Detecting T-cell clonal expansions and quantifying clone survival using deep profiling of immune repertoires.

An individual's T-cell repertoire constantly changes under the influence of external and internal factors. Cells that do not receive a stimulatory signal die, while those that encounter and recognize a pathogen or receive a co-stimulatory signal divide, resulting in clonal expansions. T-cell clones can be traced by monitoring the presence of their unique T-cell receptor (TCR) sequence, which is assembled de novo through a process known as V(D)J rearrangement. Tracking T cells can provide valuable insights into the survival of cells after hematopoietic stem cell transplantation (HSCT) or cancer treatment response and can indicate the induction of protective immunity by vaccination. In this study, we report a bioinformatic method for quantifying the T-cell repertoire dynamics from TCR sequencing data. We demonstrate its utility by measuring the T-cell repertoire stability in healthy donors, by quantifying the effect of donor lymphocyte infusion (DLI), and by tracking the fate of the different T-cell subsets in HSCT patients and the expansion of pathogen-specific clones in vaccinated individuals.

Weights, resistance bands, and rest days are best for tendinopathy.

The studyPavlova AV, Shim JSC, Moss R, et al. Effect of resistance exercise dose components for tendinopathy management: a systematic review with meta-analysis. Br J Sports Med 2023;57:1327-34.To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/weights-resistance-bands-rest-days-best-tendinopathy/.

A Spin Valve-Based Rhombus-Shaped Micro-Object Implementing a Full Wheatstone Bridge.

Spin valves with a synthetic antiferromagnet were fabricated via magnetron sputtering. It was shown that the fabricated spin valve layers had a perfect microstructure and smooth interfaces, and therefore, an RKKY interaction dominated in the coupling of the ferromagnetic layers separated by a copper spacer. Rhombus-shaped micro-objects were fabricated from a single spin valve film. The thermomagnetic treatment procedure was found to form unidirectional anisotropy in the micro-object such that the values of the exchange bias fields in the rhombus' nonparallel sides were opposite in sign. For the CoFeNi/Ru/CoFeNi synthetic antiferromagnet, we determined the differences between the ferromagnetic layer thicknesses at which the thermomagnetic treatment formed the same exchange bias all over each rhombus' side. We also fabricated a sensor element in which each side of the rhombus was the shoulder of a Wheatstone bridge. After the thermomagnetic treatment procedure, each shoulder worked as an active magnetosensitive element, enabling the device to operate as a full Wheatstone bridge. The sensor output exhibited a step shape, high sensitivity to field changes, and significant magnetic hysteresis. Such characteristics are suitable for switching devices.

Exercise therapy for tendinopathy: a mixed-methods evidence synthesis exploring feasibility, acceptability and effectiveness.

Background: Tendinopathy is a common, painful and functionally limiting condition, primarily managed conservatively using exercise therapy. Review questions: (i) What exercise interventions have been reported in the literature for which tendinopathies? (ii) What outcomes have been reported in studies investigating exercise interventions for tendinopathy? (iii) Which exercise interventions are most effective across all tendinopathies? (iv) Does type/location of tendinopathy or other specific covariates affect which are the most effective exercise therapies? (v) How feasible and acceptable are exercise interventions for tendinopathies? Methods: A scoping review mapped exercise interventions for tendinopathies and outcomes reported to date (questions i and ii). Thereafter, two contingent systematic review workstreams were conducted. The first investigated a large number of studies and was split into three efficacy reviews that quantified and compared efficacy across different interventions (question iii), and investigated the influence of a range of potential moderators (question iv). The second was a convergent segregated mixed-method review (question v). Searches for studies published from 1998 were conducted in library databases (n = 9), trial registries (n = 6), grey literature databases (n = 5) and Google Scholar. Scoping review searches were completed on 28 April 2020 with efficacy and mixed-method search updates conducted on 19 January 2021 and 29 March 2021. Results: Scoping review - 555 included studies identified a range of exercise interventions and outcomes across a range of tendinopathies, most commonly Achilles, patellar, lateral elbow and rotator cuff-related shoulder pain. Strengthening exercise was most common, with flexibility exercise used primarily in the upper limb. Disability was the most common outcome measured in Achilles, patellar and rotator cuff-related shoulder pain; physical function capacity was most common in lateral elbow tendinopathy. Efficacy reviews - 204 studies provided evidence that exercise therapy is safe and beneficial, and that patients are generally satisfied with treatment outcome and perceive the improvement to be substantial. In the context of generally low and very low-quality evidence, results identified that: (1) the shoulder may benefit more from flexibility (effect sizeResistance:Flexibility = 0.18 [95% CrI 0.07 to 0.29]) and proprioception (effect sizeResistance:Proprioception = 0.16 [95% CrI -1.8 to 0.32]); (2) when performing strengthening exercise it may be most beneficial to combine concentric and eccentric modes (effect sizeEccentricOnly:Concentric+Eccentric = 0.48 [95% CrI -0.13 to 1.1]; and (3) exercise may be most beneficial when combined with another conservative modality (e.g. injection or electro-therapy increasing effect size by ≈0.1 to 0.3). Mixed-method review - 94 studies (11 qualitative) provided evidence that exercise interventions for tendinopathy can largely be considered feasible and acceptable, and that several important factors should be considered when prescribing exercise for tendinopathy, including an awareness of potential barriers to and facilitators of engaging with exercise, patients' and providers' prior experience and beliefs, and the importance of patient education, self-management and the patient-healthcare professional relationship. Limitations: Despite a large body of literature on exercise for tendinopathy, there are methodological and reporting limitations that influenced the recommendations that could be made. Conclusion: The findings provide some support for the use of exercise combined with another conservative modality; flexibility and proprioception exercise for the shoulder; and a combination of eccentric and concentric strengthening exercise across tendinopathies. However, the findings must be interpreted within the context of the quality of the available evidence. Future work: There is an urgent need for high-quality efficacy, effectiveness, cost-effectiveness and qualitative research that is adequately reported, using common terminology, definitions and outcomes. Study registration: This project is registered as DOI: 10.11124/JBIES-20-00175 (scoping review); PROSPERO CRD 42020168187 (efficacy reviews); https://osf.io/preprints/sportrxiv/y7sk6/ (efficacy review 1); https://osf.io/preprints/sportrxiv/eyxgk/ (efficacy review 2); https://osf.io/preprints/sportrxiv/mx5pv/ (efficacy review 3); PROSPERO CRD42020164641 (mixed-method review). Funding: This project was funded by the National Institute for Health and Care Research (NIHR) HTA programme and will be published in full in HTA Journal; Vol. 27, No. 24. See the NIHR Journals Library website for further project information.

Tendons are cords of strong, flexible tissue that attach muscles to bones, allowing joints to move. Tendinopathy is a common condition that can affect any tendon in the body, causing pain and limiting function. Exercise is often used to treat tendinopathy. We examined over 500 research papers on exercise for tendinopathy. The most common tendons to be studied were the calf (Achilles), knee (patellar), elbow and shoulder. Strengthening exercise was studied most often, especially in lower-limb tendinopathy. Other types of exercise such as stretching, balance and aerobic activity were less common, but were used to some extent in the upper and lower limbs. We found that exercise therapy is safe and beneficial for the tendinopathies that have been studied to date. Exercise may be most beneficial when combined with another intervention such as injection or electro-therapy. Strengthening exercise may be most beneficial for lower-limb tendinopathies. However, more research is needed on the type of strengthening and the dosage, such as how many exercises and how much resistance to use. Shoulder tendinopathies may benefit from exercise that targets joint flexibility and position more than strengthening. We also found that people who receive exercise therapy for tendinopathy are generally satisfied with the effect it has on their symptoms. Finally, we found that an individualised, person-centred approach to delivering exercise therapy is valued by people with tendinopathy. They also believe that the patient-healthcare provider relationship is important for promoting the confidence and motivation people need to continue with exercise programmes, especially when they complete them independently. Although we examined a lot of papers, many of the studies were low quality. This means there is still a need for high-quality studies to tell us how effective specific types of exercise are for specific tendinopathies. There is also a need for more studies on patients' and professionals' experiences of receiving or providing exercise for tendinopathy.

Manual patient handling in the healthcare setting: a scoping review.

BACKGROUND: Manual patient handling is the most frequently reported risk factor for work related musculoskeletal disorders in healthcare. Patient handling tasks are routinely performed manually without assistive devices and can create awkward postures and high loads for nurses and allied health professionals (AHPs). However, AHPs, notably physiotherapists, also utilize therapeutic handling to facilitate patient movement during rehabilitation. OBJECTIVES: To comprehensively map the literature surrounding manual patient handling (without assistive devices) by healthcare practitioners. METHODS: AMED, CINAHL, MEDLINE, SPORTDiscus, and EMBASE databases were searched. Grey literature was sourced from Google Scholar, EThOS, Open Grey, Health and Safety Executive, National Institute for Occupational Safety and Health and Work Safe Australia. Literature published in English between 2002 and 2021 was included. RESULTS: Forty-nine records were included: 36 primary research studies, 1 systematic review and 12 'other' including narrative and government reports. Primary research was predominantly observational cross-sectional (n = 21). The most common settings included laboratories (n = 13) and hospitals (n = 13). Seven research questions were identified, with patient handling practices (n = 13) the most common. Nurses formed the largest practitioner population (n = 13) and patients were often simulated (n = 12). Common outcomes included tasks performed (n = 13) and physical demands during patient handling (n = 13). CONCLUSION AND IMPLICATIONS OF KEY FINDINGS: This comprehensive scoping review identified that most research was observational, investigating nurses in hospitals or laboratories. More research on manual patient handling by AHPs and investigation of the biomechanics involved in therapeutic handling is needed. Further qualitative research would allow for greater understanding of manual patient handling practices within healthcare. CONTRIBUTION OF THE PAPER.

Effect of resistance exercise dose components for tendinopathy management: a systematic review with meta-analysis.

OBJECTIVE: To investigate potential moderating effects of resistance exercise dose components including intensity, volume and frequency, for the management of common tendinopathies. DESIGN: Systematic review with meta-analysis and meta-regressions. DATA SOURCES: Including but not limited to: MEDLINE, CINAHL, SPORTDiscus, ClinicalTrials.gov and ISRCTN Registry. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised and non-randomised controlled trials investigating resistance exercise as the dominant treatment class, reporting sufficient information regarding ≥2 components of exercise dose. RESULTS: A total of 110 studies were included in meta-analyses (148 treatment arms (TAs), 3953 participants), reporting on five tendinopathy locations (rotator cuff: 48 TAs; Achilles: 43 TAs; lateral elbow: 29 TAs; patellar: 24 TAs; gluteal: 4 TAs). Meta-regressions provided consistent evidence of greater pooled mean effect sizes for higher intensity therapies comprising additional external resistance compared with body mass only (large effect size domains: ß BodyMass: External = 0.50 (95% credible interval (CrI): 0.15 to 0.84; p=0.998); small effect size domains (ß BodyMass: External = 0.04 (95% CrI: -0.21 to 0.31; p=0.619)) when combined across tendinopathy locations or analysed separately. Greater pooled mean effect sizes were also identified for the lowest frequency (less than daily) compared with mid (daily) and high frequencies (more than once per day) for both effect size domains when combined or analysed separately (p≥0.976). Evidence for associations between training volume and pooled mean effect sizes was minimal and inconsistent. SUMMARY/CONCLUSION: Resistance exercise dose is poorly reported within tendinopathy management literature. However, this large meta-analysis identified some consistent patterns indicating greater efficacy on average with therapies prescribing higher intensities (through inclusion of additional loads) and lower frequencies, potentially creating stronger stimuli and facilitating adequate recovery.

What are small, medium and large effect sizes for exercise treatments of tendinopathy? A systematic review and meta-analysis.

Objective: To quantify and describe effect size distributions from exercise therapies across a range of tendinopathies and outcome domains to inform future research and clinical practice through conducting a systematic review with meta-analysis. Design: Systematic review with meta-analysis exploring moderating effects and context-specific small, medium and large thresholds. Eligibility criteria: Randomised and quasi-randomised controlled trials involving any persons with a diagnosis of rotator cuff, lateral elbow, patellar, Achilles or gluteal tendinopathy of any severity or duration. Methods: Common databases, six trial registries and six grey literature databases were searched on 18 January 2021 (PROSPERO: CRD42020168187). Standardised mean difference (SMDpre) effect sizes were used with Bayesian hierarchical meta-analysis models to calculate the 0.25 (small), 0.5 (medium) and 0.75 quantiles (large) and compare pooled means across potential moderators. Risk of bias was assessed with Cochrane's Risk of Bias tool. Results: Data were obtained from 114 studies comprising 171 treatment arms 4104 participants. SMDpre effect sizes were similar across tendinopathies but varied across outcome domains. Greater threshold values were obtained for self-reported measures of pain (small=0.5, medium=0.9 and large=1.4), disability (small=0.6, medium=1.0 and large=1.5) and function (small=0.6, medium=1.1 and large=1.8) and lower threshold values obtained for quality of life (small=-0.2, medium=0.3 and large=0.7) and objective measures of physical function (small=0.2, medium=0.4 and large=0.7). Potential moderating effects of assessment duration, exercise supervision and symptom duration were also identified, with greater pooled mean effect sizes estimated for longer assessment durations, supervised therapies and studies comprising patients with shorter symptom durations. Conclusion: The effect size of exercise on tendinopathy is dependent on the type of outcome measure assessed. Threshold values presented here can be used to guide interpretation and assist with further research better establishing minimal important change.

Time Course of Neurobehavioral Disruptions and Regional Brain Metabolism Changes in the Rotenone Mice Model of Parkinson's Disease.

Parkinson's disease (PD) is characterized by slow progression with a long prodromal stage and the gradual evolution of both neuropsychological symptoms and subtle motor changes, preceding motor dysfunction. Thus, in order for animal models of PD to be valid, they should reproduce these characteristics of the disease. One of such models, in which neuropathology is induced by chronic injections of low doses of mitochondrial toxin rotenone, is well established in rats. However, data on this model adapted to mice remain controversial. We have designed the study to describe the timecourse of motor and non-motor symptoms during chronic subcutaneous administration of rotenone (4 mg/kg daily for 35 days) in C57BL/6 mice. We characterize the underlying neuropathological processes (dopaminergic neuron degeneration, regional brain metabolism, monoamine neurotransmitter and lipid peroxidation changes) at different timepoints: 1 day, 2 weeks and 5 weeks of daily rotenone exposure. Based on the behavioral data, we can describe three stages of pathology: cognitive changes from week 2 of rotenone exposure, subtle motor changes in week 3-4 and motor dysfunction starting roughly from week 4. Neuropathological changes in this model include a general decrease in COX activity in different areas of the brain (acute effect of rotenone) and a more specific decrease in midbrain (chronic effect), followed by significant neurodegeneration in SNpc but not VTA by the 5th week of rotenone exposure. However, we were unable to find changes in the level of monoamine neurotransmitters neither in the striatum nor in the cortex, nor in the level of lipid peroxidation in the brainstem. Thus, the gradual progression of pathology in this model is linked with metabolic changes, rather than with oxidative stress or tonic neurotransmitter release levels. Overall, this study supports the idea that a low-dose rotenone mouse model can also reproduce different stages of PD as well as rats.

Mobile Colistin Resistance Genetic Determinants of Non-Typhoid Salmonella enterica Isolates from Russia.

Polymyxin resistance, determined by mcr genes located on plasmid DNA, currently poses a high epidemiological threat. Non-typhoid Salmonella (NTS) are one of the key pathogens causing diarrheal diseases. Here, we report the isolation and whole genome sequencing of multidrug colistin-resistant/susceptible isolates of non-typhoid Salmonella enterica serovars carrying mcr genes. Non-typhoid strains of Salmonella enterica subsp. enterica were isolated during microbiological monitoring of the environment, food, and diarrheal disease patients between 2018 and 2020 in Russia (n = 586). mcr-1 genes were detected using a previously developed qPCR assay, and whole genome sequencing of mcr positive isolates was performed by both short-read (Illumina) and long-read (Oxford Nanopore) approaches. Three colistin-resistant isolates, including two isolates of S. Enteritidis and one isolate of S. Bovismorbificans, carried the mcr-1.1 gene located on IncX4 and IncI2 conjugative plasmids, respectively. The phenotypically colistin-susceptible isolate of S. Typhimurium carried a mcr-9 gene on plasmid IncHI2. In conclusion, we present the first three cases of mcr gene-carrying NTS isolates detected in Russia with both outbreak and sporadic epidemiological backgrounds.

Health technologies for the prevention and detection of falls in adult hospital inpatients: a scoping review.

OBJECTIVE: The objective of this scoping review was to examine and map the evidence relating to the reporting and evaluation of technologies for the prevention and detection of falls in adult hospital inpatients. INTRODUCTION: Falls are a common cause of accidental injury, leading to significant safety issues in hospitals globally, and resulting in substantial human and economic costs. Previous research has focused on community settings with less emphasis on hospital settings. INCLUSION CRITERIA: Participants included adult inpatients, aged 18 years and over; the concept included the use of fall-prevention or fall-detection technologies; the context included any hospital ward setting. METHODS: This scoping review was conducted according to JBI methodology for scoping reviews, guided by an a priori protocol. A wide selection of databases including MEDLINE, CINAHL, AMED, Embase, PEDro, Epistimonikos, and Science Direct were searched for records from inception to October 2019. Other sources included gray literature, trial registers, government health department websites, and websites of professional bodies. Only studies in the English language were included. A three-step search strategy was employed, with all records exported for subsequent title and abstract screening prior to full-text screening. Screening was performed by two independent reviewers and data extraction by one reviewer following agreement checks. Data are presented in narrative and tabular form. RESULTS: Over 13,000 records were identified with 404 included in the scoping review: 336 reported on fall-prevention technologies, 51 targeted detection, and 17 concerned both. The largest contributions of studies came from the USA (n=185), Australia (n=65), the UK (n=36), and Canada (n=18). There was a variety of study designs including 77 prospective cohort studies, 33 before-after studies, and 35 systematic reviews; however, relatively few randomized controlled trials were conducted (n = 25). The majority of records reported on multifactorial and multicomponent technologies (n = 178), followed by fall detection devices (n = 86). Few studies reported on the following interventions in isolation: fall risk assessment (n = 6), environment design (n = 8), sitters (n = 5), rounding (n = 3), exercise (n = 3), medical/pharmaceutical (n = 2), physiotherapy (n = 1), and nutritional (n = 1). The majority (57%) of studies reported clinical effectiveness outcomes, with smaller numbers (14%) reporting feasibility and/or acceptability outcomes, or cost-effectiveness outcomes (5%). CONCLUSIONS: This review has mapped the literature on fall-prevention and fall-detection technology and outcomes for adults in the hospital setting. Despite the volume of available literature, there remains a need for further high-quality research on fall-prevention and fall-detection technologies.

Water-soluble triazole chitin derivative and its based nanoparticles: Synthesis, characterization, catalytic and antibacterial properties.

In this work, we treated chitin with 2-(azidomethyl)oxirane and successfully involved the resultant azido chitin derivatives in the ultrasound-assisted Cu(I)-catalyzed azido-alkyne click (CuAAC) reaction with propargylic ester of N,N,N-trimethyl glycine. Thus, we obtained novel water-soluble triazole chitin derivatives. The triazole chitin derivatives and their nanoparticles are characterized by a high in vitro antibacterial activity, which is the same or even higher than that of commercial antibiotics ampicillin and gentamicin. The obtained derivatives are non-toxic. Moreover, the obtained water-soluble polymers are highly efficient green catalysts for the aldol reaction in green solvent water. The catalysts can be easily extracted from the reaction mixture by its precipitation with green solvent ethanol followed by centrifugation and they can be reused at least 10 times.

Is intrinsic lumbar spine shape associated with lumbar disc degeneration? An exploratory study.

BACKGROUND: Lumbar disc degeneration (LDD) is a condition associated with recurrent low back pain (LBP). Knowledge regarding effective management is limited. As a step towards the identification of risk, prognostic or potentially modifiable factors in LDD patients, the aim of this study was to explore the hypothesis that intrinsic lumbar spine shape is associated with LDD and clinical outcomes in symptomatic adults. METHODS: 3 T MRI was used to acquire T2-weighted sagittal images (L1-S1) from 70 healthy controls and LDD patients (mean age 49 years, SD 11, range 31-71 years). Statistical Shape Modelling (SSM) was used to describe lumbar spine shape. SSM identified variations in lumbar shape as 'modes' of variation and quantified deviation from the mean. Intrinsic shape differences were determined between LDD groups using analysis of variance with post-hoc comparisons. The relationship between intrinsic shape and self-reported function, mental health and quality of life were also examined. RESULTS: The first 7 modes of variation explained 91% of variance in lumbar shape. Higher LDD sum scores correlated with a larger lumbar lordosis (Mode 1 (55% variance), P = 0.02), even lumbar curve distribution (Mode 2 (12% variance), P = 0.05), larger anterior-posterior (A-P) vertebral diameter (Mode 3 (10% variance), P = 0.007) and smaller L4-S1 disc spaces (Mode 7 (2% variance), P ≤ 0.001). In the presence of recurrent LBP, LDD was associated with a larger A-P vertebral diameter (Mode 3) and a more even lumbar curvature with smaller L5/S1 disc spaces (Mode 4), which was significantly associated with patient quality of life (P = 0.002-0.04, rp = 0.43-0.61)). CONCLUSIONS: This exploratory study provides new evidence that intrinsic shape phenotypes are associated with LDD and quality of life in patients. Longitudinal studies are required to establish the potential role of these risk or prognostic shape phenotypes.

Motor development in infancy and spine shape in early old age: Findings from a British birth cohort study.

Spine shape changes dramatically in early life, influenced by attainment of developmental milestones such as independent walking. Whether these associations persist across life is unknown. Therefore, we investigated associations between developmental milestones and spine shape, as determined using statistical shape models (SSMs) of lumbar spine from dual-energy X-ray absorptiometry scans in 1327 individuals (688 female) at 60 to 64 years in the MRC National Survey of Health and Development. Lumbar lordosis angle (L4 inferior endplate to T12 superior endplate) was measured using the two-line Cobb method. In analyses adjusted for sex, height, lean and fat mass, socioeconomic position, and birthweight, later walking age was associated with greater lordosis described by SSM1 (regression coefficient, 0.023; 95% CI, 0.000-0.047; P = .05) and direct angle measurement. Modest associations between walking age and less variation in anterior-posterior vertebral size caudally (SSM6) were also observed (0.021; 95% CI, -0.002 to 0.044; P = .07). Sex interactions showed that later walking was associated with larger relative vertebral anterior-posterior dimensions in men (SSM3; -0.043; 95% CI, -0.075 to 0.01; P = .01) but not women (0.018; 95% CI, -0.0007 to 0.043; P = .17). Similar associations were observed between age at independent standing and SSMs but there was little evidence of association between sitting age and spine shape. Unadjusted associations between walking age and SSMs 1 and 6 remained similar after adjustment for potential confounders and mediators. This suggests that these associations may be explained by altered mechanical loading of the spine during childhood growth, although other factors could contribute. Early life motor development, particularly walking, may have a lasting effect on the features of spine morphology with clinical significance.

Perinatal factors associate with vertebral size and shape but not lumbar lordosis in 10-year-old children.

The intrauterine environment is known to influence foetal development and future health. Low birthweight has been linked to smaller vertebral canals in children and decreased adulthood spine bone mineral content. Perinatal factors affecting lumbar spine curvature have not yet been considered but could be important for adult spinal health, as lumbar movement during lifting, a risk factor for backpain, is associated with lordosis. To investigate this, lumbar spine magnetic resonance images at age 10 years and perinatal and maternal data (birthweight, placental weight, gestation length, crown-heel length, maternal age, height, weight and smoking status) from 161 children born in Aberdeen in 1988-1989 were acquired. Statistical shape modelling, using principal component analysis, quantified variations in lumbar spine shape and resulting modes of variation were assessed in combination with perinatal data using correlations and analyses of covariance, adjusted for potential confounders. Spine modes 1-3 (SM1-SM3) captured 75% of the variation in lumbar spine shape. The first and third modes described the total amount (SM1) and evenness of curvature distribution (SM3). SM2 accounted for variations in antero-posterior vertebral diameter relative to vertebral height, increasing positive scores representing a larger relative diameter. Adjusting for gestation length and sex, SM2 positively correlated with birthweight (r = 0.25, P < 0.01), placental weight (r = 0.20, P = 0.04), crown-heel length (r = 0.36, P < 0.001) and maternal weight (r = 0.19, P = 0.04), and negatively with maternal age (r = -0.22, P = 0.02). SM2 scores were lower in girls (P < 0.001) and in the low birthweight group (P = 0.02). There were no significant differences in SM1 and SM3 scores between birthweight groups, boys and girls or children of smokers (31%) and non-smokers (69%). In conclusion, some perinatal factors were associated with vertebral body morphology but had little effect on lumbar curvature.

Age at Onset of Walking in Infancy Is Associated With Hip Shape in Early Old Age.

Bones' shapes and structures adapt to the muscle and reaction forces they experience during everyday movements. Onset of independent walking, at approximately 12 months, represents the first postnatal exposure of the lower limbs to the large forces associated with bipedal movements; accordingly, earlier walking is associated with greater bone strength. However, associations between early life loading and joint shape have not been explored. We therefore examined associations between walking age and hip shape at age 60 to 64 years in 1423 individuals (740 women) from the MRC National Survey of Health and Development, a nationally representative British birth cohort. Walking age in months was obtained from maternal interview at age 2 years. Ten modes of variation in hip shape (HM1 to HM10), described by statistical shape models, were ascertained from DXA images. In sex-adjusted analyses, earlier walking age was associated with higher HM1 and HM7 scores; these associations were maintained after further adjustment for height, body composition, and socioeconomic position. Earlier walking was also associated with lower HM2 scores in women only, and lower HM4 scores in men only. Taken together, this suggests that earlier walkers have proportionately larger (HM4) and flatter (HM1, HM4) femoral heads, wider (HM1, HM4, HM7) and flatter (HM1, HM7) femoral necks, a smaller neck-shaft angle (HM1, HM4), anteversion (HM2, HM7), and early development of osteophytes (HM1). These results suggest that age at onset of walking in infancy is associated with variations in hip shape in older age. Early walkers have a larger femoral head and neck and smaller neck-shaft angle; these features are associated with reduced hip fracture risk, but also represent an osteoarthritic-like phenotype. Unlike results of previous studies of walking age and bone mass, associations in this study were not affected by adjustment for lean mass, suggesting that associations may relate directly to skeletal loading in early life when joint shape changes rapidly. © 2018 American Society for Bone and Mineral Research.

Associations between back pain across adulthood and spine shape in early old age in a British birth cohort.

We aimed to examine whether back pain across adulthood was associated with spine shape at age 60-64 years. Data were from 1405 participants in the MRC National Survey of Health and Development, a nationally representative British birth cohort. Back pain was ascertained during nurse interviews at ages 36, 43, 53 and 60-64 years. Cumulative exposure to back pain was then derived by counting the number of ages at which back pain was reported. Statistical shape modelling was used to characterise thoracolumbar spine shape using lateral dual-energy x-ray absorptiometry images which were ascertained at age 60-64 years. Linear regression models were used to test associations of spine shape modes (SM) with: (1) cumulative exposure to back pain; (2) back pain reports during different periods of adulthood. After adjusting for sex, higher cumulative exposure to back pain across adulthood was associated with wedge-shaped L4-5 disc (lower SM4 scores) and smaller disc spaces (higher SM8 scores) in both sexes. In addition, reporting of back pain at ages 53 and/or 60-64 years was associated with smaller L4-5 disc space (lower SM6 scores) in men but not women. These findings suggest that back pain across adulthood may be associated with specific variations in spine shapes in early old age.

Variation in lifting kinematics related to individual intrinsic lumbar curvature: an investigation in healthy adults.

OBJECTIVE: Lifting postures are frequently implicated in back pain. We previously related responses to a static load with intrinsic spine shape, and here we investigate the role of lumbar spine shape in lifting kinematics. METHODS: Thirty healthy adults (18-65 years) performed freestyle, stoop and squat lifts with a weighted box (6-15 kg, self-selected) while being recorded by Vicon motion capture. Internal spine shape was characterised using statistical shape modelling (SSM) from standing mid-sagittal MRIs. Associations were investigated between spine shapes quantified by SSM and peak flexion angles. RESULTS: Two SSM modes described variations in overall lumbar curvature (mode 1 (M1), 55% variance) and the evenness of curvature distribution (mode 2 (M2), 12% variance). M1 was associated with greater peak pelvis (r=0.38, p=0.04) and smaller knee flexion (r=-0.40, p=0.03) angles; individuals with greater curviness preferred to lift with a stooped lifting posture. This was confirmed by analysis of those individuals with very curvy or very straight spines (|M1|>1 SD). There were no associations between peak flexion angles and mode scores in stoop or squat trials (p>0.05). Peak flexion angles were positively correlated between freestyle and squat trials but not between freestyle and stoop or squat and stoop, indicating that individuals adjusted knee flexion while maintaining their preferred range of lumbar flexion and that 'squatters' adapted better to different techniques than 'stoopers'. CONCLUSION: Spinal curvature affects preferred lifting styles, and individuals with curvier spines adapt more easily to different lifting techniques. Lifting tasks may need to be tailored to an individual's lumbar spine shape.

Body mass index and waist circumference in early adulthood are associated with thoracolumbar spine shape at age 60-64: The Medical Research Council National Survey of Health and Development.

This study investigated associations between measures of adiposity from age 36 and spine shape at 60-64 years. Thoracolumbar spine shape was characterised using statistical shape modelling on lateral dual-energy x-ray absorptiometry images of the spine from 1529 participants of the MRC National Survey of Health and Development, acquired at age 60-64. Associations of spine shape modes with: 1) contemporaneous measures of total and central adiposity (body mass index (BMI), waist circumference (WC)) and body composition (android:gynoid fat mass ratio and lean and fat mass indices, calculated as whole body (excluding the head) lean or fat mass (kg) divided by height2 (m)2); 2) changes in total and central adiposity between age 36 and 60-64 and 3) age at onset of overweight, were tested using linear regression models. Four modes described 79% of the total variance in spine shape. In men, greater lean mass index was associated with a larger lordosis whereas greater fat mass index was associated with straighter spines. Greater current BMI was associated with a more uneven curvature in men and with larger anterior-posterior (a-p) vertebral diameters in both sexes. Greater WC and fat mass index were also associated with a-p diameter in both sexes. There was no clear evidence that gains in BMI and WC during earlier stages of adulthood were associated with spine shape but younger onset of overweight was associated with a more uneven spine and greater a-p diameter. In conclusion, sagittal spine shapes had different associations with total and central adiposity; earlier onset of overweight and prior measures of WC were particularly important.

Associations between body mass index across adult life and hip shapes at age 60 to 64: Evidence from the 1946 British birth cohort.

OBJECTIVE: To examine the associations of body mass index (BMI) across adulthood with hip shapes at age 60-64years. METHODS: Up to 1633 men and women from the MRC National Survey of Health and Development with repeat measures of BMI across adulthood and posterior-anterior dual-energy X-ray absorptiometry bone mineral density images of the proximal femur recorded at age 60-64 were included in analyses. Statistical shape modelling was applied to quantify independent variations in hip mode (HM), of which the first 6 were examined in relation to: i) BMI at each age of assessment; ii) BMI gain during different phases of adulthood; iii) age first overweight. RESULTS: Higher BMI at all ages (i.e. 15 to 60-64) and greater gains in BMI were associated with higher HM2 scores in both sexes (with positive HM2 values representing a shorter femoral neck and a wider and flatter femoral head). Similarly, younger age first overweight was associated with higher HM2 scores but only in men once current BMI was accounted for. In men, higher BMI at all ages was also associated with lower HM4 scores (with negative HM4 values representing a flatter femoral head, a wider neck and smaller neck shaft angle) but no associations with BMI gain or prolonged exposure to high BMI were found. Less consistent evidence of associations was found between BMI and the other four HMs. CONCLUSION: These results suggest that BMI across adulthood may be associated with specific variations in hip shapes in early old age.

Statistical shape modelling of hip and lumbar spine morphology and their relationship in the MRC National Survey of Health and Development.

The anatomical shape of bones and joints is important for their proper function but quantifying this, and detecting pathological variations, is difficult to do. Numerical descriptions would also enable correlations between joint shapes to be explored. Statistical shape modelling (SSM) is a method of image analysis employing pattern recognition statistics to describe and quantify such shapes from images; it uses principal components analysis to generate modes of variation describing each image in terms of a set of numerical scores after removing global size variation. We used SSM to quantify the shapes of the hip and the lumbar spine in dual-energy x-ray absorptiometry (DXA) images from 1511 individuals in the MRC National Survey of Health and Development at ages 60-64 years. We compared shapes of both joints in men and women and hypothesised that hip and spine shape would be strongly correlated. We also investigated associations with height, weight, body mass index (BMI) and local (hip or lumber spine) bone mineral density. In the hip, all except one of the first 10 modes differed between men and women. Men had a wider femoral neck, smaller neck-shaft angle, increased presence of osteophytes and a loss of the femoral head/neck curvature compared with women. Women presented with a flattening of the femoral head and greater acetabular coverage of the femoral head. Greater weight was associated with a shorter, wider femoral neck and larger greater and lesser trochanters. Taller height was accompanied by a flattening of the curve between superior head and neck and a larger lesser trochanter. Four of the first eight modes describing lumbar spine shape differed between men and women. Women tended to have a more lordotic spine than men with relatively smaller but caudally increasing anterior-posterior (a-p) vertebral diameters. Men were more likely to have a straighter spine with larger vertebral a-p diameters relative to vertebral height than women, increasing cranially. A weak correlation was found between body weight and a-p vertebral diameter. No correlations were found between shape modes and height in men, whereas in women there was a weak positive correlation between height and evenness of spinal curvature. Linear relationships between hip and spine shapes were weak and inconsistent in both sexes, thereby offering little support for our hypothesis. In conclusion, men and women entering their seventh decade have small but statistically significant differences in the shapes of their hips and their spines. Associations with height, weight, BMI and BMD are small and correspond to subtle variations whose anatomical significance is not yet clear. Correlations between hip and spine shapes are small.