Decoding human fetal liver haematopoiesis.

Definitive haematopoiesis in the fetal liver supports self-renewal and differentiation of haematopoietic stem cells and multipotent progenitors (HSC/MPPs) but remains poorly defined in humans. Here, using single-cell transcriptome profiling of approximately 140,000 liver and 74,000 skin, kidney and yolk sac cells, we identify the repertoire of human blood and immune cells during development. We infer differentiation trajectories from HSC/MPPs and evaluate the influence of the tissue microenvironment on blood and immune cell development. We reveal physiological erythropoiesis in fetal skin and the presence of mast cells, natural killer and innate lymphoid cell precursors in the yolk sac. We demonstrate a shift in the haemopoietic composition of fetal liver during gestation away from being predominantly erythroid, accompanied by a parallel change in differentiation potential of HSC/MPPs, which we functionally validate. Our integrated map of fetal liver haematopoiesis provides a blueprint for the study of paediatric blood and immune disorders, and a reference for harnessing the therapeutic potential of HSC/MPPs.

Gene expression variability across cells and species shapes innate immunity.

As the first line of defence against pathogens, cells mount an innate immune response, which varies widely from cell to cell. The response must be potent but carefully controlled to avoid self-damage. How these constraints have shaped the evolution of innate immunity remains poorly understood. Here we characterize the innate immune response's transcriptional divergence between species and variability in expression among cells. Using bulk and single-cell transcriptomics in fibroblasts and mononuclear phagocytes from different species, challenged with immune stimuli, we map the architecture of the innate immune response. Transcriptionally diverging genes, including those that encode cytokines and chemokines, vary across cells and have distinct promoter structures. Conversely, genes that are involved in the regulation of this response, such as those that encode transcription factors and kinases, are conserved between species and display low cell-to-cell variability in expression. We suggest that this expression pattern, which is observed across species and conditions, has evolved as a mechanism for fine-tuned regulation to achieve an effective but balanced response.

Transport digitalisation: Navigating futures of hypercognitive disablement.

People living with cognitive impairments face new forms of disablement in the context of transport digitalisation, an issue recently catalysed by controversies regarding rail ticket office closures. Transport can dramatically impact the lives of people diagnosed with dementia, who often find their mobility suddenly and dramatically impaired. Unfortunately, sociological analysis of cognitive disability has traditionally been undermined by under-theorisation. One solution can be found in classic bioethical work on hypercognitivism-the veneration of cognitive acuity-and its disabling consequences. A hypercognitive approach can nurture an attentiveness to the specificities of digital disablement. Here, disability does not emerge from digitalisation inherently, but is instead intensified by the implementation of digitalisation in line with value commitments. A more robust sociology of cognitive disability could better represent the interests of people with cognitive impairments and resist the new forms of disability that current digitalisation risks spreading.

How frail is frail in oncology studies? A scoping review.

AIMS: The frailty index (FI) is one way in which frailty can be quantified. While it is measured as a continuous variable, various cut-off points have been used to categorise older adults as frail or non-frail, and these have largely been validated in the acute care or community settings for older adults without cancer. This review aimed to explore which FI categories have been applied to older adults with cancer and to determine why these categories were selected by study authors. METHODS: This scoping review searched Medline, EMBASE, Cochrane, CINAHL, and Web of Science databases for studies which measured and categorised an FI in adults with cancer. Of the 1994 screened, 41 were eligible for inclusion. Data including oncological setting, FI categories, and the references or rationale for categorisation were extracted and analysed. RESULTS: The FI score used to categorise participants as frail ranged from 0.06 to 0.35, with 0.35 being the most frequently used, followed by 0.25 and 0.20. The rationale for FI categories was provided in most studies but was not always relevant. Three of the included studies using an FI > 0.35 to define frailty were frequently referenced as the rationale for subsequent studies, however, the original rationale for this categorisation was unclear. Few studies sought to determine or validate optimum FI categorises in this population. CONCLUSION: There is significant variability in how studies have categorised the FI in older adults with cancer. An FI ≥ 0.35 to categorise frailty was used most frequently, however an FI in this range has often represented at least moderate to severe frailty in other highly-cited studies. These findings contrast with a scoping review of highly-cited studies categorising FI in older adults without cancer, where an FI ≥ 0.25 was most common. Maintaining the FI as a continuous variable is likely to be beneficial until further validation studies determine optimum FI categories in this population. Differences in how the FI has been categorised, and indeed how older adults have been labelled as 'frail', limits our ability to synthesise results and to understand the impact of frailty in cancer care.

Administration of immune checkpoint inhibitors at rural towns using the Teleoncology model of care-A North Queensland perspective.

OBJECTIVE: This study aimed at evaluating the safety of administering immune checkpoint inhibitors (ICIs) and monitoring for immune-related adverse events (irAEs) using the Teleoncology model of care. DESIGN: A retrospective cohort study comparing two patient groups. SETTING: The North Queensland Teleoncology Network (NQTN) operated by the Townsville (THHS) and Cairns Hospital Health Services (CHHS) with the Townsville Cancer Centre (TCC) acting as the control group setting. PARTICIPANTS: Patients who received ICI treatment via the NQTN between January 2015 and April 2019. Patients who received ICI at the TCC over the same time period were used for comparison. MAIN OUTCOME MEASURES: Rates of high-grade irAEs and irAE-related deaths. RESULTS: Fifty-two patients received a total of 822 cycles of ICIs via the Teleoncology model through NQTN. Over the same time period, 142 patients received a total of 1521 cycles at the TCC. There were no significant differences in all demographic characteristics between either group, including tumour profile and Indigenous status. There were no statistically significant differences between the rates of high-grade irAE across multiple body organ systems (p = 0.151) and rate of hospital admissions (13.5% (NQTN) vs 5.6% (TCC), p = 0.702). There were no irAE-related deaths in either group. CONCLUSIONS: The results suggest that with adequate governance and clinical resources, ICIs can be administered safely using Teleoncology models to rural and remote towns.

Synthetic Control of Exciton Dynamics in Bioinspired Cofacial Porphyrin Dimers.

Understanding how the complex interplay among excitonic interactions, vibronic couplings, and reorganization energy determines coherence-enabled transport mechanisms is a grand challenge with both foundational implications and potential payoffs for energy science. We use a combined experimental and theoretical approach to show how a modest change in structure may be used to modify the exciton delocalization, tune electronic and vibrational coherences, and alter the mechanism of exciton transfer in covalently linked cofacial Zn-porphyrin dimers (meso-beta linked ABm-ß and meso-meso linked AAm-m). While both ABm-ß and AAm-m feature zinc porphyrins linked by a 1,2-phenylene bridge, differences in the interporphyrin connectivity set the lateral shift between macrocycles, reducing electronic coupling in ABm-ß and resulting in a localized exciton. Pump-probe experiments show that the exciton dynamics is faster by almost an order of magnitude in the strongly coupled AAm-m dimer, and two-dimensional electronic spectroscopy (2DES) identifies a vibronic coherence that is absent in ABm-ß. Theoretical studies indicate how the interchromophore interactions in these structures, and their system-bath couplings, influence excitonic delocalization and vibronic coherence-enabled rapid exciton transport dynamics. Real-time path integral calculations reproduce the exciton transfer kinetics observed experimentally and find that the linking-modulated exciton delocalization strongly enhances the contribution of vibronic coherences to the exciton transfer mechanism, and that this coherence accelerates the exciton transfer dynamics. These benchmark molecular design, 2DES, and theoretical studies provide a foundation for directed explorations of nonclassical effects on exciton dynamics in multiporphyrin assemblies.

Merging antimicrobial and visible emission properties within 1,3,4-trisubstituted-1,2,3-triazolium salts.

Bioactive molecules displaying visible wavelength emission can be useful for bioimaging, chemosensing and photodynamic therapy applications. Reported herein are 1,3,4-trisubsituted-1,2,3-triazolium salts displaying both antimicrobial and visible emission properties. Using a click chemistry approach, 2-fluorenyl, 1-naphthyl, 2-naphthyl, 2-anthracenyl and 1-pyrenyl units were incorporated at the N1 position, imparting visible emission properties to their triazolium bromide salts with Stokes shifts greater than 100 nm relative to the emission of their triazole precursors. The increasing size of such hydrophobic aryl units impacts minimum inhibitory concentration (MIC) values against Gram-positive bacteria, Gram-negative bacteria and yeast, and can be counterbalanced by hydrophobic substituent variation at other positions of the molecule in order to preserve bioactivity. Among the series of compounds studied are analogs displaying blue, green and yellow colored emission and MIC values as low as 0.4 µM (Gram-positive bacteria), 8 µM (Gram-negative bacteria) and 2 µM (yeast). XRD analysis validates the regioselective benzylation at the N3 position of the 1,2,3-triazole ring and the ability of such compounds to associate through dimeric intermolecular π-stacking interactions.

Time-resolved observations of vibrationally excited NO X 2Π (v') formed from collisional quenching of NO A 2Σ+ (v = 0) by NO X 2Π: evidence for the participation of the NO a 4Π state.

Time-resolved observations have been made of the formation of vibrationally excited NO X 2Π (v') following collisional quenching of NO A 2Σ+ (v = 0) by NO X 2Π (v = 0). Two time scales are observed, namely a fast production rate consistent with direct formation from the quenching of the electronically excited NO A state, together with a slow component, the magnitude and rate of formation of which depend upon NO pressure. A reservoir state formed by quenching of NO A 2Σ+ (v = 0) is invoked to explain the observations, and the available evidence points to this state being the first electronically excited state of NO, a 4Π. The rate constant for quenching of the a 4Π state to levels v' = 11-16 by NO is measured as (8.80 ± 1.1) × 10-11 cm3 molecule-1 s-1 at 298 K where the error quoted is two standard deviations, and from measurements of the increased formation of high vibrational levels of NO(X) by the slow process we estimate a lower limit for the fraction of self-quenching collisions of NO A 2Σ+ (v = 0) which lead to NO a 4Π as 19%.

Structuring unequal relations: role trajectories in informal dementia care.

Transitions into informal care roles are associated with various characteristics, for example gender and geographic proximity, but such associations are insufficient to explain role delegation, overlooking the interpersonal structure-agency nexuses that constitute role trajectories. This paper explores unequal role delegation within 7 families affected by dementia, presenting data from interviews with 7 people with dementia and 26 carers living in the community in the United Kingdom. Two key care roles are identified: the relatively un-involved role of peripheral actors and the lynchpin role of main carers who take on most of the care tasks. These roles emerge from negotiations around a range of extraneous factors that collectively comprise cumulative baggage, including historic conflicts and childcare commitments. The unequal distribution of care reflects widely noted demographic associations with role delegation, but is enacted and justified through the interpersonal negotiation of personalised meanings regarding individual circumstances and suitability. Though deeply personal when taken at face value, these meanings imbibe sociocultural norms and political economies of care to structurally position family members in relation to each other and signpost appropriate candidates for caring roles, even before such care is required.

Age-associations in British politics: Implications for the sociology of aging.

Debates regarding the status of age in social analysis are foundational to the sociology of aging, with scholars continually questioning the role of age as a social force. The contemporary politicization of age in British politics sheds useful light on this debate. During the past decade, age has emerged as a potent predictor of political preference in the United Kingdom, encompassing numerous intertwined political economic developments. At face value, the emergence of age as a key political variable substantiates the status of age in social analysis. However, I argue that it is articulations of age-stratified politics, as much as the associations themselves, that should be of principle concern for the sociology of aging, because such articulations are reformulating age, aging and intergenerational relations. The sociology of aging should, therefore, engage with the contemporary politicization of age as a new answer to foundational debates.

Intracapsular Femoral Neck Fractures-A Surgical Management Algorithm.

Background and Objectives: Femoral neck fractures are common and constitute one of the largest healthcare burdens of the modern age. Fractures within the joint capsule (intracapsular) provide a specific surgical challenge due to the difficulty in predicting rates of bony union and whether the blood supply to the femoral head has been disrupted in a way that would lead to avascular necrosis. Most femoral neck fractures are treated surgically, aiming to maintain mobility, whilst reducing pain and complications associated with prolonged bedrest. Materials and Methods: We performed a narrative review of intracapsular hip fracture management, highlighting the latest advancements in fixation techniques, generating an evidence-based algorithm for their management. Results: Multiple different fracture configurations are encountered within the category of intracapsular hip fractures, with each pattern having different optimal surgical strategies. Additionally, these injuries typically occur in patients where further procedures due to operative complications are associated with a considerable increase in mortality, highlighting the need for choosing the correct index operation. Conclusions: Factors such as pathological causes for the fracture, pre-existing symptomatic osteoarthritis, patient's physiological age and fracture displacement all need to be considered when choosing optimal management.

Infrequent HIV Infection of Circulating Monocytes during Antiretroviral Therapy.

Whereas human immunodeficiency virus (HIV) persists in tissue macrophages during antiretroviral therapy (ART), the role of circulating monocytes as HIV reservoirs remains controversial. Three magnetic bead selection methods and flow cytometry cell sorting were compared for their capacity to yield pure CD14+ monocyte populations. Cell sorting by flow cytometry provided the purest population of monocytes (median CD4+ T-cell contamination, 0.06%), and the levels of CD4+ T-cell contamination were positively correlated with the levels of integrated HIV DNA in the monocyte populations. Using cell sorting by flow cytometry, we assessed longitudinally the infection of monocytes and other cell subsets in a cohort of 29 Thai HIV-infected individuals. Low levels of HIV DNA were detected in a minority of monocyte fractions obtained before and after 1 year of ART (27% and 33%, respectively), whereas HIV DNA was readily detected in CD4+ T cells from all samples. Additional samples (2 to 5 years of ART) were obtained from 5 individuals in whom monocyte infection was previously detected. Whereas CD4+ T cells were infected at high levels at all time points, monocyte infection was inconsistent and absent in at least one longitudinal sample from 4/5 individuals. Our results indicate that infection of monocytes is infrequent and highlight the importance of using flow cytometry cell sorting to minimize contamination by CD4+ T cells.IMPORTANCE The role of circulating monocytes as persistent HIV reservoirs during ART is still controversial. Several studies have reported persistent infection of monocytes in virally suppressed individuals; however, others failed to detect HIV in this subset. These discrepancies are likely explained by the diversity of the methods used to isolate monocytes and to detect HIV infection. In this study, we show that only flow cytometry cell sorting yields a highly pure population of monocytes largely devoid of CD4 contaminants. Using this approach in a longitudinal cohort of HIV-infected individuals before and during ART, we demonstrate that HIV is rarely found in monocytes from untreated and treated HIV-infected individuals. This study highlights the importance of using methods that yield highly pure populations of cells as flow cytometry cell sorting to minimize and control for CD4+ T-cell contamination.

Prostate Specific Membrane Antigen Targeted Positron Emission Tomography of Primary Prostate Cancer: Assessing Accuracy with Whole Mount Pathology.

PURPOSE: We evaluated which lesions are detected and missed on [68Ga]Ga-PSMA (prostate specific membrane antigen)-11 positron emission tomography in patients with primary prostate cancer. MATERIALS AND METHODS: Patients undergoing radical prostatectomy were enrolled in this prospective observational study. Patients underwent [68Ga]Ga-PSMA-11 positron emission tomography/computerized tomography or positron emission tomography/magnetic resonance imaging prior to surgery and received a dose of [68Ga]Ga-PSMA-11 intraoperatively for positron emission tomography of extirpated specimens. Whole mount pathology was performed with lesion and intralesion based analysis to determine the characteristics of lesions detected or not detected by PSMA positron emission tomography. Lesion volume was determined by planimetry and clinically significant lesion volume was calculated as lesion volume × fraction pattern 4/5. RESULTS: On whole mount analysis 30 cancerous lesions were found in a total of 15 patients, including 4, 15, 4, 1 and 6 which were Grade Group 1, 2, 3, 4 and 5, respectively. PSMA-positron emission tomography detected 100% of primary/index lesions and 8 of 11 (82%) secondary lesions. All Grade Group 3-5 lesions were detected vs 12 of 15 Grade Group 2 lesions. When comparing Grade Group 2 vs 3-5, lesion size was similar (p=0.48) but the standardized uptake value was lower for Grade Group 2 vs 3-5 (5.3 vs 7.9, p=0.03). The 3 missed lesions showed 10% or less of pattern 4 and a Gleason pattern 4/5 volume of less than 0.1 cm3. CONCLUSIONS: PSMA positron emission tomography detected 100% of primary/index lesions in this study. The 3 missed secondary lesions were small and had a low percent of pattern 4. This argues for further study to better understand what defines clinically significant prostate cancer, which would assist in determining whether small lesions that become challenging to detect by [68Ga]Ga-PSMA-11 positron emission tomography confer a risk to the patient.

Positioning ethnicity in dementia awareness research: does the use of senility risk ascribing racialised knowledge deficits to minority groups?

Over recent decades, the importance of increasing dementia awareness has been promoted by charities, researchers and governments. In response, a large body of research has emerged that evaluates the awareness of different populations. One such population are minority ethnic communities. Associated studies typically conclude that minority ethnic groups have a poor awareness of dementia and that interventions should be developed to better educate them. Operationalisations of awareness almost always reference senility - the traditional notion that dementia is a natural outcome of ageing - a widely held belief among many populations. Senility is considered incorrect knowledge in the research literature, and those participants who identify with it are deemed to have poor awareness. Despite the researchers' claims that senility is false, the scientific evidence is inconclusive, and the concept is contested. As such, a large body of research repeatedly positions minority ethnic communities as inferior and in need of re-education based on researchers' questionable assumptions. This issue is bound up with a racialised deficit-model of science communication and wider critiques of psychiatric colonialism. In response, researchers of dementia and ethnicity should reflect on their own awareness and the ways in which they position others in relation to it.

Ru(II) coordination compounds of N-N bidentate chelators with 1,2,3 triazole and isoquinoline subunits: Synthesis, spectroscopy and antimicrobial properties.

Bidentate chelators 1-(1-benzyl-1,2,3-triazol-4-yl)isoquinoline and 3-(1-benzyl-1,2,3-triazol-4-yl)isoquinoline were prepared from benzyl bromide and trimethylsilylethynylisoquinoline precursors using a tandem deprotection/substitution/CuAAC synthetic approach. Each chelator is capable of forming a stable 3:1 Ru(II) coordination compound, which forms as a geometric isomer mixture. These Ru(II) complexes possess unique MLCT absorbance signatures at 450/472 nm (1-isomer) and 367 nm (3-isomer) relative to their constituent chelating units. Minimum inhibitory concentration values as low as 0.4 µM are observed for Ru(II) complexes against representative Gram-positive bacteria Bacillus subtilis and Staphylococcus epidermidis. Comparing the MIC values of these isoquinoline compounds with analogous 2-(1-benzyl-1,2,3-triazol-4-yl)pyridine compounds shows a 2.5- to 40-fold improvement in potency. This study establishes that increased hydrophobicity introduced at the central chelating units of Ru(II) coordination compounds can be a useful means by which to optimize antimicrobial activity that is complimentary to the variation of peripheral substituent identity at the chelator's N1 triazole position.

Comparison of Two Handheld Digital Dual Inclinometry Techniques in the Measurement of Lumbar Flexion Active Range of Motion.

CONTEXT: An accurate assessment of lumbar spine active range of motion (AROM) is clinically important. Dual inclinometry is recommended as the optimal technique for measuring lumbar flexion AROM; however, the procedures differ in the literature. OBJECTIVE: To compare 2 different handheld digital dual inclinometry (HDDI) techniques for evaluating lumbar flexion AROM. DESIGN: The study was a repeated-measures design consisting of 2 trials. SETTING: Laboratory. PARTICIPANTS: A sample of 69 adult volunteers (28 men and 41 women; mean age 23.8 [2.4] y) without pain or injury to their back, hips, or abdomen for at least 3 months participated in the study. INTERVENTION: Using standardized methods, 1 trained tester performed 2 different HDDI measurements of standing lumbar flexion AROM on each subject. Each subject performed one repetition of AROM lumbar flexion per HDDI measurement. The HDDI measures differed in the process for placing the upper inclinometer, with one technique identifying the upper landmark by skilled palpation of the T12 spinous process and the other technique by measuring 15-cm cephalad to the S2 region landmark to approximate the location of the T12 spinous process. MAIN OUTCOME MEASURES: A dependent t test, Pearson correlation coefficient (r), the 95% limits of agreement, and Bland-Altman plots were used to examine agreement between the techniques. RESULTS: Dependent t testing showed no significant differences between the techniques (mean difference = 1.2°, P = .11). A strong correlation existed between the 2 HDDI techniques (r = .80, P < .001). The Bland-Altman plot illustrated that 64 of the 69 data points were within the 95% limits of agreement for the 2 techniques. CONCLUSIONS: The findings suggest that HDDI measurements of lumbar flexion AROM are comparable when using either of the 2 HDDI techniques described. Clinicians can make an evidence-based choice for using either method of measuring lumbar flexion AROM.

Very Early Initiation of Antiretroviral Therapy During Acute HIV Infection Is Associated With Normalized Levels of Immune Activation Markers in Cerebrospinal Fluid but Not in Plasma.

BACKGROUND: Chronic immune activation in the blood and central nervous system is a consequence of human immunodeficiency virus (HIV) infection that contributes to disease morbidity and can occur despite virally suppressive antiretroviral therapy (ART). The trajectory of HIV-related inflammation may vary with the timing of ART initiation. We examined immune activation markers in cerebrospinal fluid (CSF) and blood specimens collected over 96 weeks from participants who initiated ART during acute HIV infection (AHI). METHODS: RV254/SEARCH010 study participants with AHI underwent CSF (n = 89) and plasma (n = 146) sampling before initiating ART and at weeks 24 and 96 of treatment. A majority participants (64.4%) received a standard ART regimen (hereafter, "standard ART"), with some (34.7%) also receiving maraviroc and raltegravir for the first 24 weeks (hereafter, "ART plus"). We compared neopterin, CXCL10, CCL2, and interleukin 6 (IL-6) levels in the AHI group to those in 18 healthy, uninfected controls. RESULTS: Following 24 and 96 weeks of treatment, levels of all CSF markers normalized while levels of several plasma markers remained elevated in the AHI group (P < .001). Participants receiving the ART-plus regimen had lower median plasma CCL2 levels at week 24 and lower plasma neopterin levels at week 96. CONCLUSIONS: ART initiation during AHI differentially impacts the brain compartment, with markers of inflammation returning to normal levels in the CSF, where they were sustained at week 96, but not in plasma.

Screw configuration in proximal humerus plating has a significant impact on fixation failure risk predicted by finite element models.

BACKGROUND: Proximal humeral fractures occur frequently, with fixed angle locking plates often being used for their treatment. No current quantitative evidence for the effect of different screw configurations exists, and the large number of variations makes biomechanical testing prohibitive. Therefore, we used an established and validated finite element osteosynthesis test kit to quantify the effect of variations in screw configuration on predicted failure risk of PHILOS plate fixation for unstable proximal humerus fractures. METHODS: Twenty-six low-density humerus models were osteotomized to create malreduced unstable 3-part fractures that were virtually fixed with PHILOS plates. Twelve screw configurations were simulated: 6 using 2 screw rows, 4 using 3 rows, and 1 with either 8 or 9 screws. Three physiological loading cases were modeled and an established finite element analysis methodology was used. The average peri-screw bone strain, previously demonstrated to predict fatigue cutout failure, was used to compare the different configurations. RESULTS: Significant differences in peri-screw strains, and thus predicted failure risk, were seen with different combinations. The 9-screw configuration demonstrated the lowest peri-screw strains. Fewer screw constructs showed lower strains when placed further apart. The calcar screws (row E) significantly (P < .001) reduced fixation failure risk. CONCLUSION: Screw configurations significantly impact predicted cutout failure risk for locking plate fixations of unstable proximal humerus fractures in low-density bone. Although requiring clinical corroboration, the result of this study suggests that additional screws reduce peri-screw strains, the distance between them should be maximized whenever possible and the calcar screws should be used.

The influence of screw length on predicted cut-out failures for proximal humeral fracture fixations predicted by finite element simulations.

BACKGROUND: The aim of this study was to identify the effect of screw length on predictions of fixation failure in three-part proximal humeral fractures using a finite element-based osteosynthesis modelling toolkit. METHODS: A mal-reduced unstable three-part AO/OTA 11-B3.2 fracture with medial comminution was simulated in forty-two digitally processed proximal humeri covering a spectrum of bone densities and fixed with the PHILOS plate using three distal and six proximal locking screws. Four test groups were generated based on the screw tip to joint surface distance (TJD), with all proximal screws being shortened from 4 mm TJD to be 8, 12 or 16 mm TJD. Average bone strains around the screw tips, correlating with biomechanical cyclic cut-out-type failure, were evaluated in three physiological loading protocols representing simple shoulder motions. Six further groups were tested, where five of the proximal screws were inserted to 4 mm TJD and the sixth screw to 8 mm TJD. RESULTS: Exponential increases in the predicted risk of fixation failure were seen with increased tip-to-joint distances (p < 0.001). When one of the proximal screws was placed 8 mm from the joint, with the remaining five at 4 mm distance, significant increases (p < 0.001) were registered in the strains around the screw tips in all except the two superior screws. This effect was maximal around the calcar screws (p < 0.001) and for lower density samples (p < 0.001). CONCLUSIONS: These results suggest that longer screws provide reduced risk of cut-out failure, i.e. distalisation and/or varisation of the head fragment, and thus may decrease failure rates in proximal humeral fractures treated with angular stable plates. These findings require clinical corroboration and further studies to investigate the risk of screw perforation.

Negotiating Tensions between Methodology and Procedural Ethics.

In this commentary, I consider what can go wrong in research when tensions arise between methodology and procedural ethics. I recount difficulties negotiating and implementing a participant recruitment strategy during my doctoral research project, which aimed to explore the experiences of people affected by dementia in the United Kingdom who were disengaged from services. To access this hard-to-reach population, I intended to adopt an informal recruitment strategy, snowball sampling from personal contacts and striking up conversations in public places. The procedural ethics committee were unhappy with this approach, deeming it potentially coercive. They suggested a more formal recruitment strategy enacted via emailing community organisations and churches. This approach entailed practical consequences that ultimately weakened the study sample, data and findings. This case raises questions about the negotiation of tensions between methodology and procedural ethics in gerontological research.