Control of Dynamic Stability during Gait Termination on a Slippery Surface

The purpose of this thesis is to investigate the reaction to a purely unexpected slip during gait termination and subsequent experiences stopping on the slippery surface in participants who are young and healthy, older and healthy and who have Parkinson’s disease while on traditional dopamine-replacement medication. Gait termination requires control of the forward momentum of the body’s centre of mass (COM). This forward momentum must be dissipated and the COM held within a newly formed base of support. The challenge of stopping on a slippery surface involves maintaining stability while transitioning from steady-state locomotion to steady-state stance. Experience with a slippery surface changes postural and gait characteristics to diminish the perturbing effect of the slip. The magnitude of the slip response diminishes quickly as the movement becomes more efficient. Our investigations revealed a typical slip response to a purely unexpected slip during gait termination including a lowering of the COM, an increased muscular response to support the body, a shortened step and an arm raise. Knowledge of and experience with the slippery surface quickly changed the slip response to reduce the perturbing effect of the slip and also to increase the efficiency of the response while smoothly transitioning from steady-state locomotion to gait termination. Parkinson’s disease impairs balance control, the ability to switch between motor tasks and also to stop within two steps. The need for a voluntary change in motor programs along with difficulty stopping and increased instability makes gait termination a potentially difficult task for someone with Parkinson’s disease (PD). The participants with PD used a slower, safer strategy to stop on non-slippery surfaces to compensate for their instability compared to age-matched controls. When a slip was first introduced during gait termination, the participants with PD continued to be less stable in the plane of progression than the control group. Despite the instability, the PD group was still able to integrate a balance-correcting response into a voluntary gait termination program. The ability to generate adaptive strategies to integrate the balance-correcting response into a voluntary gait termination program over multiple trials does not appear to be affected by PD; both the control group and PD group showed behavioural modifications according to repeated exposures to the slippery surface. Although participants with PD seemed slightly less stable and walked slower, their behavioural adaptations were similar to the control group

LANDING ASYMMETRY IN BACK TUCKED SALTOS AND THE EFFECT OF TAKEOFF ASYMMETRY

Landing asymmetry is an injury risk factor in gymnastics. This study examined whether takeoff force asymmetry is related to landing asymmetry during back tucked saltos in competitive gymnasts. Each gymnast performed an isometric leg strength test followed by multiple back tucked salto trials with no takeoff instruction, leaning with 60% asymmetry to the right, and 60% asymmetry to the left using a standard asymmetry index. Forces were measured at takeoff and landing. The novel experimental approach successfully produced distinct takeoff asymmetry levels. There was a significant rightward asymmetry in baseline landing peak vertical force, possibly due to right leg strength dominance. Landing asymmetry was also generated in the left and right leaning conditions. Both takeoff and leg strength asymmetries may play a role in landing force asymmetries in back tucked saltos

Evaluating snow microbial assemblages

Psychrophiles are organisms that grow optimally below 20C (1). The US Great Basin is home to many mountain peaks with an abundance of alpine snow environments perfect for psychrophilic habitation. We analyzed samples from three different locations, Wheeler Peak, Pacific Crest Trail, and Mount Conness, characterizing and comparing the psychrophilic communities at varying depth intervals in the snow. Polymerase chain reaction (PCR) and denaturing gradient gel electrophoresis (DGGE) showed no notable difference in community structure with depth, but there was a distinct difference when comparing different snow environments (i.e. shaded vs. full sun exposure). The chlorophyll concentration decreased as the depth of the snow increased. By creating a clone library and utilizing DNA sequencing technology we were able to obtain 16S and 18S rRNA gene sequences from samples collected from Mount Conness, which allowed us to identify microbes living in the ecosystem. This information enabled us to produce bacterial and eukaryl phylogenetic trees, giving us a clear look into the diversity of this psychrophilic community. Out of seventy bacterial results there were fifty‐three ‐Proteobacteria, thirteen Sphingobacteria, and only three Actinobacteria, with one unclassified bacteria as well. These results will guide us in our future plans for experimentation

The measurement properties of the Lean-and-Release test in people with incomplete spinal cord injury or disease

Objective: To evaluate test-retest reliability, agreement, and convergent validity of the Lean-and-Release test for the assessment of reactive stepping among individuals with incomplete spinal cord injury or disease (iSCI/D). Design: Multi-center cross-sectional multiple test design. Setting: SCI/D rehabilitation hospital and biomechanics laboratory. Participants: Individuals with motor incomplete SCI/D (iSCI/D). Interventions: None. Outcome Measures: Twenty-six participants attended two sessions to complete the Lean-and-Release test and a battery of clinical tests. Behavioral (i.e. one-step, multi-step, loss of balance) and temporal (i.e. timing of foot off, foot contact, swing of reactive step) parameters were measured. Test-retest reliability was determined with intraclass correlation coefficients, and agreement was evaluated with Bland–Altman plots. Convergent validity was assessed through correlations with clinical tests. Results: The behavioral responses were reliable for the Lean-and-Release test (ICC = 0.76), but foot contact was the only reliable temporal parameter using data from a single site (ICC = 0.79). All variables showed agreement according to the Bland–Altman plots. The behavioral responses correlated with scores of lower extremity strength (0.54, P\u3c0.01) and balance confidence (0.55, P \u3c 0.01). Swing time of reactive stepping correlated with step time (0.73, P \u3c 0.01) and cadence (−0.73 P \u3c 0.01) of over ground walking. Conclusions: The behavioral response of the Lean-and-Release test is a reliable and valid measure for people with iSCI/D. Our findings support the use of the behavioral responses to evaluate reactive stepping for research and clinical purposes. Trial registration: ClinicalTrials.gov identifier: NCT02960178

Perceptions and experiences of interventions to prevent postnatal depression: a systematic review and qualitative evidence synthesis

Background More women experience depressive symptoms antenatally than postnatally. Supporting women through the antenatal period is recognised as important in mitigating negative outcomes and in preventing postnatal depression (PND). A systematic review was conducted which aimed to provide a detailed service user and service provider perspective on the uptake, acceptability, and perception of harms of antenatal interventions and postnatal interventions for preventing PND. Methods A comprehensive literature search was conducted in 12 major bibliographic databases in November 2012 and updated in December 2014. Studies were included if they contained qualitative evidence on the perspectives and attitudes of pregnant women and postnatal women who had taken part in, or healthcare professionals (HCPs) involved in delivering, preventive interventions for PND. Results Twenty-two studies were included. Support and empowerment through education were identified as particularly helpful to women as intervention components, across all intervention types. Implications for accessing the service, understanding the remit of the service and women's preferences for group and individual care also emerged. Limitations The majority of the included studies were of moderate or low quality, which may result in a lack of rich data consistently across all studies, limiting to some degree interpretations that can be made. Conclusion The synthesis demonstrated important considerations for devising new interventions or adapting existing interventions. Specifically, it is important that individual or group interventions are carefully tailored to women's needs or preferences and women are aware of the remit of the HCPs role to ensure they feel able to access the support required

Efficiency and safety of varying the frequency of whole blood donation (INTERVAL): a randomised trial of 45 000 donors

Background: Limits on the frequency of whole blood donation exist primarily to safeguard donor health. However, there is substantial variation across blood services in the maximum frequency of donations allowed. We compared standard practice in the UK with shorter inter-donation intervals used in other countries. Methods: In this parallel group, pragmatic, randomised trial, we recruited whole blood donors aged 18 years or older from 25 centres across England, UK. By use of a computer-based algorithm, men were randomly assigned (1:1:1) to 12-week (standard) versus 10-week versus 8-week inter-donation intervals, and women were randomly assigned (1:1:1) to 16-week (standard) versus 14-week versus 12-week intervals. Participants were not masked to their allocated intervention group. The primary outcome was the number of donations over 2 years. Secondary outcomes related to safety were quality of life, symptoms potentially related to donation, physical activity, cognitive function, haemoglobin and ferritin concentrations, and deferrals because of low haemoglobin. This trial is registered with ISRCTN, number ISRCTN24760606, and is ongoing but no longer recruiting participants. Findings: 45 263 whole blood donors (22 466 men, 22 797 women) were recruited between June 11, 2012, and June 15, 2014. Data were analysed for 45 042 (99·5%) participants. Men were randomly assigned to the 12-week (n=7452) versus 10-week (n=7449) versus 8-week (n=7456) groups; and women to the 16-week (n=7550) versus 14-week (n=7567) versus 12-week (n=7568) groups. In men, compared with the 12-week group, the mean amount of blood collected per donor over 2 years increased by 1·69 units (95% CI 1·59–1·80; approximately 795 mL) in the 8-week group and by 0·79 units (0·69–0·88; approximately 370 mL) in the 10-week group (p<0·0001 for both). In women, compared with the 16-week group, it increased by 0·84 units (95% CI 0·76–0·91; approximately 395 mL) in the 12-week group and by 0·46 units (0·39–0·53; approximately 215 mL) in the 14-week group (p<0·0001 for both). No significant differences were observed in quality of life, physical activity, or cognitive function across randomised groups. However, more frequent donation resulted in more donation-related symptoms (eg, tiredness, breathlessness, feeling faint, dizziness, and restless legs, especially among men [for all listed symptoms]), lower mean haemoglobin and ferritin concentrations, and more deferrals for low haemoglobin (p<0·0001 for each) than those observed in the standard frequency groups. Interpretation: Over 2 years, more frequent donation than is standard practice in the UK collected substantially more blood without having a major effect on donors' quality of life, physical activity, or cognitive function, but resulted in more donation-related symptoms, deferrals, and iron deficiency. Funding: NHS Blood and Transplant, National Institute for Health Research, UK Medical Research Council, and British Heart Foundation

Attention bias to emotional faces varies by IQ and anxiety in Williams syndrome

Individuals with Williams syndrome (WS) often experience significant anxiety. A promising approach to anxiety intervention has emerged from cognitive studies of attention bias to threat. To investigate the utility of this intervention in WS, this study examined attention bias to happy and angry faces in individuals with WS (N=46). Results showed a significant difference in attention bias patterns as a function of IQ and anxiety. Individuals with higher IQ or higher anxiety showed a significant bias toward angry, but not happy faces, whereas individuals with lower IQ or lower anxiety showed the opposite pattern. These results suggest that attention bias interventions to modify a threat bias may be most effectively targeted to anxious individuals with WS with relatively high IQ

Longer-term efficiency and safety of increasing the frequency of whole blood donation (INTERVAL): extension study of a randomised trial of 20 757 blood donors

Background: The INTERVAL trial showed that, over a 2-year period, inter-donation intervals for whole blood donation can be safely reduced to meet blood shortages. We extended the INTERVAL trial for a further 2 years to evaluate the longer-term risks and benefits of varying inter-donation intervals, and to compare routine versus more intensive reminders to help donors keep appointments. Methods: The INTERVAL trial was a parallel group, pragmatic, randomised trial that recruited blood donors aged 18 years or older from 25 static donor centres of NHS Blood and Transplant across England, UK. Here we report on the prespecified analyses after 4 years of follow-up. Participants were whole blood donors who agreed to continue trial participation on their originally allocated inter-donation intervals (men: 12, 10, and 8 weeks; women: 16, 14, and 12 weeks). They were further block-randomised (1:1) to routine versus more intensive reminders using computer-generated random sequences. The prespecified primary outcome was units of blood collected per year analysed in the intention-to-treat population. Secondary outcomes related to safety were quality of life, self-reported symptoms potentially related to donation, haemoglobin and ferritin concentrations, and deferrals because of low haemoglobin and other factors. This trial is registered with ISRCTN, number ISRCTN24760606, and has completed. Findings: Between Oct 19, 2014, and May 3, 2016, 20 757 of the 38 035 invited blood donors (10 843 [58%] men, 9914 [51%] women) participated in the extension study. 10 378 (50%) were randomly assigned to routine reminders and 10 379 (50%) were randomly assigned to more intensive reminders. Median follow-up was 1·1 years (IQR 0·7–1·3). Compared with routine reminders, more intensive reminders increased blood collection by a mean of 0·11 units per year (95% CI 0·04–0·17; p=0·0003) in men and 0·06 units per year (0·01–0·11; p=0·0094) in women. During the extension study, each week shorter inter-donation interval increased blood collection by a mean of 0·23 units per year (0·21–0·25) in men and 0·14 units per year (0·12–0·15) in women (both p<0·0001). More frequent donation resulted in more deferrals for low haemoglobin (odds ratio per week shorter inter-donation interval 1·19 [95% CI 1·15–1·22] in men and 1·10 [1·06–1·14] in women), and lower mean haemoglobin (difference per week shorter inter-donation interval −0·84 g/L [95% CI −0·99 to −0·70] in men and −0·45 g/L [–0·59 to −0·31] in women) and ferritin concentrations (percentage difference per week shorter inter-donation interval −6·5% [95% CI −7·6 to −5·5] in men and −5·3% [–6·5 to −4·2] in women; all p<0·0001). No differences were observed in quality of life, serious adverse events, or self-reported symptoms (p>0.0001 for tests of linear trend by inter-donation intervals) other than a higher reported frequency of doctor-diagnosed low iron concentrations and prescription of iron supplements in men (p<0·0001). Interpretation: During a period of up to 4 years, shorter inter-donation intervals and more intensive reminders resulted in more blood being collected without a detectable effect on donors' mental and physical wellbeing. However, donors had decreased haemoglobin concentrations and more self-reported symptoms compared with the initial 2 years of the trial. Our findings suggest that blood collection services could safely use shorter donation intervals and more intensive reminders to meet shortages, for donors who maintain adequate haemoglobin concentrations and iron stores. Funding: NHS Blood and Transplant, UK National Institute for Health Research, UK Medical Research Council, and British Heart Foundation

Mortality Among Adults With Cancer Undergoing Chemotherapy or Immunotherapy and Infected With COVID-19

Importance: Large cohorts of patients with active cancers and COVID-19 infection are needed to provide evidence of the association of recent cancer treatment and cancer type with COVID-19 mortality. // Objective: To evaluate whether systemic anticancer treatments (SACTs), tumor subtypes, patient demographic characteristics (age and sex), and comorbidities are associated with COVID-19 mortality. // Design, Setting, and Participants: The UK Coronavirus Cancer Monitoring Project (UKCCMP) is a prospective cohort study conducted at 69 UK cancer hospitals among adult patients (≥18 years) with an active cancer and a clinical diagnosis of COVID-19. Patients registered from March 18 to August 1, 2020, were included in this analysis. // Exposures: SACT, tumor subtype, patient demographic characteristics (eg, age, sex, body mass index, race and ethnicity, smoking history), and comorbidities were investigated. // Main Outcomes and Measures: The primary end point was all-cause mortality within the primary hospitalization. // Results: Overall, 2515 of 2786 patients registered during the study period were included; 1464 (58%) were men; and the median (IQR) age was 72 (62-80) years. The mortality rate was 38% (966 patients). The data suggest an association between higher mortality in patients with hematological malignant neoplasms irrespective of recent SACT, particularly in those with acute leukemias or myelodysplastic syndrome (OR, 2.16; 95% CI, 1.30-3.60) and myeloma or plasmacytoma (OR, 1.53; 95% CI, 1.04-2.26). Lung cancer was also significantly associated with higher COVID-19–related mortality (OR, 1.58; 95% CI, 1.11-2.25). No association between higher mortality and receiving chemotherapy in the 4 weeks before COVID-19 diagnosis was observed after correcting for the crucial confounders of age, sex, and comorbidities. An association between lower mortality and receiving immunotherapy in the 4 weeks before COVID-19 diagnosis was observed (immunotherapy vs no cancer therapy: OR, 0.52; 95% CI, 0.31-0.86). // Conclusions and Relevance: The findings of this study of patients with active cancer suggest that recent SACT is not associated with inferior outcomes from COVID-19 infection. This has relevance for the care of patients with cancer requiring treatment, particularly in countries experiencing an increase in COVID-19 case numbers. Important differences in outcomes among patients with hematological and lung cancers were observed

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder