Shining Light on Modifications of Gravity

Many modifications of gravity introduce new scalar degrees of freedom, and in such theories matter fields typically couple to an effective metric that depends on both the true metric of spacetime and on the scalar field and its derivatives. Scalar field contributions to the effective metric can be classified as conformal and disformal. Disformal terms introduce gradient couplings between scalar fields and the energy momentum tensor of other matter fields, and cannot be constrained by fifth force experiments because the effects of these terms are trivial around static non-relativistic sources. The use of high-precision, low-energy photon experiments to search for conformally coupled scalar fields, called axion-like particles, is well known. In this article we show that these experiments are also constraining for disformal scalar field theories, and are particularly important because of the difficulty of constraining these couplings with other laboratory experiments.Comment: 20 pages, 10 figures. v2: Matches version accepted by JCAP; additional discussion of the strong coupling scale. Conclusions unchange

The pupil near response is short lasting and intact in virtual reality head mounted displays

The pupil of the eye constricts when moving focus from an object further away to an object closer by. This is called the pupil near response, which typically occurs together with accommodation and vergence responses. When immersed in virtual reality mediated through a head-mounted display, this triad is disrupted by the vergence-accommodation conflict. However, it is not yet clear if the disruption also affects the pupil near response. Two experiments were performed to assess this. The first experiment had participants follow a target that first appeared at a far position and then moved to either a near position (far-to-near; FN) or to another far position (far-to-far; FF). The second experiment had participants follow a target that jumped between five positions, which was repeated at several distances. Experiment 1 showed a greater pupil constriction amplitude for FN trials, compared to FF trials, suggesting that the pupil near response is intact in head-mounted display mediated virtual reality. Experiment 2 did not find that average pupil dilation differed when fixating targets at different distances, suggesting that the pupil near response is transient and does not result in sustained pupil size changes

Malnutrition is associated with dynamic physical performance

Background Malnutrition and poor physical performance are both conditions that increase in prevalence with age; however, their interrelation in a clinically relevant population has not been thoroughly studied. Aims This study aimed to determine the strength of the association between malnutrition and measures of both static and dynamic physical performance in a cohort of geriatric outpatients. Methods This cross-sectional study included 286 older adults (mean age 81.8, SD 7.2 years, and 40.6% male) who were referred to geriatric outpatient mobility clinics. The presence of malnutrition was determined using the Short Nutritional Assessment Questionnaire (SNAQ, cut-off ≥ 2 points). Measures of dynamic physical performance included timed up and go (TUG), 4-m walk test, and chair stand test (CST). Static performance encompassed balance tests and hand grip strength (HGS). Physical performance was standardized into sex-specific Z-scores. The association between malnutrition and each individual measure of physical performance was assessed using linear regression analysis. Results 19.9% of the cohort was identified as malnourished. Malnutrition was most strongly associated with CST and gait speed; less strong but significant associations were found between malnutrition and TUG. There was no significant association between malnutrition and HGS or balance. Discussion Physical performance was associated with malnutrition, specifically, dynamic rather than static measures. This may reflect muscle power being more impacted by nutritional status than muscle strength; however, this needs to be further addressed. Conclusions Malnutrition is associated with dynamic physical performance in geriatric outpatients, which should inform diagnosis and treatment/prevention strategies

Feasibility study of ultrasound-guided resection of tongue cancer with immediate specimen examination to improve margin control - Comparison with conventional treatment

Objectives: Squamous cell carcinoma of the tongue (SCCT) is preferably treated by surgery. Free resection margins (&gt; 5 mm) provide local control and disease-free survival. However, close (1-5 mm) and positive margins (&lt; 1 mm) are frequently encountered. We present our first experience of in-vivo ultrasound (US) guided SCCT resections followed by ex-vivo US control on the resection specimen to obtain free margins. We compare the results with those from a hisorical cohort of 91 conventionally treated SCCT patients. Materials and methods: Ten patients with SCCT were included in a consecutive US-cohort. We aimed for a 5-10 mm margin during surgery, while we visualized the resection plane on US. Ex-vivo US measurements on the resection specimen determined whether there was any need for an immediate re-resection. US measurements were then compared with histopathology. Histopathological margins were compared with a consecutive cohort of 91 patients who had undergone conventional surgery for a SCCT. Results: In the US cohort, 70% of the margins were free. In the conventional cohort, this figure was 17% (P = 0.005). US predicted minimal histopathological margin distance with a mean +/- SD error of 1.9 +/- 1.8 mm. The mean +/- SD of the histopathological overall submucosal/deep margin distance was 7.9 +/- 2.1 mm in the US cohort and 7.0 +/- 2.2 mm in the conventional cohort (P = 0.188). Ex-vivo examination through use of US indicated an immediate re-resection, which prevented local adjuvant treatment. Conclusion: Use of US-guided SCCT resection is feasible and improves margin control.</p

Feasibility study of ultrasound-guided resection of tongue cancer with immediate specimen examination to improve margin control - Comparison with conventional treatment

Objectives: Squamous cell carcinoma of the tongue (SCCT) is preferably treated by surgery. Free resection margins (> 5 mm) provide local control and disease-free survival. However, close (1-5 mm) and positive margins (< 1 mm) are frequently encountered. We present our first experience of in-vivo ultrasound (US) guided SCCT resections followed by ex-vivo US control on the resection specimen to obtain free margins. We compare the results with those from a hisorical cohort of 91 conventionally treated SCCT patients. Materials and methods: Ten patients with SCCT were included in a consecutive US-cohort. We aimed for a 5-10 mm margin during surgery, while we visualized the resection plane on US. Ex-vivo US measurements on the resection specimen determined whether there was any need for an immediate re-resection. US measurements were then compared with histopathology. Histopathological margins were compared with a consecutive cohort of 91 patients who had undergone conventional surgery for a SCCT. Results: In the US cohort, 70% of the margins were free. In the conventional cohort, this figure was 17% (P = 0.005). US predicted minimal histopathological margin distance with a mean +/- SD error of 1.9 +/- 1.8 mm. The mean +/- SD of the histopathological overall submucosal/deep margin distance was 7.9 +/- 2.1 mm in the US cohort and 7.0 +/- 2.2 mm in the conventional cohort (P = 0.188). Ex-vivo examination through use of US indicated an immediate re-resection, which prevented local adjuvant treatment. Conclusion: Use of US-guided SCCT resection is feasible and improves margin control

Sperm DNA damage causes genomic instability in early embryonic development

Genomic instability is common in human embryos, but the underlying causes are largely unknown. Here, we examined the consequences of sperm DNA damage on the embryonic genome by single-cell whole-genome sequencing of individual blastomeres from bovine embryos produced with sperm damaged by γ-radiation. Sperm DNA damage primarily leads to fragmentation of the paternal chromosomes followed by random distribution of the chromosomal fragments over the two sister cells in the first cell division. An unexpected secondary effect of sperm DNA damage is the induction of direct unequal cleavages, which include the poorly understood heterogoneic cell divisions. As a result, chaotic mosaicism is common in embryos derived from fertilizations with damaged sperm. The mosaic aneuploidies, uniparental disomies, and de novo structural variation induced by sperm DNA damage may compromise fertility and lead to rare congenital disorders when embryos escape developmental arrest

The pupil near response is short lasting and intact in virtual reality head mounted displays

The pupil of the eye constricts when moving focus from an object further away to an object closer by. This is called the pupil near response, which typically occurs together with accommodation and vergence responses. When immersed in virtual reality mediated through a head-mounted display, this triad is disrupted by the vergence-accommodation conflict. However, it is not yet clear if the disruption also affects the pupil near response. Two experiments were performed to assess this. The first experiment had participants follow a target that first appeared at a far position and then moved to either a near position (far-to-near; FN) or to another far position (far-to-far; FF). The second experiment had participants follow a target that jumped between five positions, which was repeated at several distances. Experiment 1 showed a greater pupil constriction amplitude for FN trials, compared to FF trials, suggesting that the pupil near response is intact in head-mounted display mediated virtual reality

Colistin resistance mutations in phoQ can sensitize Klebsiella pneumoniae to IgM-mediated complement killing

International audienceAbstract Due to multi-drug resistance, physicians increasingly use the last-resort antibiotic colistin to treat infections with the Gram-negative bacterium Klebsiella pneumoniae. Unfortunately, K. pneumoniae can also develop colistin resistance. Interestingly, colistin resistance has dual effects on bacterial clearance by the immune system. While it increases resistance to antimicrobial peptides, colistin resistance has been reported to sensitize certain bacteria for killing by human serum. Here we investigate the mechanisms underlying this increased serum sensitivity, focusing on human complement which kills Gram-negatives via membrane attack complex (MAC) pores. Using in vitro evolved colistin resistant strains and a fluorescent MAC-mediated permeabilization assay, we showed that two of the three tested colistin resistant strains, Kp209_CSTR and Kp257_CSTR, were sensitized to MAC. Transcriptomic and mechanistic analyses focusing on Kp209_CSTR revealed that a mutation in the phoQ gene locked PhoQ in an active state, making Kp209_CSTR colistin resistant and MAC sensitive. Detailed immunological assays showed that complement activation on Kp209_CSTR in human serum required specific IgM antibodies that bound Kp209_CSTR but did not recognize the wild-type strain. Together, our results show that developing colistin resistance affected recognition of Kp209_CSTR and its killing by the immune system

Outcomes and risk score for distal pancreatectomy with celiac axis resection (DP-CAR) : an international multicenter analysis

Background: Distal pancreatectomy with celiac axis resection (DP-CAR) is a treatment option for selected patients with pancreatic cancer involving the celiac axis. A recent multicenter European study reported a 90-day mortality rate of 16%, highlighting the importance of patient selection. The authors constructed a risk score to predict 90-day mortality and assessed oncologic outcomes. Methods: This multicenter retrospective cohort study investigated patients undergoing DP-CAR at 20 European centers from 12 countries (model design 2000-2016) and three very-high-volume international centers in the United States and Japan (model validation 2004-2017). The area under receiver operator curve (AUC) and calibration plots were used for validation of the 90-day mortality risk model. Secondary outcomes included resection margin status, adjuvant therapy, and survival. Results: For 191 DP-CAR patients, the 90-day mortality rate was 5.5% (95 confidence interval [CI], 2.2-11%) at 5 high-volume (1 DP-CAR/year) and 18% (95 CI, 9-30%) at 18 low-volume DP-CAR centers (P=0.015). A risk score with age, sex, body mass index (BMI), American Society of Anesthesiologists (ASA) score, multivisceral resection, open versus minimally invasive surgery, and low- versus high-volume center performed well in both the design and validation cohorts (AUC, 0.79 vs 0.74; P=0.642). For 174 patients with pancreatic ductal adenocarcinoma, the R0 resection rate was 60%, neoadjuvant and adjuvant therapies were applied for respectively 69% and 67% of the patients, and the median overall survival period was 19months (95 CI, 15-25months). Conclusions: When performed for selected patients at high-volume centers, DP-CAR is associated with acceptable 90-day mortality and overall survival. The authors propose a 90-day mortality risk score to improve patient selection and outcomes, with DP-CAR volume as the dominant predictor

Individual patient data meta-analysis of diagnostic and prognostic studies in obstetrics, gynaecology and reproductive medicine

BACKGROUND: In clinical practice a diagnosis is based on a combination of clinical history, physical examination and additional diagnostic tests. At present, studies on diagnostic research often report the accuracy of tests without taking into account the information already known from history and examination. Due to this lack of information, together with variations in design and quality of studies, conventional meta-analyses based on these studies will not show the accuracy of the tests in real practice. By using individual patient data (IPD) to perform meta-analyses, the accuracy of tests can be assessed in relation to other patient characteristics and allows the development or evaluation of diagnostic algorithms for individual patients. In this study we will examine these potential benefits in four clinical diagnostic problems in the field of gynaecology, obstetrics and reproductive medicine. METHODS/DESIGN: Based on earlier systematic reviews for each of the four clinical problems, studies are considered for inclusion. The first authors of the included studies will be invited to participate and share their original data. After assessment of validity and completeness the acquired datasets are merged. Based on these data, a series of analyses will be performed, including a systematic comparison of the results of the IPD meta-analysis with those of a conventional meta-analysis, development of multivariable models for clinical history alone and for the combination of history, physical examination and relevant diagnostic tests and development of clinical prediction rules for the individual patients. These will be made accessible for clinicians. DISCUSSION: The use of IPD meta-analysis will allow evaluating accuracy of diagnostic tests in relation to other relevant information. Ultimately, this could increase the efficiency of the diagnostic work-up, e.g. by reducing the need for invasive tests and/or improving the accuracy of the diagnostic workup. This study will assess whether these benefits of IPD meta-analysis over conventional meta-analysis can be exploited and will provide a framework for future IPD meta-analyses in diagnostic and prognostic research