Project description:Fruit shape is the result of the interaction between genetic, epigenetic, environmental factors and stochastic processes. As a core biological descriptor both for taxonomy and horticulture, the point at which shape stability is reached becomes paramount in apple cultivar identification, and authentication in commerce. Twelve apple cultivars were sampled at regular intervals from anthesis to harvest over two growing seasons. Linear and geometric morphometrics were analysed to establish if and when shape stabilised and whether fruit asymmetry influenced this. Shape stability was detected in seven cultivars, four asymmetric and three symmetric. The remaining five did not stabilise. Shape stability, as defined here, is cultivar-dependent, and when it occurs, it is late in the growing season. Geometric morphometrics detected stability more readily than linear, especially in symmetric cultivars. Key shape features are important in apple marketing, giving the distinctness and apparent uniformity between cultivars expected at point of sale.
Project description:ImportanceAlthough a serious fall injury is often a devastating event, little is known about the course of disability (ie, functional trajectories) before a serious fall injury or the relationship between these trajectories and those that follow the fall.ObjectivesTo identify distinct sets of functional trajectories in the year immediately before and after a serious fall injury, to evaluate the relationship between the prefall and postfall trajectories, and to determine whether these results differed based on the type of injury.Design, setting, and participantsProspective cohort study conducted in greater New Haven, Connecticut, from March 16, 1998, to June 30, 2012, in 754 community-living persons aged 70 years or older who were initially nondisabled in their basic activities of daily living. Of the 130 participants who subsequently sustained a serious fall injury, 62 had a hip fracture and 68 had another fall-related injury leading to hospitalization.Main outcomes and measuresFunctional trajectories, based on 13 basic, instrumental, and mobility activities assessed during monthly interviews, were identified in the year before and the year after the serious fall injury.ResultsBefore the fall, 5 distinct trajectories were identified: no disability in 16 participants (12.3%), mild disability in 34 (26.2%), moderate disability in 34 (26.2%), progressive disability in 23 (17.7%), and severe disability in 23 (17.7%). After the fall, 4 distinct trajectories were identified: rapid recovery in 12 participants (9.2%), gradual recovery in 35 (26.9%), little recovery in 26 (20.0%), and no recovery in 57 (43.8%). For both hip fractures and other serious fall injuries, the probabilities of the postfall trajectories were greatly influenced by the prefall trajectories, such that rapid recovery was observed only among persons who had no disability or mild disability, and a substantive recovery, defined as rapid or gradual, was highly unlikely among those who had progressive or severe disability. The postfall trajectories were consistently worse for hip fractures than for the other serious injuries.Conclusions and relevanceThe functional trajectories before and after a serious fall injury are quite varied but highly interconnected, suggesting that the likelihood of recovery is greatly constrained by the prefall trajectory.
Project description:IntroductionFalls are common post-stroke events but their relationship with healthcare costs is unclear. The aim of this study was to examine the relationship between healthcare costs in the first year after stroke and falls among survivors discharged to the community.Patients and methodsSurvivors of acute stroke with planned home discharges from five large hospitals in Ireland were recruited. Falls and healthcare utilisation data were recorded using inpatient records, monthly calendars and post-discharge interviews. Cost of stroke was estimated for each participant from hospital admission for one year. The association of fall-status with overall cost was tested with multivariable linear regression analysis adjusting for pre-stroke function, stroke severity, age and living situation.ResultsA total of 109 stroke survivors with complete follow-up data (mean age = 68.5 years (SD = 13.5 years)) were included. Fifty-three participants (49%) fell following stroke, of whom 28 (26%) had recurrent falls. Estimated mean total healthcare cost was €20,244 (SD=€23,456). The experience of one fall and recurrent falls was independently associated with higher costs of care (p = 0.02 and p < 0.01, respectively).DiscussionThe observed relationship between falls and cost is likely to be underestimated as aids and adaptions, productivity losses, and nursing home care were not included.ConclusionThis study points at differences across fall-status in several healthcare costs categories, namely the index admission, secondary/tertiary care (including inpatient re-admissions) and allied healthcare. Future research could compare the cost-effectiveness of inpatient versus community-based fall-prevention after stroke. Further studies are also required to inform post-stroke bone-health management and fracture-risk reduction.
Project description:To test whether high levels of reported pride are associated with subsequent falls.Secondary analysis of the English Longitudinal Study of Ageing (ELSA) dataset.Multi-wave longitudinal sample of non-institutionalised older English adults.ELSA cohort of 6415 participants at wave 5 (baseline, 2010/11), of whom 4964 were available for follow-up at wave 7 (follow-up, 2014/15).Self reported pride at baseline (low/moderate/high) and whether the participant had reported having fallen during the two years before follow-up.The findings did not support the contention that "pride comes before a fall." Unadjusted estimates indicate that the odds of reported falls were significantly lower for people with high pride levels compared with those who had low pride (odds ratio 0.69, 95% confidence interval 0.58 to 0.81, P<0.001). This association remained after adjustment for age, sex, household wealth, and history of falls (odds ratio 0.81, 0.68 to 0.97, P<0.05). It was partially attenuated after further adjustment for mobility problems, eyesight problems, the presence of a limiting long term illness, a diagnosis of arthritis or osteoporosis, medication use, cognitive function, and pain and depression (odds ratio 0.86, 0.72 to 1.03, P<0.1). Because the confidence interval exceeded 1 in the final model, it remains possible that pride may not be an independent predictor of falls when known risk factors are considered. People with moderate pride did not have lower odds of having fallen than those with low pride in adjusted models. Participants lost to follow-up did not differ from those retained in terms of key variables, and weighting the analyses to account for selective attrition did not produce different results.Contrary to the well known saying "pride comes before a fall," these findings suggest that pride may actually be a protective factor against falling in older adults. Future studies may seek to investigate the mechanisms underpinning this relation.
Project description:Triple negative breast cancer (TNBC) patients not attaining pathological Complete Response (pCR) after neo-adjuvant chemotherapy (NAC) have poor prognosis. We characterized 19 patients for somatic mutations in primary tumor biopsy and residual disease (RD) at surgery by 409 cancer-related gene sequencing (IonAmpliSeqTM Comprehensive Cancer Panel). A median of four (range 1-66) genes was mutated in each primary tumor biopsy, and the most common mutated gene was TP53 followed by a long tail of low frequency mutations. There were no recurrent mutations significantly associated with pCR. However, half of patients with RD had primary tumor biopsy with mutations in genes related to the immune system compared with none of those achieving pCR. Overall, the number of mutations showed a downward trend in post- as compared to pre-NAC samples. PIK3CA was the most common altered gene after NAC. The mutational profile of TNBC during treatment as inferred from patterns of mutant allele frequencies in matched pre-and post-NAC samples showed that RD harbored alterations of cell cycle progression, PI3K/Akt/mTOR, and EGFR tyrosine kinase inhibitor-resistance pathways. Our findings support the use of targeted-gene sequencing for TNBC therapeutic development, as patients without pCR may present mutations of immune-related pathways in their primary tumor biopsy, or actionable targets in the RD.
Project description:The 2019 novel coronavirus (COVID-19) has quickly become one of the most dire international pandemic crises since the 1918 Spanish flu. Evidence for COVID-19 pharmacological therapies has shown rapid growth and a diverse array of results, but an assessment of the value of each piece of evidence must be reinforced. This article aims to review utilized therapies, the evidence level supporting these therapies, as well as drugs under investigation for the treatment of COVID-19. Primary scrutinized therapies include antiviral regimens, such as remdesivir, hydroxychloroquine/chloroquine, lopinavir/ritonavir, immunomodulating drugs, such as corticosteroids and interleukin (IL) inhibitors, and other therapies including convalescent plasma. Only one therapy, dexamethasone, has shown a mortality benefit in randomized controlled trials and summarized evidence for other therapies show limited positive results. Reviewing these therapies in a historical way shows how limited evidence can drive therapy decisions. A broad summary of available evidence can assist clinicians in a return to hierarchical assessments of evidence which can lead to safer patient outcomes, improved distribution of resources, and better targets for appropriate therapy decisions.
Project description:The third Human Variome Project (HVP) Meeting "Integration and Implementation" was held under UNESCO Patronage in Paris, France, at the UNESCO Headquarters May 10-14, 2010. The major aims of the HVP are the collection, curation, and distribution of all human genetic variation affecting health. The HVP has drawn together disparate groups, by country, gene of interest, and expertise, who are working for the common good with the shared goal of pushing the boundaries of the human variome and collaborating to avoid unnecessary duplication. The meeting addressed the 12 key areas that form the current framework of HVP activities: Ethics; Nomenclature and Standards; Publication, Credit and Incentives; Data Collection from Clinics; Overall Data Integration and Access-Peripheral Systems/Software; Data Collection from Laboratories; Assessment of Pathogenicity; Country Specific Collection; Translation to Healthcare and Personalized Medicine; Data Transfer, Databasing, and Curation; Overall Data Integration and Access-Central Systems; and Funding Mechanisms and Sustainability. In addition, three societies that support the goals and the mission of HVP also held their own Workshops with the view to advance disease-specific variation data collection and utilization: the International Society for Gastrointestinal Hereditary Tumours, the Micronutrient Genomics Project, and the Neurogenetics Consortium.
Project description:Although waterfowl are the primary reservoir for multiple subtypes of influenza A virus (IAV), our understanding of population immunity in naturally infected waterfowl is poorly understood. Population immunity may be an important driver of seasonal subtype predominance in waterfowl populations and may affect the potential for establishment of introduced IAV such as the Eurasian-like A/Goose/Guangdong/1/1996 lineage in these populations. Here, we examine the prevalence of naturally acquired antibodies to nucleoprotein (NP), hemagglutinin (H3, H4, H5), and neuraminidase (N1, N2, N6, N8) in early migrating mallards (Anas platyrhynchos) sampled in Northwest Minnesota during staging and early fall migration in September 2014, 2015, 2017, and 2018. Serologic results were compared to historic and contemporary virus isolation results from these same study sites. The prevalence of antibodies to NP ranged from 60.8-76.1% in hatch-year (HY) birds and from 86.0-92.7% in after-hatch-year (AHY, >1-year-old) mallards indicating a high level of previous infection with IAV early in the fall migration season. Neutralizing antibodies were detected against H3, H4, and H5 in all years as were antibodies to N1, N2, N6, and N8. A high proportion of NP seropositive ducks tested positive for antibodies to multiple HA and NA subtypes, and this was more common in the AHY age class. Antibody prevalence to the HA and NA subtypes included in this study were consistent with the predominance of H4N6 in these populations during all years and reflected a broadening of the antibody response with age. Additional work is needed to document the longevity of these immune responses, if and how they correlate with protection against IAV transmission, infection, and disease, and if, as detected in this study, they adequately describe the true extent of exposure to IAV or specific HA or NA subtypes.
Project description:Sex differences exist in behaviors, disease and neuropsychiatric disorders. Sexual dimorphisms however, have yet to be studied across the whole brain and across a comprehensive time course of postnatal development. Here, we use manganese-enhanced MRI (MEMRI) to longitudinally image male and female C57BL/6J mice across 9 time points, beginning at postnatal day 3. We recapitulate findings on canonically dimorphic areas, demonstrating MEMRI's ability to study neuroanatomical sex differences. We discover, upon whole-brain volume correction, that neuroanatomical regions larger in males develop earlier than those larger in females. Groups of areas with shared sexually dimorphic developmental trajectories reflect behavioral and functional networks, and expression of genes involved with sex processes. Also, post-pubertal neuroanatomy is highly individualized, and individualization occurs earlier in males. Our results demonstrate the ability of MEMRI to reveal comprehensive developmental differences between male and female brains, which will improve our understanding of sex-specific predispositions to various neuropsychiatric disorders.
Project description:The post-fledging period is one of the least studied portions of the annual cycle in waterfowl. Yet, recruitment into the breeding population requires that young birds have sufficient resources to survive this period. We used radio-telemetry and generalized estimating equations to examine support for four hypotheses regarding the drivers of landscape scale habitat use and movements made by juvenile ring-necked ducks between the pre-fledging period and departure for migration. Our response variables included the probability of movement, distances moved, and use of different lake types: brood-rearing lakes, staging lakes, and lakes with low potential for disturbance. Birds increased their use of staging areas and lakes with low potential for disturbance (i.e., without houses or boat accesses, >100 m from roads, or big lakes with areas where birds could sit undisturbed) throughout the fall, but these changes began before the start of the hunting season and their trajectory was not changed by the onset of hunting. Males and females moved similar distances and had similar probabilities of movements each week. However, females were more likely than males to use brood-rearing lakes later in the fall. Our findings suggest juvenile ring-necked ducks require different lake types throughout the fall, and managing solely for breeding habitat will be insufficient for meeting needs during the post-fledging period. Maintaining areas with low potential for disturbance and areas suitable for staging will ensure that ring-necked ducks have access to habitat throughout the fall.