Disease Knowledge Transfer across Neurodegenerative Diseases

We introduce Disease Knowledge Transfer (DKT), a novel technique for transferring biomarker information between related neurodegenerative diseases. DKT infers robust multimodal biomarker trajectories in rare neurodegenerative diseases even when only limited, unimodal data is available, by transferring information from larger multimodal datasets from common neurodegenerative diseases. DKT is a joint-disease generative model of biomarker progressions, which exploits biomarker relationships that are shared across diseases. Our proposed method allows, for the first time, the estimation of plausible, multimodal biomarker trajectories in Posterior Cortical Atrophy (PCA), a rare neurodegenerative disease where only unimodal MRI data is available. For this we train DKT on a combined dataset containing subjects with two distinct diseases and sizes of data available: 1) a larger, multimodal typical AD (tAD) dataset from the TADPOLE Challenge, and 2) a smaller unimodal Posterior Cortical Atrophy (PCA) dataset from the Dementia Research Centre (DRC), for which only a limited number of Magnetic Resonance Imaging (MRI) scans are available. Although validation is challenging due to lack of data in PCA, we validate DKT on synthetic data and two patient datasets (TADPOLE and PCA cohorts), showing it can estimate the ground truth parameters in the simulation and predict unseen biomarkers on the two patient datasets. While we demonstrated DKT on Alzheimer's variants, we note DKT is generalisable to other forms of related neurodegenerative diseases. Source code for DKT is available online: https://github.com/mrazvan22/dkt.Comment: accepted at MICCAI 2019, 13 pages, 5 figures, 2 table

Anatomic segmentectomy for stage I non–small-cell lung cancer: Comparison of video-assisted thoracic surgery versus open approach

ObjectivesAnatomic segmentectomy is increasingly being considered as a means of achieving an R0 resection for peripheral, small, stage I non–small-cell lung cancer. In the current study, we compare the results of video-assisted thoracic surgery (n = 104) versus open (n = 121) segmentectomy in the treatment of stage I non–small-cell lung cancer.MethodsA total of 225 consecutive anatomic segmentectomies were performed for stage IA (n = 138) or IB (n = 87) non–small-cell lung cancer from 2002 to 2007. Primary outcome variables included hospital course, complications, mortality, recurrence, and survival. Statistical comparisons were performed utilizing the t test and Fisher exact test. The probability of overall and recurrence-free survival was estimated with the Kaplan-Meier method, with significance being estimated by the log-rank test.ResultsMean age (69.9 years) and gender distribution were similar between the video-assisted thoracic surgery and open groups. Average tumor size was 2.3 cm (2.1 cm video-assisted thoracic surgery; 2.4 cm open). Mean follow-up was 16.2 (video-assisted thoracic surgery) and 28.2 (open) months. There were 2 perioperative deaths (2/225; 0.9%), both in the open group. Video-assisted thoracic surgery segmentectomy was associated with decreased length of stay (5 vs 7 days, P < .001) and pulmonary complications (15.4% vs 29.8%, P = .012) compared with open segmentectomy. Overall mortality, complications, local and systemic recurrence, and survival were similar between video-assisted thoracic surgery and open segmentectomy groups.ConclusionsVideo-assisted thoracic surgery segmentectomy can be performed with acceptable morbidity, mortality, recurrence, and survival. The video-assisted thoracic surgery approach affords a shorter length of stay and fewer postoperative pulmonary complications compared with open techniques. The potential benefits and limitations of segmentectomy will need to be further evaluated by prospective, randomized trials

Moving from information and collaboration to action: report from the 3rd International Dog Health Workshop, Paris in April 2017

Abstract Background Breed-related health problems in dogs have received increased focus over the last decade. Responsibility for causing and/or solving these problems has been variously directed towards dog breeders and kennel clubs, the veterinary profession, welfare scientists, owners, regulators, insurance companies and the media. In reality, all these stakeholders are likely to share some responsibility and optimal progress on resolving these challenges requires all key stakeholders to work together. The International Partnership for Dogs (IPFD), together with an alternating host organization, holds biennial meetings called the International Dog Health Workshops (IDHW). The Société Centrale Canine (French Kennel Club) hosted the 3rd IDHW, in Paris, in April, 2017. These meetings bring together a wide range of stakeholders in dog health, science and welfare to improve international sharing of information and resources, to provide a forum for ongoing collaboration, and to identify specific needs and actions to improve health, well-being and welfare in dogs. Results The workshop included 140 participants from 23 countries and was structured around six important issues facing those who work to improve dog health. These included individualized breed-specific strategies for health and breeding, extreme conformations, education and communication in relation to antimicrobial resistance, behavior and welfare, genetic testing and population-based evidence. A number of exciting actions were agreed during the meeting. These included setting up working groups to create tools to help breed clubs accelerate the implementation of breed-health strategies, review aspects of extreme conformation and share useful information on behavior. The meeting also heralded the development of an online resource of relevant information describing quality measures for DNA testing. A demand for more and better data and evidence was a recurring message stressed across all themes. Conclusions The meeting confirmed the benefits from inclusion of a diverse range of stakeholders who all play relevant and collaborative parts to improve future canine health. Firm actions were set for progress towards improving breed-related welfare. The next international workshop will be in the UK in 2019 and will be organized by the UK Kennel Club

Repurposing rapid diagnostic tests to detect falsified vaccines in supply chains

Substandard (including degraded) and falsified (SF) vaccines are a relatively neglected issue with serious global implications for public health. This has been highlighted during the rapid and widespread rollout of COVID-19 vaccines. There has been increasing interest in devices to screen for SF non-vaccine medicines including tablets and capsules to empower inspectors and standardise surveillance. However, there has been very limited published research focussed on repurposing or developing new devices for screening for SF vaccines. To our knowledge, rapid diagnostic tests (RDTs) have not been used for this purpose but have important potential for detecting falsified vaccines. We performed a proof-in-principle study to investigate their diagnostic accuracy using a diverse range of RDT-vaccine/falsified vaccine surrogate pairs. In an initial assessment, we demonstrated the utility of four RDTs in detecting seven vaccines. Subsequently, the four RDTs were evaluated by three blinded assessors with seven vaccines and four falsified vaccines surrogates. The results provide preliminary data that RDTs could be used by multiple international organisations, national medicines regulators and vaccine manufacturers/distributors to screen for falsified vaccines in supply chains, aligned with the WHO global ‘Prevent, Detect and Respond’ strategy

Wired for Her Face? Male Attentional Bias for Female Faces

Under conditions of inattention or deficits in orienting attention, special classes of stimuli (e.g. faces, bodies) are more likely to be perceived than other stimuli. This suggests that biologically salient visual stimuli automatically recruit attention, even when they are task-irrelevant or ignored. Here we report results from a behavioral experiment with female and male subjects and two magnetoencephalography (MEG) experiments with male subjects only, in which we investigated attentional capture with face and hand stimuli. In both the behavioral and MEG experiments, subjects were required to count the number of gender-specific targets from either face or hand categories within a block of stimuli. In the behavioral experiment, we found that male subjects were significantly more accurate in response to female than male face target blocks. There was no corresponding effect found in response to hand target blocks. Female subjects did not show a gender-based difference in response to face or hand target blocks. MEG results indicated that the male subjects’ responses to face stimuli in primary visual cortex (V1) and the face-selective part of the fusiform gyrus (FG) were reduced when male face stimuli were not relevant to the task, whereas female faces maintained a strong response in these areas in both task-relevant and task-irrelevant conditions. These results suggest that within the male brain, female face stimuli are more resilient to suppression than male faces, once attention is drawn to the part of the visual field where the face appears

Essential Role of Chromatin Remodeling Protein Bptf in Early Mouse Embryos and Embryonic Stem Cells

We have characterized the biological functions of the chromatin remodeling protein Bptf (Bromodomain PHD-finger Transcription Factor), the largest subunit of NURF (Nucleosome Remodeling Factor) in a mammal. Bptf mutants manifest growth defects at the post-implantation stage and are reabsorbed by E8.5. Histological analyses of lineage markers show that Bptf−/− embryos implant but fail to establish a functional distal visceral endoderm. Microarray analysis at early stages of differentiation has identified Bptf-dependent gene targets including homeobox transcriptions factors and genes essential for the development of ectoderm, mesoderm, and both definitive and visceral endoderm. Differentiation of Bptf−/− embryonic stem cell lines into embryoid bodies revealed its requirement for development of mesoderm, endoderm, and ectoderm tissue lineages, and uncovered many genes whose activation or repression are Bptf-dependent. We also provide functional and physical links between the Bptf-containing NURF complex and the Smad transcription factors. These results suggest that Bptf may co-regulate some gene targets of this pathway, which is essential for establishment of the visceral endoderm. We conclude that Bptf likely regulates genes and signaling pathways essential for the development of key tissues of the early mouse embryo

Primordial power spectrum from WMAP

The observed angular power spectrum of the cosmic microwave background temperature anisotropy, $C_l$, is a convolution of a cosmological radiative transport kernel with an assumed primordial power spectrum of inhomogeneities. Exquisite measurements of $C_l$ over a wide range of multipoles from the Wilkinson Microwave Anisotropy Probe (WMAP) has opened up the possibility to deconvolve the primordial power spectrum for a given set of cosmological parameters (base model). We implement an improved (error sensitive) Richardson-Lucy deconvolution algorithm on the measured angular power spectrum from WMAP assuming a concordance cosmological model. The most prominent feature of the recovered $P(k)$ is a sharp, infra-red cut off on the horizon scale. The resultant $C_l$ spectrum using the recovered spectrum has a likelihood far better than a scale invariant, or, `best fit' scale free spectra ($\Delta\ln{\cal L}=25$ {\it w.r.t.} Harrison Zeldovich, and, $\Delta\ln{\cal L}=11$ {\it w.r.t.} power law with $n_s=0.95$). The recovered $P(k)$ has a localized excess just below the cut-off which leads to great improvement of likelihood over the simple monotonic forms of model infra-red cut-off spectra considered in the post WMAP literature. The recovered $P(k)$, in particular, the form of infra-red cut-off is robust to small changes in the cosmological parameters. We show that remarkably similar form of infra-red cutoff is known to arise in very reasonable extensions and refinements of the predictions from simple inflationary scenarios. Our method can be extended to other cosmological observations such as the measured matter power spectrum and, in particular, the much awaited polarization spectrum from WMAP.Comment: 20 pages, 12 figures, uses Revtex4, Matches version accepted to Phys. Rev. D. More extensive discussion of the method in the appendix, references added and typos correcte

Beliefs and perceptions about the causes of breast cancer: a case-control study

Background: Attributions of causality are common for many diseases, including breast cancer. The risk of developing breast cancer can be reduced by modifications to lifestyle and behaviours to minimise exposure to specific risk factors, such as obesity. However, these modifications will only occur if women believe that certain behaviours/lifestyle factors have an impact on the development of breast cancer. Method: The Breast Cancer, Environment and Employment Study is a case-control study of breast cancer conducted in Western Australia between 2009 and 2011. As part of the study 1109 women with breast cancer and 1633 women without the disease completed a Risk Perception questionnaire in which they were asked in an open-ended question for specific cause/s to the development of breast cancer in themselves or in others. The study identified specific causal beliefs, and assessed differences in the beliefs between women with and without breast cancer. Results: The most common attributions in women without breast cancer were to familial or inherited factors (77.6%), followed by lifestyle factors, such as poor diet and smoking (47.1%), and environmental factors, such as food additives (45.4%). The most common attributions in women with breast cancer were to mental or emotional factors (46.3%), especially stress, followed by lifestyle factors (38.6%) and physiological factors (37.5%), particularly relating to hormonal history.Conclusions: While the majority of participants in this study provided one or more causal attributions for breast cancer, many of the reported risk factors do not correspond to those generally accepted by the scientific community. These misperceptions could be having a significant impact on the success of prevention and early detection programs that seek to minimise the pain and suffering caused by this disease. In particular, women who have no family history of the disease may not work to minimise their exposure to the modifiable risk factors