A comparison of the physiological consequences of head-loading and back-loading for African and European women

The aim is to quantify the physiological cost of head-load carriage and to examine the ‘free ride’ hypothesis for head-load carriage in groups of women differing in their experience of head-loading. Twenty-four Xhosa women [13 experienced head-loaders (EXP), 11 with no experience of head-loading (NON)] attempted to carry loads of up to 70% of body mass on both their heads and backs whilst walking on a treadmill at a self-selected walking speed. Expired air was collected throughout. In a second study nine women, members of the British Territorial Army, carried similar loads, again at a self-selected speed. Maximum load carried was greater for the back than the head (54.7 ± 15.1 vs. 40.8 ± 13.2% BM, P <0.0005). Considering study one, head-loading required a greater oxygen rate than back-loading (10.1 ± 2.6 vs. 8.8 ± 2.3 ml kg bodymass−1 min−1, P = 0.043, for loads 10–25% BM) regardless of previous head-loading experience (P = 0.333). Percentage changes in oxygen consumption associated with head-loading were greater than the proportional load added in both studies but were smaller than the added load for the lighter loads carried on the back in study 1. All other physiological variables were consistent with changes in oxygen consumption. The data provides no support for the ‘free ride’ hypothesis for head-loading although there is some evidence of energy saving mechanisms for back-loading at low speed/load combinations. Investigating the large individual variation in response may help in identifying combinations of factors that contribute to improved economy

Dynamical Casimir effect with Dirichlet and Neumann boundary conditions

We derive the radiation pressure force on a non-relativistic moving plate in 1+1 dimensions. We assume that a massless scalar field satisfies either Dirichlet or Neumann boundary conditions (BC) at the instantaneous position of the plate. We show that when the state of the field is invariant under time translations, the results derived for Dirichlet and Neumann BC are equal. We discuss the force for a thermal field state as an example for this case. On the other hand, a coherent state introduces a phase reference, and the two types of BC lead to different results.Comment: 12 page

Chronic digital infection presenting with gross enlargement of the toes: two case reports and review of the literature

There are many conditions ranging from the benign to the malignant, which can present with enlargement of one or more digits. An understanding of the differential diagnosis is important such that the potentially serious aetiologies are not missed and patients can therefore be treated appropriately

The clinical presentation of monkeypox: a retrospective case-control study of patients with possible or probable monkeypox in a West London cohort

Objectives: Since May 2022, cases of human monkeypox virus (hMPXV) with human-to-human cross-transmission have significantly increased in non-endemic countries. Our aim was to characterise diagnostic features of patients with confirmed and possible monkeypox to guide future risk stratification, and to describe a virtual care model. Methods: We performed a retrospective case-control study of 140 patients assessed and screened for suspected monkeypox; on hMPXV PCR testing, 70 were confirmed positive and 70 negative. Data were compared to generate odds ratios of demographic and clinical features. Results: Positive patients were predominantly cis-male (99%) and self-identified as gay, bisexual and other men who have sex with men (GBMSM) (94%). Lymphadenopathy at presentation was associated with a higher likelihood of a positive result (OR 7.69 [95% CI 3.58, 16.51]). Positive patients were more likely to have a rash affecting the genital (OR 5.38 [95% CI 2.57, 11.23]) or buttocks/perianal region (OR 3.79 [1.70, 8.45]) compared with negative controls. 79% of patients engaged with virtual ward follow-up. Conclusions: These data can inform a risk-based approach to management of suspected monkeypox in GBMSM populations. Lymphadenopathy at presentation and the location of the rash were more associated with a positive hMPXV result. Health authorities can consider a virtual ward approach in the hMPXV outbreak

Spatial variation in the fine-structure constant -- new results from VLT/UVES

(abridged) We present a new analysis of a large sample of quasar absorption-line spectra obtained using UVES (the Ultraviolet and Visual Echelle Spectrograph) on the VLT (Very Large Telescope) in Chile. In the VLT sample (154 absorbers), we find evidence that alpha increases with increasing cosmological distance from Earth. However, as previously shown, the Keck sample (141 absorbers) provided evidence for a smaller alpha in the distant absorption clouds. Upon combining the samples an apparent variation of alpha across the sky emerges which is well represented by an angular dipole model pointing in the direction RA=(17.3 +/- 1.0) hr, dec. = (-61 +/- 10) deg, with amplitude (0.97 +0.22/-0.20) x 10^(-5). The dipole model is required at the 4.1 sigma statistical significance level over a simple monopole model where alpha is the same across the sky (but possibly different to the current laboratory value). The data sets reveal a number of remarkable consistencies: various data cuts are consistent and there is consistency in the overlap region of the Keck and VLT samples. Assuming a dipole-only (i.e. no-monopole) model whose amplitude grows proportionally with `lookback-time distance' (r=ct, where t is the lookback time), the amplitude is (1.1 +/- 0.2) x 10^(-6) GLyr^(-1) and the model is significant at the 4.2 sigma confidence level over the null model [Delta alpha]/alpha = 0). We apply robustness checks and demonstrate that the dipole effect does not originate from a small subset of the absorbers or spectra. We present an analysis of systematic effects, and are unable to identify any single systematic effect which can emulate the observed variation in alpha.Comment: 47 pages, 35 figures. Accepted for publication by Monthly Notices of the Royal Astronomical Society. Please see http://astronomy.swin.edu.au/~mmurphy/pub.html for an ASCII version of table A1 and the full set of Voigt profile fits for appendix

Pooled sputum to optimise the efficiency and utility of rapid, point-of-care molecular SARS-CoV-2 testing

Background As SARS-CoV-2 testing expands, particularly to widespread asymptomatic testing, high sensitivity point-of-care PCR platforms may optimise potential benefits from pooling multiple patients’ samples. Method We tested patients and asymptomatic citizens for SARS-CoV-2, exploring the efficiency and utility of CovidNudge (i) for detection in individuals’ sputum (compared to nasopharyngeal swabs), (ii) for detection in pooled sputum samples, and (iii) by modelling roll out scenarios for pooled sputum testing. Results Across 295 paired samples, we find no difference (p = 0.1236) in signal strength for sputum (mean amplified replicates (MAR) 25.2, standard deviation (SD) 14.2, range 0–60) compared to nasopharyngeal swabs (MAR 27.8, SD 12.4, range 6–56). At 10-sample pool size we find some drop in absolute strength of signal (individual sputum MAR 42.1, SD 11.8, range 13–60 vs. pooled sputum MAR 25.3, SD 14.6, range 1–54; p < 0.0001), but only marginal drop in sensitivity (51/53,96%). We determine a limit of detection of 250 copies/ml for an individual test, rising only four-fold to 1000copies/ml for a 10-sample pool. We find optimal pooled testing efficiency to be a 12–3-1-sample model, yet as prevalence increases, pool size should decrease; at 5% prevalence to maintain a 75% probability of negative first test, 5-sample pools are optimal. Conclusion We describe for the first time the use of sequentially dipped sputum samples for rapid pooled point of care SARS-CoV-2 PCR testing. The potential to screen asymptomatic cohorts rapidly, at the point-of-care, with PCR, offers the potential to quickly identify and isolate positive individuals within a population “bubble”

Genomic Profiling of Submucosal-Invasive Gastric Cancer by Array-Based Comparative Genomic Hybridization

Genomic copy number aberrations (CNAs) in gastric cancer have already been extensively characterized by array comparative genomic hybridization (array CGH) analysis. However, involvement of genomic CNAs in the process of submucosal invasion and lymph node metastasis in early gastric cancer is still poorly understood. In this study, to address this issue, we collected a total of 59 tumor samples from 27 patients with submucosal-invasive gastric cancers (SMGC), analyzed their genomic profiles by array CGH, and compared them between paired samples of mucosal (MU) and submucosal (SM) invasion (23 pairs), and SM invasion and lymph node (LN) metastasis (9 pairs). Initially, we hypothesized that acquisition of specific CNA(s) is important for these processes. However, we observed no significant difference in the number of genomic CNAs between paired MU and SM, and between paired SM and LN. Furthermore, we were unable to find any CNAs specifically associated with SM invasion or LN metastasis. Among the 23 cases analyzed, 15 had some similar pattern of genomic profiling between SM and MU. Interestingly, 13 of the 15 cases also showed some differences in genomic profiles. These results suggest that the majority of SMGCs are composed of heterogeneous subpopulations derived from the same clonal origin. Comparison of genomic CNAs between SMGCs with and without LN metastasis revealed that gain of 11q13, 11q14, 11q22, 14q32 and amplification of 17q21 were more frequent in metastatic SMGCs, suggesting that these CNAs are related to LN metastasis of early gastric cancer. In conclusion, our data suggest that generation of genetically distinct subclones, rather than acquisition of specific CNA at MU, is integral to the process of submucosal invasion, and that subclones that acquire gain of 11q13, 11q14, 11q22, 14q32 or amplification of 17q21 are likely to become metastatic

Tamoxifen resistance in early breast cancer: statistical modelling of tissue markers to improve risk prediction

BACKGROUND: For over two decades, the Nottingham Prognostic Index (NPI) has been used in the United Kingdom to calculate risk scores and inform management about breast cancer patients. It is derived using just three clinical variables - nodal involvement, tumour size and grade. New scientific methods now make cost-effective measurement of many biological characteristics of tumour tissue from breast cancer biopsy samples possible. However, the number of potential explanatory variables to be considered presents a statistical challenge. The aim of this study was to investigate whether in ER+ tamoxifen-treated breast cancer patients, biological variables can add value to NPI predictors, to provide improved prognostic stratification in terms of overall recurrence-free survival (RFS) and also in terms of remaining recurrence free while on tamoxifen treatment (RFoT). A particular goal was to enable the discrimination of patients with a very low risk of recurrence. METHODS: Tissue samples of 401 cases were analysed by microarray technology, providing biomarker data for 72 variables in total, from AKT, BAD, HER, MTOR, PgR, MAPK and RAS families. Only biomarkers screened as potentially informative (i.e., exhibiting univariate association with recurrence) were offered to the multivariate model. The multiple imputation method was used to deal with missing values, and bootstrap sampling was used to assess internal validity and refine the model. RESULTS: Neither the RFS nor RFoT models derived included Grade, but both had better predictive and discrimination ability than NPI. A slight difference was observed between models in terms of biomarkers included, and, in particular, the RFoT model alone included HER2. The estimated 7-year RFS rates in the lowest-risk groups by RFS and RFoT models were 95 and 97%, respectively, whereas the corresponding rate for the lowest-risk group of NPI was 89%. CONCLUSION: The findings demonstrate considerable potential for improved prognostic modelling by incorporation of biological variables into risk prediction. In particular, the ability to identify a low-risk group with minimal risk of recurrence is likely to have clinical appeal. With larger data sets and longer follow-up, this modelling approach has the potential to enhance an understanding of the interplay of biological characteristics, treatment and cancer recurrence. British Journal of Cancer (2010) 102, 1503 - 1510. doi:10.1038/sj.bjc.6605627 www.bjcancer.co

Effects of Dibutyryl Cyclic-AMP on Survival and Neuronal Differentiation of Neural Stem/Progenitor Cells Transplanted into Spinal Cord Injured Rats

Neural stem/progenitor cells (NSPCs) have great potential as a cell replacement therapy for spinal cord injury. However, poor control over transplant cell differentiation and survival remain major obstacles. In this study, we asked whether dibutyryl cyclic-AMP (dbcAMP), which was shown to induce up to 85% in vitro differentiation of NSPCs into neurons would enhance survival of transplanted NSPCs through prolonged exposure either in vitro or in vivo through the controlled release of dbcAMP encapsulated within poly(lactic-co-glycolic acid) (PLGA) microspheres and embedded within chitosan guidance channels. NSPCs, seeded in fibrin scaffolds within the channels, differentiated in vitro to betaIII-tubulin positive neurons by immunostaining and mRNA expression, in response to dbcAMP released from PLGA microspheres. After transplantation in spinal cord injured rats, the survival and differentiation of NSPCs was evaluated. Untreated NSPCs, NSPCs transplanted with dbcAMP-releasing microspheres, and NSPCs pre-differentiated with dbcAMP for 4 days in vitro were transplanted after rat spinal cord transection and assessed 2 and 6 weeks later. Interestingly, NSPC survival was highest in the dbcAMP pre-treated group, having approximately 80% survival at both time points, which is remarkable given that stem cell transplantation often results in less than 1% survival at similar times. Importantly, dbcAMP pre-treatment also resulted in the greatest number of in vivo NSPCs differentiated into neurons (37±4%), followed by dbcAMP-microsphere treated NSPCs (27±14%) and untreated NSPCs (15±7%). The reverse trend was observed for NSPC-derived oligodendrocytes and astrocytes, with these populations being highest in untreated NSPCs. This combination strategy of stem cell-loaded chitosan channels implanted in a fully transected spinal cord resulted in extensive axonal regeneration into the injury site, with improved functional recovery after 6 weeks in animals implanted with pre-differentiated stem cells in chitosan channels