Validated machine learning tools to distinguish immune checkpoint inhibitor, radiotherapy, COVID-19 and other infective pneumonitis.

BACKGROUND: Pneumonitis is a well-described, potentially disabling, or fatal adverse effect associated with both immune checkpoint inhibitors (ICI) and thoracic radiotherapy. Accurate differentiation between checkpoint inhibitor pneumonitis (CIP) radiation pneumonitis (RP), and infective pneumonitis (IP) is crucial for swift, appropriate, and tailored management to achieve optimal patient outcomes. However, correct diagnosis is often challenging, owing to overlapping clinical presentations and radiological patterns. METHODS: In this multi-centre study of 455 patients, we used machine learning with radiomic features extracted from chest CT imaging to develop and validate five models to distinguish CIP and RP from COVID-19, non-COVID-19 infective pneumonitis, and each other. Model performance was compared to that of two radiologists. RESULTS: Models to distinguish RP from COVID-19, CIP from COVID-19 and CIP from non-COVID-19 IP out-performed radiologists (test set AUCs of 0.92 vs 0.8 and 0.8; 0.68 vs 0.43 and 0.4; 0.71 vs 0.55 and 0.63 respectively). Models to distinguish RP from non-COVID-19 IP and CIP from RP were not superior to radiologists but demonstrated modest performance, with test set AUCs of 0.81 and 0.8 respectively. The CIP vs RP model performed less well on patients with prior exposure to both ICI and radiotherapy (AUC 0.54), though the radiologists also had difficulty distinguishing this test cohort (AUC values 0.6 and 0.6). CONCLUSION: Our results demonstrate the potential utility of such tools as a second or concurrent reader to support oncologists, radiologists, and chest physicians in cases of diagnostic uncertainty. Further research is required for patients with exposure to both ICI and thoracic radiotherapy.

Peripheral nerve stimulation for chronic knee pain following total knee arthroplasty: a systematic review.

Chronic knee pain following total knee arthroplasty (TKA) affects a subset of patients that is refractory to pharmacological and non-pharmacological modalities. Peripheral nerve stimulation (PNS) has been used in patients with chronic knee pain following TKA and has shown some efficacy. Methods: Comprehensive search of Ovid Medline, Elsevier Embase, Cochrane Central Register of Controlled Trials, CINAHL Plus with Full Text, Scopus, SPORTDiscus with Full Text and the Web of Science platform. From inception to August 2022, for studies using PNS to treat chronic knee pain following TKA. Primary outcomes included pain scores, functional status and medication usage. Results: Nine studies were extrapolated with all demonstrating effectiveness of PNS for patients with chronic knee pain following TKA. Discussion: PNS for chronic knee pain following TKA has been shown to be an efficacious treatment modality. The level of evidence is low and more research is needed to assess its safety and effectiveness.

A Novel Radiogenomics Biomarker for Predicting Treatment Response and Pneumotoxicity From Programmed Cell Death Protein or Ligand-1 Inhibition Immunotherapy in NSCLC.

INTRODUCTION: Patient selection for checkpoint inhibitor immunotherapy is currently guided by programmed death-ligand 1 (PD-L1) expression obtained from immunohistochemical staining of tumor tissue samples. This approach is susceptible to limitations resulting from the dynamic and heterogeneous nature of cancer cells and the invasiveness of the tissue sampling procedure. To address these challenges, we developed a novel computed tomography (CT) radiomic-based signature for predicting disease response in patients with NSCLC undergoing programmed cell death protein 1 (PD-1) or PD-L1 checkpoint inhibitor immunotherapy. METHODS: This retrospective study comprises a total of 194 patients with suitable CT scans out of 340. Using the radiomic features computed from segmented tumors on a discovery set of 85 contrast-enhanced chest CTs of patients diagnosed with having NSCLC and their CD274 count, RNA expression of the protein-encoding gene for PD-L1, as the response vector, we developed a composite radiomic signature, lung cancer immunotherapy-radiomics prediction vector (LCI-RPV). This was validated in two independent testing cohorts of 66 and 43 patients with NSCLC treated with PD-1 or PD-L1 inhibition immunotherapy, respectively. RESULTS: LCI-RPV predicted PD-L1 positivity in both NSCLC testing cohorts (area under the curve [AUC] = 0.70, 95% confidence interval [CI]: 0.57-0.84 and AUC = 0.70, 95% CI: 0.46-0.94). In one cohort, it also demonstrated good prediction of cases with high PD-L1 expression exceeding key treatment thresholds (>50%: AUC = 0.72, 95% CI: 0.59-0.85 and >90%: AUC = 0.66, 95% CI: 0.45-0.88), the tumor's objective response to treatment at 3 months (AUC = 0.68, 95% CI: 0.52-0.85), and pneumonitis occurrence (AUC = 0.64, 95% CI: 0.48-0.80). LCI-RPV achieved statistically significant stratification of the patients into a high- and low-risk survival group (hazard ratio = 2.26, 95% CI: 1.21-4.24, p = 0.011 and hazard ratio = 2.45, 95% CI: 1.07-5.65, p = 0.035). CONCLUSIONS: A CT radiomics-based signature developed from response vector CD274 can aid in evaluating patients' suitability for PD-1 or PD-L1 checkpoint inhibitor immunotherapy in NSCLC.

A radiomics-based decision support tool improves lung cancer diagnosis in combination with the Herder score in large lung nodules.

BACKGROUND: Large lung nodules (≥15 mm) have the highest risk of malignancy, and may exhibit important differences in phenotypic or clinical characteristics to their smaller counterparts. Existing risk models do not stratify large nodules well. We aimed to develop and validate an integrated segmentation and classification pipeline, incorporating deep-learning and traditional radiomics, to classify large lung nodules according to cancer risk. METHODS: 502 patients from five U.K. centres were recruited to the large-nodule arm of the retrospective LIBRA study between July 2020 and April 2022. 838 CT scans were used for model development, split into training and test sets (70% and 30% respectively). An nnUNet model was trained to automate lung nodule segmentation. A radiomics signature was developed to classify nodules according to malignancy risk. Performance of the radiomics model, termed the large-nodule radiomics predictive vector (LN-RPV), was compared to three radiologists and the Brock and Herder scores. FINDINGS: 499 patients had technically evaluable scans (mean age 69 ± 11, 257 men, 242 women). In the test set of 252 scans, the nnUNet achieved a DICE score of 0.86, and the LN-RPV achieved an AUC of 0.83 (95% CI 0.77-0.88) for malignancy classification. Performance was higher than the median radiologist (AUC 0.75 [95% CI 0.70-0.81], DeLong p = 0.03). LN-RPV was robust to auto-segmentation (ICC 0.94). For baseline solid nodules in the test set (117 patients), LN-RPV had an AUC of 0.87 (95% CI 0.80-0.93) compared to 0.67 (95% CI 0.55-0.76, DeLong p = 0.002) for the Brock score and 0.83 (95% CI 0.75-0.90, DeLong p = 0.4) for the Herder score. In the international external test set (n = 151), LN-RPV maintained an AUC of 0.75 (95% CI 0.63-0.85). 18 out of 22 (82%) malignant nodules in the Herder 10-70% category in the test set were identified as high risk by the decision-support tool, and may have been referred for earlier intervention. INTERPRETATION: The model accurately segments and classifies large lung nodules, and may improve upon existing clinical models. FUNDING: This project represents independent research funded by: 1) Royal Marsden Partners Cancer Alliance, 2) the Royal Marsden Cancer Charity, 3) the National Institute for Health Research (NIHR) Biomedical Research Centre at the Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, London, 4) the National Institute for Health Research (NIHR) Biomedical Research Centre at Imperial College London, 5) Cancer Research UK (C309/A31316).

Healthy aging impairs face discrimination ability.

Face images enable individual identities to be discriminated from one another. We aimed to quantify age-related changes in different aspects of face identity discrimination. Face discrimination sensitivity was measured with a memory-free "odd-one-out" task. Five age groups (N = 15) of healthy adults with normal vision were tested: 20, 50-59, 60-69, 70-79, and 80-89. Sensitivity was measured for full-face images (all features visible), external features (head-shape, hairline), internal features (nose, mouth, eyes, and eyebrows) and closed-contour shapes (control object). Sensitivity to full-faces continuously declined by approximately 13% per decade, after 50 years of age. When age-related differences in visual acuity were controlled, the effect of age on face discrimination sensitivity remained. Sensitivity to face features also deteriorated with age. Although the effect for external features was similar to full-faces, the rate of decline was considerably steeper (approximately 3.7 times) for internal, relative to external, features. In contrast, there was no effect of age on sensitivity to shapes. All age groups demonstrated the same overall pattern of sensitivity to different types of face information. Healthy aging was associated with a continuous decline in sensitivity to both full-faces and face features, although encoding of internal features was disproportionately impaired. This age-related deficit was independent of differences in low-level vision. That sensitivity to shapes was unaffected by age suggests these results cannot be explained by general cognitive decline or lower-level visual deficits. Instead, healthy aging is associated with a specific decline in the mechanisms that underlie face discrimination.

A 4-year study of the use of the short metacarpal cast in the management of metacarpal shaft fractures.

We report on our experience of using a short, moulded metacarpal cast over a 4-year period in the non-surgical management of metacarpal shaft fractures. Between 6 April 2015 and 6 April 2019, 117 patients were treated using this method. The majority were male, and the mean age was 24.6 years. The most common mechanism of injury was a punch injury (73 patients, 62%). Fifteen patients (13%) were treated for multiple metacarpal fractures. Immediately after cast removal, 68% had a full range of finger movement and 68% were pain free. Few required formal hand therapy. Fifteen patients experienced minor complications, primarily soft tissue irritation from the cast and non-limiting extensor lag. The moulded short metacarpal cast is an effective non-surgical treatment for angulated extra-articular metacarpal fractures of the diaphysis and diametaphyseal junction.Level of evidence: IV.

In the Blink of an Eye: Reading Mental States From Briefly Presented Eye Regions.

Faces provide not only cues to an individual's identity, age, gender, and ethnicity but also insight into their mental states. The aim was to investigate the temporal aspects of processing of facial expressions of complex mental states for very short presentation times ranging from 12.5 to 100 ms in a four-alternative forced choice paradigm based on Reading the Mind in the Eyes test. Results show that participants are able to recognise very subtle differences between facial expressions; performance is better than chance, even for the shortest presentation time. Importantly, we show for the first time that observers can recognise these expressions based on information contained in the eye region only. These results support the hypothesis that the eye region plays a particularly important role in social interactions and that the expressions in the eyes are a rich source of information about other peoples' mental states. When asked to what extent the observers guessed during the task, they significantly underestimated their ability to make correct decisions, yet perform better than chance, even for very brief presentation times. These results are particularly relevant in the light of the current COVID-19 pandemic and the associated wearing of face coverings.

Surgery versus cast immobilisation for adults with a bicortical fracture of the scaphoid waist (SWIFFT): a pragmatic, multicentre, open-label, randomised superiority trial.

BACKGROUND: Scaphoid fractures account for 90% of carpal fractures and occur predominantly in young men. The use of immediate surgical fixation to manage this type of fracture has increased, despite insufficient evidence of improved outcomes over non-surgical management. The SWIFFT trial compared the clinical effectiveness of surgical fixation with cast immobilisation and early fixation of fractures that fail to unite in adults with scaphoid waist fractures displaced by 2 mm or less. METHODS: This pragmatic, parallel-group, multicentre, open-label, two-arm, randomised superiority trial included adults (aged 16 years or older) who presented to orthopaedic departments of 31 hospitals in England and Wales with a clear bicortical fracture of the scaphoid waist on radiographs. An independent remote randomisation service used a computer-generated allocation sequence with randomly varying block sizes to randomly assign participants (1:1) to receive either early surgical fixation (surgery group) or below-elbow cast immobilisation followed by immediate fixation if non-union of the fracture was confirmed (cast immobilisation group). Randomisation was stratified by whether or not there was displacement of either a step or a gap of 1-2 mm inclusive on any radiographic view. The primary outcome was the total patient-rated wrist evaluation (PRWE) score at 52 weeks after randomisation, and it was analysed on an available case intention-to-treat basis. This trial is registered with the ISRCTN registry, ISRCTN67901257, and is no longer recruiting, but long-term follow-up is ongoing. FINDINGS: Between July 23, 2013, and July 26, 2016, 439 (42%) of 1047 assessed patients (mean age 33 years; 363 [83%] men) were randomly assigned to the surgery group (n=219) or to the cast immobilisation group (n=220). Of these, 408 (93%) participants were included in the primary analysis (203 participants in the surgery group and 205 participants in the cast immobilisation group). 16 participants in the surgery group and 15 participants in the cast immobilisation group were excluded because of either withdrawal, no response, or no follow-up data at 6, 12, 26, or 52 weeks. There was no significant difference in mean PRWE scores at 52 weeks between the surgery group (adjusted mean 11·9 [95% CI 9·2-14·5]) and the cast immobilisation group (14·0 [11·3 to 16·6]; adjusted mean difference -2·1 [95% CI -5·8 to 1·6], p=0·27). More participants in the surgery group (31 [14%] of 219 participants) had a potentially serious complication from surgery than in the cast immobilisation group (three [1%] of 220 participants), but fewer participants in the surgery group (five [2%]) had cast-related complications than in the cast immobilisation group (40 [18%]). The number of participants who had a medical complication was similar between the two groups (four [2%] in the surgery group and five [2%] in the cast immobilisation group). INTERPRETATION: Adult patients with scaphoid waist fractures displaced by 2 mm or less should have initial cast immobilisation, and any suspected non-unions should be confirmed and immediately fixed with surgery. This treatment strategy will help to avoid the risks of surgery and mostly limit the use of surgery to fixing fractures that fail to unite. FUNDING: National Institute for Health Research Health Technology Assessment Programme.

The Effect of Age-Related Macular Degeneration on Components of Face Perception.

Purpose: Patients with age-related macular degeneration (AMD) experience difficulty with discriminating between faces. We aimed to use a new clinical test to quantify the impact of AMD on face perception and to determine the specific aspects that are affected. Methods: The Caledonian face test uses an adaptive procedure to measure face discrimination thresholds: the minimum difference required between faces for reliable discrimination. Discrimination thresholds were measured for full-faces, external features (head-shape and hairline), internal features (nose, mouth, eyes, and eyebrows) and shapes (non-face task). Participants were 20 patients with dry AMD (logMAR VA = 0.14 to 0.62), 20 patients with wet AMD (0.10 to 0.60), and 20 age-matched control subjects (-0.18 to +0.06). Results: Relative to controls, full-face discrimination thresholds were, on average, 1.76 and 1.73 times poorer in participants with dry and wet AMD, respectively. AMD also reduced sensitivity to face features, but discrimination of the internal, relative to external, features was disproportionately impaired. Both distance VA and contrast sensitivity were significant independent predictors of full-face discrimination thresholds (R2 = 0.66). Sensitivity to full-faces declined by a factor of approximately 1.19 per 0.1 logMAR reduction in VA. Conclusions: Both dry and wet AMD significantly reduce sensitivity to full-faces and their component parts to similar extents. Distance VA and contrast sensitivity are closely associated with face discrimination sensitivity. These results quantify the extent of sensitivity impairment in patients with AMD and predict particular difficulty in everyday tasks that rely on internal feature information, including recognition of familiar faces and facial expressions.

Quantifying the effect of viewpoint changes on sensitivity to face identity.

Although faces can be recognized from different viewpoints, variations in viewpoint impair face identification ability. The present study quantified the effect of changes in viewpoint on sensitivity to face identity. We measured discrimination thresholds for synthetic faces presented from several viewpoints (same viewpoint condition) and the same faces shown with a change in viewpoint (5°, 10° or 20°) between viewing and test. We investigated three types of viewpoint change: (i) front-to-side (front-view matched to 20°° side-view), (ii) side-to-front (20° side-view matched to front) and (iii) symmetrical (10° left to 10° right). In the same viewpoint condition, discrimination thresholds were lowest for faces presented from 0° and increased linearly as the viewing angle was increased (threshold elevations: 0°â€¯= 1.00×, 5°â€¯= 1.11×, 10°â€¯= 1.22×, 20°â€¯= 1.69×). Changes in viewpoint between viewing and test led to further reductions in discrimination sensitivity, which depended upon the magnitude of viewpoint change (5°â€¯= 1.38×, 10°â€¯= 1.75×, 20°â€¯= 2.07×). Sensitivity also depended upon the type of viewpoint change: while a 20° front-to-side viewpoint change increased discrimination thresholds by a factor of 2.09×, a symmetrical change in viewpoint, of the same magnitude, did not significantly reduce sensitivity (1.26×). Sensitivity to face identity is significantly reduced by changes in viewpoint. Factors which determine the extent of this reduction include the magnitude of viewpoint change and symmetry. Our results support the premise of viewpoint-dependent encoding of unfamiliar face identities, and suggest that symmetry may be used to recognize identities across different viewpoints.

From individual features to full faces: Combining aspects of face information.

We investigated how information from face features is combined by comparing sensitivity to individual features with that for external (head shape, hairline) and internal (nose, mouth, eyes, eyebrows) feature compounds. Discrimination thresholds were measured for synthetic faces under the following conditions: (a) full-faces; (b) individual features (e.g., nose); and (c) feature compounds (either external or internal). Individual features and feature compounds were presented both in isolation and embedded within a fixed, task irrelevant face context. Relative to the full-face baseline, threshold elevations for the internal feature compound (2.41x) were comparable to those for the most sensitive individual feature (nose = 2.12x). External features demonstrated the same pattern. A model that incorporated all available feature information within a single channel in an efficient way overestimated sensitivity to feature compounds. Embedding individual features within a task-irrelevant context reduced discrimination sensitivity, relative to isolated presentation. Sensitivity to feature compounds, however, was unaffected by embedding. A loss of sensitivity when embedding features within a fixed-face context is consistent with holistic processing, which limits access to information about individual features. However, holistic combination of information across face features is not efficient: Sensitivity to feature compounds is no better than sensitivity to the best individual feature. No effect of embedding internal feature compounds within task-irrelevant external face features (or vice versa) suggests that external and internal features are processed independently.

Contributions of individual face features to face discrimination.

Faces are highly complex stimuli that contain a host of information. Such complexity poses the following questions: (a) do observers exhibit preferences for specific information? (b) how does sensitivity to individual face parts compare? These questions were addressed by quantifying sensitivity to different face features. Discrimination thresholds were determined for synthetic faces under the following conditions: (i) 'full face': all face features visible; (ii) 'isolated feature': single feature presented in isolation; (iii) 'embedded feature': all features visible, but only one feature modified. Mean threshold elevations for isolated features, relative to full-faces, were 0.84x, 1.08, 2.12, 3.34, 4.07 and 4.47 for head-shape, hairline, nose, mouth, eyes and eyebrows respectively. Hence, when two full faces can be discriminated at threshold, the difference between the eyes is about four times less than what is required when discriminating between isolated eyes. In all cases, sensitivity was higher when features were presented in isolation than when they were embedded within a face context (threshold elevations of 0.94x, 1.74, 2.67, 2.90, 5.94 and 9.94). This reveals a specific pattern of sensitivity to face information. Observers are between two and four times more sensitive to external than internal features. The pattern for internal features (higher sensitivity for the nose, compared to mouth, eyes and eyebrows) is consistent with lower sensitivity for those parts affected by facial dynamics (e.g. facial expressions). That isolated features are easier to discriminate than embedded features supports a holistic face processing mechanism which impedes extraction of information about individual features from full faces.

Timing of Allergenic Food Introduction to the Infant Diet and Risk of Allergic or Autoimmune Disease: A Systematic Review and Meta-analysis.

IMPORTANCE: Timing of introduction of allergenic foods to the infant diet may influence the risk of allergic or autoimmune disease, but the evidence for this has not been comprehensively synthesized. OBJECTIVE: To systematically review and meta-analyze evidence that timing of allergenic food introduction during infancy influences risk of allergic or autoimmune disease. DATA SOURCES: MEDLINE, EMBASE, Web of Science, CENTRAL, and LILACS databases were searched between January 1946 and March 2016. STUDY SELECTION: Intervention trials and observational studies that evaluated timing of allergenic food introduction during the first year of life and reported allergic or autoimmune disease or allergic sensitization were included. DATA EXTRACTION AND SYNTHESIS: Data were extracted in duplicate and synthesized for meta-analysis using generic inverse variance or Mantel-Haenszel methods with a random-effects model. GRADE was used to assess the certainty of evidence. MAIN OUTCOMES AND MEASURES: Wheeze, eczema, allergic rhinitis, food allergy, allergic sensitization, type 1 diabetes mellitus, celiac disease, inflammatory bowel disease, autoimmune thyroid disease, and juvenile rheumatoid arthritis. RESULTS: Of 16 289 original titles screened, data were extracted from 204 titles reporting 146 studies. There was moderate-certainty evidence from 5 trials (1915 participants) that early egg introduction at 4 to 6 months was associated with reduced egg allergy (risk ratio [RR], 0.56; 95% CI, 0.36-0.87; I2 = 36%; P = .009). Absolute risk reduction for a population with 5.4% incidence of egg allergy was 24 cases (95% CI, 7-35 cases) per 1000 population. There was moderate-certainty evidence from 2 trials (1550 participants) that early peanut introduction at 4 to 11 months was associated with reduced peanut allergy (RR, 0.29; 95% CI, 0.11-0.74; I2 = 66%; P = .009). Absolute risk reduction for a population with 2.5% incidence of peanut allergy was 18 cases (95% CI, 6-22 cases) per 1000 population. Certainty of evidence was downgraded because of imprecision of effect estimates and indirectness of the populations and interventions studied. Timing of egg or peanut introduction was not associated with risk of allergy to other foods. There was low- to very low-certainty evidence that early fish introduction was associated with reduced allergic sensitization and rhinitis. There was high-certainty evidence that timing of gluten introduction was not associated with celiac disease risk, and timing of allergenic food introduction was not associated with other outcomes. CONCLUSIONS AND RELEVANCE: In this systematic review, early egg or peanut introduction to the infant diet was associated with lower risk of developing egg or peanut allergy. These findings must be considered in the context of limitations in the primary studies.

Comparison of Muscle Onset Activation Sequences between a Golf or Tennis Swing and Common Training Exercises Using Surface Electromyography: A Pilot Study.

Aim. The purpose of this pilot study is to use surface electromyography to determine an individual athlete's typical muscle onset activation sequence when performing a golf or tennis forward swing and to use the method to assess to what degree the sequence is reproduced with common conditioning exercises and a machine designed for this purpose. Methods. Data for 18 healthy male subjects were collected for 15 muscles of the trunk and lower extremities. Data were filtered and processed to determine the average onset of muscle activation for each motion. A Spearman correlation estimated congruence of activation order between the swing and each exercise. Correlations of each group were pooled with 95% confidence intervals using a random effects meta-analytic strategy. Results. The averaged sequences differed among each athlete tested, but pooled correlations demonstrated a positive association between each exercise and the participants' natural muscle onset activation sequence. Conclusion. The selected training exercises and Turning Point™ device all partially reproduced our athletes' averaged muscle onset activation sequences for both sports. The results support consideration of a larger, adequately powered study using this method to quantify to what degree each of the selected exercises is appropriate for use in both golf and tennis.

Rare and unusual clinicopathologic presentation of renal AL amyloidosis.

Rarely, renal light chain (AL) amyloidosis may present without significant proteinuria owing to glomerular sparing and amyloid deposition confined to the vasculature and tubulointerstitium.

The Caledonian face test: A new test of face discrimination.

This study aimed to develop a clinical test of face perception which is applicable to a wide range of patients and can capture normal variability. The Caledonian face test utilises synthetic faces which combine simplicity with sufficient realism to permit individual identification. Face discrimination thresholds (i.e. minimum difference between faces required for accurate discrimination) were determined in an "odd-one-out" task. The difference between faces was controlled by an adaptive QUEST procedure. A broad range of face discrimination sensitivity was determined from a group (N=52) of young adults (mean 5.75%; SD 1.18; range 3.33-8.84%). The test is fast (3-4 min), repeatable (test-re-test r(2)=0.795) and demonstrates a significant inversion effect. The potential to identify impairments of face discrimination was evaluated by testing LM who reported a lifelong difficulty with face perception. While LM's impairment for two established face tests was close to the criterion for significance (Z-scores of -2.20 and -2.27) for the Caledonian face test, her Z-score was -7.26, implying a more than threefold higher sensitivity. The new face test provides a quantifiable and repeatable assessment of face discrimination ability. The enhanced sensitivity suggests that the Caledonian face test may be capable of detecting more subtle impairments of face perception than available tests.

Estimated age and gender profile of individuals missed by a home-based HIV testing and counselling campaign in a Botswana community.

INTRODUCTION: It would be useful to understand which populations are not reached by home-based HIV-1 testing and counselling (HTC) to improve strategies aimed at linking these individuals to care and reducing rates of onward HIV transmission. METHODS: We present the results of a baseline home-based HTC (HBHTC) campaign aimed at counselling and testing residents aged 16 to 64 for HIV in the north-eastern sector of Mochudi, a community in Botswana with about 44,000 inhabitants. Collected data were compared with population references for Botswana, the United Nations (UN) estimates based on the National Census data and the Botswana AIDS Impact Survey IV (BAIS-IV). Analyzed data and references were stratified by age and gender. RESULTS: A total of 6238 age-eligible residents were tested for HIV-1; 1247 (20.0%; 95% CI 19.0 to 21.0%) were found to be HIV positive (23.7% of women vs. 13.4% of men). HIV-1 prevalence peaked at 44% in 35- to 39-year-old women and 32% in 40- to 44-year-old men. A lower HIV prevalence rate, 10.9% (95% CI 9.5 to 12.5%), was found among individuals tested for the first time. A significant gender gap was evident in all analyzed subsets. The existing HIV transmission network was analyzed by combining phylogenetic mapping and household structure. Between 62.4 and 71.8% of all HIV-positive individuals had detectable virus. When compared with the UN and BAIS-IV estimates, the proportion of men missed by the testing campaign (48.5%; 95% CI 47.0 to 50.0%) was significantly higher than the proportion of missed women (14.2%; 95% CI 13.2 to 15.3%; p<0.0001). The estimated proportion of missed men peaked at about 60% in the age group 30 to 39 years old. The proportions of missed women were substantially smaller, at approximately 28% within the age groups 30 to 34 and 45 to 49 years old. CONCLUSIONS: The HBHTC campaign seems to be an efficient tool for reaching individuals who have never been tested previously in southern African communities. However, about half of men from 16 to 64 years old were not reached by the HBHTC, including about 60% of men between 30 and 40 years old. Alternative HTC strategies should be developed to bring these men to care, which will contribute to reduction of HIV incidence in communities.

Distinct lower visual field preference for object shape.

Humans manipulate objects chiefly within their lower visual field, a consequence of upright posture and the anatomical position of hands and arms.This study tested the hypothesis of enhanced sensitivity to a range of stimuli within the lower visual field. Following current models of hierarchical processing within the ventral steam, discrimination sensitivity was measured for orientation, curvature, shape (radial frequency patterns), and faces at various para-central locations (horizontal, vertical, and main diagonal meridians) and eccentricities (5° and 10°). Peripheral sensitivity was isotropic for orientation and curvature. By contrast, observers were significantly better at discriminating shapes throughout the lower visual field compared to elsewhere. For faces, however, peak sensitivity was found in the left visual field, corresponding to the right hemispheric localization of human face processing. Presenting head outlines without any internal features (e.g., eyes, mouth) recovered the lower visual field advantage found for simple shapes. A lower visual field preference for the shape of an object, which is absent for more localized information (orientation and curvature) but also for more complex objects (faces), is inconsistent with a strictly feed-forward model and poses a challenge for multistage models of object perception. The distinct lower visual field preference for contour shapes is, however, consistent with an asymmetry at intermediate stages of visual processing, which may play a key role in representing object characteristics that are particularly relevant to visually guided actions.

Ulna Nerve Decompression at the Elbow in Patients with Normal Nerve Conduction Tests.

BACKGROUND: Ulna nerve compression at the elbow is the second most common neuropathy of the upper limb. It has been suggested that nerve conduction tests are required to correctly make the diagnosis. The aim of this study was to assess whether patients with normal nerve conduction testing benefitted from surgical release of the ulna nerve. METHODS: 56 patients with symptoms of ulna nerve compression at the elbow were evaluated prospectively. All patients underwent electrophysiology testing followed by ulna nerve decompression irrespective of the results of the electrophysiology testing. Functional scores using the QuickDASH and PEM score were collected up to 12 months post-surgery. RESULTS: No difference was found between the group with normal and the group with abnormal electrophysiology studies. CONCLUSIONS: We conclude that patients who clinically have ulna nerve compression still benefit from ulna nerve decompression despite normal nerve conduction tests.

Microbial response to single-cell protein production and brewery wastewater treatment.

As global fisheries decline, microbial single-cell protein (SCP) produced from brewery process water has been highlighted as a potential source of protein for sustainable animal feed. However, biotechnological investigation of SCP is difficult because of the natural variation and complexity of microbial ecology in wastewater bioreactors. In this study, we investigate microbial response across a full-scale brewery wastewater treatment plant and a parallel pilot bioreactor modified to produce an SCP product. A pyrosequencing survey of the brewery treatment plant showed that each unit process selected for a unique microbial community. Notably, flow equalization basins were dominated by Prevotella, methanogenesis effluent had the highest levels of diversity, and clarifier wet-well samples were sources of sequences for the candidate bacterial phyla of TM7 and BD1-5. Next, the microbial response of a pilot bioreactor producing SCP was tracked over 1 year, showing that two different production trials produced two different communities originating from the same starting influent. However, SCP production resulted generally in enrichment of several clades of rhizospheric diazotrophs of Alphaproteobacteria and Betaproteobacteria in the bioreactor and even more so in the final product. These diazotrophs are potentially useful as the basis of a SCP product for commercial feed production.