realities of return. RESULTS: At the time of interview, 90% of formerly abducted people returned 'home' six or more years ago, and 75% returned nine or more years ago. The majority have managed to access family land for farming, but concerns about what they may have done to survive whilst living with the LRA adversely affects their day-to-day lives. However, some important differences were noted: those men and women who spent less time with the LRA are more likely to live on ancestral land with close relatives; and they are more likely to report experiencing stigma and a spiritual affliction called 'cen'. In contrast, those who spent the longest time with the LRA are less likely to report these problems, they are mainly living in urban locations and tend to manage slightly better. Children born of war are vulnerable to abuse, irrespective of current residence. CONCLUSIONS: Research findings question the merits of post-conflict reintegration programmes emphasising immediate family reunifications, without follow-up monitoring, social protection, education and skills training. By overlooking the diverse experiences of those who lived and fought with the LRA, and failing to anticipate or respond to the long term socio-political and economic challenges facing children on their return, reception centre processes not only failed to foster social reintegration, but they also inadvertently exacerbated the vulnerability of returning children.

Ebola and Public Authority: Saving Loved Ones in Sierra Leone.

It is unclear how public authorities shaped responses to Ebola in Sierra Leone. Focusing on one village, we analyze what happened when "staff, stuff, space, and systems" were absent. Mutuality between neighbors, linked to secret societies, necessitated collective care for infected loved ones, irrespective of the risks. Practical learning was quick. Numbers recovering were reported to be higher among people treated in hidden locations, compared to those taken to Ebola Treatment Centres. Our findings challenge positive post-Ebola narratives about international aid and military deployment. A morally appropriate people's science emerged under the radar of external scrutiny, including that of a paramount chief.