231 research outputs found
Potential gene conversion and source genes for recently integrated Alu elements
Alu elements comprise \u3e10% of the human genome. We have used a computational biology approach to analyze the human genomic DNA sequence databases to determine the impact of gene conversion on the sequence diversity of recently integrated Alu elements and to identify Alu elements that were potentially retroposition competent. We analyzed 269 Alu Ya5 elements and identified 23 members of a new Alu subfamily termed Ya5a2 with an estimated copy number of 35 members, including the de novo Alu insertion in the NFI gene. Our analysis of Alu elements containing one to four (Ya1-Ya4) of the Ya5 subfamily-specific mutations suggests that gene conversion contributed as much as 10%-20% of the variation between recently integrated Alu elements. In addition, analysis of the middle A-rich region of the different Alu Ya5 members indicates a tendency toward expansion of this region and subsequent generation of simple sequence repeats. Mining the databases for putative retroposition-competent elements that share 100% nucleotide identity to the previously reported de novo Alu insertions linked to human diseases resulted in the retrieval of 13 exact matches to the NF1 Alu repeat, three to the Alu element in BRCA2, and one to the Alu element in FGFR2 (Apert syndrome). Transient transfections of the potential source gene for the Apert\u27s Alu with its endogenous flanking genomic sequences demonstrated the transcriptional and presumptive transpositional competency of the element
Genetic Evidence on the Origins of Indian Caste Populations
This is the published version, also available here: http://www.dx.doi.org/10.1101/gr.173301.The origins and affinities of the âŒ1 billion people living on the subcontinent of India have long been contested.
This is owing, in part, to the many different waves of immigrants that have influenced the genetic structure of
India. In the most recent of these waves, Indo-European-speaking people from West Eurasia entered India from
the Northwest and diffused throughout the subcontinent. They purportedly admixed with or displaced
indigenous Dravidic-speaking populations. Subsequently they may have established the Hindu caste system and
placed themselves primarily in castes of higher rank. To explore the impact of West Eurasians on contemporary
Indian caste populations, we compared mtDNA (400 bp of hypervariable region 1 and 14 restriction site
polymorphisms) and Y-chromosome (20 biallelic polymorphisms and 5 short tandem repeats) variation in âŒ265
males from eight castes of different rank to âŒ750 Africans, Asians, Europeans, and other Indians. For maternally
inherited mtDNA, each caste is most similar to Asians. However, 20%â30% of Indian mtDNA haplotypes
belong to West Eurasian haplogroups, and the frequency of these haplotypes is proportional to caste rank, the
highest frequency of West Eurasian haplotypes being found in the upper castes. In contrast, for paternally
inherited Y-chromosome variation each caste is more similar to Europeans than to Asians. Moreover, the
affinity to Europeans is proportionate to caste rank, the upper castes being most similar to Europeans,
particularly East Europeans. These findings are consistent with greater West Eurasian male admixture with castes
of higher rank. Nevertheless, the mitochondrial genome and the Y chromosome each represents only a single
haploid locus and is more susceptible to large stochastic variation, bottlenecks, and selective sweeps. Thus, to
increase the power of our analysis, we assayed 40 independent, biparentally inherited autosomal loci (1 LINE-1
and 39 Alu elements) in all of the caste and continental populations (âŒ600 individuals). Analysis of these data
demonstrated that the upper castes have a higher affinity to Europeans than to Asians, and the upper castes are
significantly more similar to Europeans than are the lower castes. Collectively, all five datasets show a trend
toward upper castes being more similar to Europeans, whereas lower castes are more similar to Asians. We
conclude that Indian castes are most likely to be of proto-Asian origin with West Eurasian admixture resulting
in rank-related and sex-specific differences in the genetic affinities of castes to Asians and Europeans
Time Variation of the Fine Structure Constant Driven by Quintessence
There are indications from the study of quasar absorption spectra that the
fine structure constant may have been measurably smaller for redshifts
Analyses of other data (Sm fission rate for the Oklo natural
reactor, variation of Re -decay rate in meteorite studies,
atomic clock measurements) which probe variations of in the more
recent past imply much smaller deviations from its present value. In this work
we tie the variation of to the evolution of the quintessence field
proposed by Albrecht and Skordis, and show that agreement with all these data,
as well as consistency with WMAP observations, can be achieved for a range of
parameters. Some definite predictions follow for upcoming space missions
searching for violations of the equivalence principle.Comment: Final version, to be published in Phys Rev
Improving the development, monitoring and reporting of stroke rehabilitation research: consensus-based core recommendations from the Stroke Recovery and Rehabilitation Roundtable (SRRR)
Recent reviews have demonstrated that the quality of stroke rehabilitation research has continued to improve over the last four decades but despite this progress there are still many barriers in moving the field forward. Rigorous development, monitoring and complete reporting of interventions in stroke trials are essential in providing rehabilitation evidence that is robust, meaningful and implementable.
An international partnership of stroke rehabilitation experts committed to develop consensus-based core recommendations with a remit of addressing the issues identified as limiting stroke rehabilitation research in the areas of developing, monitoring and reporting stroke rehabilitation interventions. Work exploring each of the three areas took place via multiple teleconferences and a two-day meeting in Philadelphia in May 2016. A total of 15 recommendations were made.
To validate the need for the recommendations the group reviewed all stroke rehabilitation trials published in 2015 (n=182 papers). Our review highlighted that the majority of publications did not clearly describe how interventions were developed or monitored during the trial. In particular, under-reporting of the theoretical rationale for the intervention and the components of the intervention calls into question many interventions that have been evaluated for efficacy. More trials were found to have addressed the reporting of interventions recommendations than those related to development or monitoring. Nonetheless the majority of reporting recommendations were still not adequately described.
To progress the field of stroke rehabilitation research and to ensure stroke patients receive optimal evidence based clinical care we urge the research community to endorse and adopt our recommendations
Using video-reflexive ethnography to capture the complexity of leadership enactment in the healthcare workplace
This research was part of LGâs Ph.D. research which was generously funded by NHS Education for Scotland through SMERC.Current theoretical thinking asserts that leadership should be distributed across many levels of healthcare organisations to improve the patient experience and staff morale. However, much healthcare leadership education focusses on the training and competence of individuals and little attention is paid to the interprofessional workplace and how its inherent complexities might contribute to the emergence of leadership. Underpinned by complexity theory, this research aimed to explore how interprofessional healthcare teams enact leadership at a micro-level through influential acts of organising. A whole (interprofessional) team workplace-based study utilising video-reflexive ethnography occurred in two UK clinical sites. Thematic framework analyses of the video data (video-observation and video-reflexivity sessions) were undertaken, followed by in-depth analyses of humanâhuman and humanâmaterial interactions. Data analysis revealed a complex interprofessional environment where leadership is a dynamic process, negotiated and renegotiated in various ways throughout interactions (both formal and informal). Being able to âseeâ themselves at work gave participants the opportunity to discuss and analyse their everyday leadership practices and challenge some of their sometimes deeply entrenched values, beliefs, practices and assumptions about healthcare leadership. These study findings therefore indicate a need to redefine the way that medical and healthcare educators facilitate leadership development and argue for new approaches to research which shifts the focus from leaders to leadership.Publisher PDFPeer reviewe
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Flexible visiting positively impacted on patients, families and staff in an Australian Intensive Care Unit: A before-after mixed method study
Background
The admission of a relative to intensive care is stressful for families. To help them support the patient, families need assurance, information and an ability to be near their sick relative. Flexible visiting enables patient access but the impact of this on patients, families and staff is not clear.
Objective
To assess the impact of flexible visiting from the perspective of patients, families, and Intensive Care Unit (ICU) staff.
Methods
A before-after mixed method study was used with interviews, focus groups and surveys. Patients were interviewed, family members completed the Family Satisfaction in ICU survey and ICU staff completed a survey and participated in focus groups following the introduction of 21â
h per day visiting in a tertiary ICU. The study was conducted within a philosophy of family-centred care.
Results
All interviewed patients (nâ
=â
12) positively evaluated the concept of extended visiting hours. Family membersâ (nâ
=â
181) overall âsatisfaction with careâ did not change; however 85% were âvery satisfiedâ with increased visiting flexibility. Seventy-six percent of family visits continued to occur within the previous visiting hours (11â
amâ8â
pm) with the remaining 24% taking place during the newly available visiting hours. Families recognised the priority of patient care with their personal needs being secondary. Three-quarters of ICU staff were âsatisfiedâ with flexible visiting and suggested any barriers could be overcome by role modelling family inclusion.
Conclusion
Patients, families and ICU staff positively evaluated flexible visiting hours in this ICU. Although only a minority of families took advantage of the increased hours they indicated appreciation for the additional opportunities. Junior staff may benefit from peer-support to develop family inclusion skills. More flexible visiting times can be incorporated into usual ICU practice in a manner that is viewed positively by all stakeholders
Serum HCoV-spike specific antibodies do not protect against subsequent SARS-CoV-2 infection in children and adolescents
SARS-CoV-2 infections in children are generally asymptomatic or mild and rarely progress to severe disease and hospitalization. Why this is so remains unclear. Here we explore the potential for protection due to pre-existing cross-reactive seasonal coronavirus antibodies and compare the rate of antibody decline for nucleocapsid and spike protein in serum and oral fluid against SARS-CoV-2 within the pediatric population. No differences in seasonal coronaviruses antibody concentrations were found at baseline between cases and controls, suggesting no protective effect from pre-existing immunity against seasonal coronaviruses. Antibodies against seasonal betacoronaviruses were boosted in response to SARS-CoV-2 infection. In serum, anti-nucleocapsid antibodies fell below the threshold of positivity more quickly than anti-spike protein antibodies. These findings add to our understanding of protection against infection with SARS-CoV-2 within the pediatric population, which is important when considering pediatric SARS-CoV-2 immunization policies
Perceived difficulty and appropriateness of decision making by General Practitioners: a systematic review of scenario studies
Background: Health-care quality in primary care depends largely on the appropriateness of General Practitionersâ (GPs; Primary Care or Family Physicians) decisions, which may be influenced by how difficult they perceive decisions to be. Patient scenarios (clinical or case vignettes) are widely used to investigate GPsâ decision making. This review aimed to identify the extent to which perceived decision difficulty, decision appropriateness, and their relationship have been assessed in scenario studies of GPsâ decision making; identify possible determinants of difficulty and appropriateness; and investigate the relationship between difficulty and appropriateness.
Methods: MEDLINE, EMBASE, PsycINFO, the Cochrane Library and Web of Science were searched for scenario studies of GPsâ decision making. One author completed article screening. Ten percent of titles and abstracts were checked by an independent volunteer, resulting in 91% agreement. Data on decision difficulty and appropriateness were extracted by one author and descriptively synthesised. Chi-squared tests were used to explore associations between decision appropriateness, decision type and decision appropriateness assessment method.
Results: Of 152 included studies, 66 assessed decision appropriateness and five assessed perceived difficulty. While no studies assessed the relationship between perceived difficulty and appropriateness, one study objectively varied the difficulty of the scenarios and assessed the relationship between a measure of objective difficulty and appropriateness. Across 38 studies where calculations were possible, 62% of the decisions were appropriate as defined by the appropriateness standard used. Chi-squared tests identified statistically significant associations between decision appropriateness, decision type and decision appropriateness assessment method. Findings suggested a negative relationship between decision difficulty and appropriateness, while interventions may have the potential to reduce perceived difficulty.
Conclusions: Scenario-based research into GPsâ decisions rarely considers the relationship between perceived decision difficulty and decision appropriateness. The links between these decisional components require further investigation
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