Eradication-resolution dynamics with stochastic flare-ups

In infectious disease as well as in cancer, the ultimate outcome of the curative response, mediated by the body itself or through drug treatment, is either successful eradication or a resurgence of the disease (“flare-up” or “relapse”), depending on random fluctuations that dominate the dynamics of the system when the number of diseased cells has become very low. The presence of a low-numbers bottle-neck in the dynamics, which is unavoidable if eradication is to take place at all, renders at least one phase of the dynamics essentially stochastic. However, the eradicating agents (e.g. immune cells, drug molecules) generally remain at high numbers during the critical bottle-neck phase, sufficiently so to warrant a deterministic treatment. This leads us to consider a hybrid stochastic-deterministic approach where the infected cells are treated stochastically whereas the eradicating agents are treated deterministically. Exploiting the fact that the number of eradicating agents typically decreases monotonically during the resolution phase of the response, we derive a set of coupled first-order differential equations that describe the probability of ultimate eradication as a function of the system's state, and we consider a number of biomedical applications

How a tariff-based trade policy affects domestic prices, import volumes and welfare: an empirical analysis of the eu´s retaliatory tariffs on the Us

This Project examines how the retaliatory tariffs imposed by the EU in response to the US steel and aluminum tariffs affect EU prices and welfare over the period from June 2018 to May 2020. Using a partial equilibrium model that assumes perfect competition, the graphical analysis and the regression show that the prices of the goods subject to the tariffs are fully passed on to EU producers and consumers, suggesting that they bear the full burden of the tariff increase. Consequently, the EU suffers a deadweight welfare lossof almost€144 million over the two years considered

Composting at Sarah Lawrence College

Our proposal describes two economically viable and efficient methods of reducing the amount of pre and post-consumer waste produced by the Sarah Lawrence community. Bates dining facility, the largest on-campus dining facility, produces roughly 35 lbs. of organic food waste every day. However, the installation of an easy-to-use composting mechanism, such as the A500 Rocket composter or the Ridan manual composter (both of which are distributed by NATH Sustainability Solutions), and/or the implementation of a larger-scale vermicomposting program, would divert at least 50% of Sarah Lawrence’s organic waste material from reaching landfills, lower campus-wide trash removal and fertilizer costs, and promote sustainability initiatives within the Sarah Lawrence community and surrounding community.https://digitalcommons.slc.edu/undergrad_sustainproject/1005/thumbnail.jp

Loss‐of‐function mutations in the <i>ALPL </i>gene presenting with adult onset osteoporosis and low serum concentrations of total alkaline phosphatase

Hypophosphatasia (HPP) is a rare inherited disorder characterized by rickets and low circulating concentrations of total alkaline phosphatase (ALP) caused by mutations in ALPL. Severe HPP presents in childhood but milder forms can present in adulthood. The prevalence and clinical features of adult HPP are poorly defined. The aim of this study was to evaluate the prevalence and clinical significance of low serum total alkaline phosphatase (ALP) levels in a clinic‐based population of adult osteoporotic patients. We searched for patients with low ALP in a cohort of 3285 patients referred to an osteoporosis clinic over a 10‐year period and performed mutation screening of ALPL in those with low ALP (≤40 U/L) on two or more occasions. These individuals were matched with four clinic controls with a normal ALP. We also evaluated the prevalence of low ALP and ALPL mutations in 639 individuals from the general population from the same region. We identified 16/3285 (0.49%) clinic patients with low ALP and 14 (87.5%) had potentially pathogenic variants in ALPL. Eight of these individuals were heterozygous for mutations previously described in HPP and 2 were heterozygous for novel mutations (p.Arg301Trp and p.Tyr101X). These mutations were not found in clinic controls or in the general population. Eight patients with low ALP, including 4 with ALPL mutations, were treated with bisphosphonates for an average of 6.5 years. In these individuals, the rate of fractures during treatment was comparable to that in normal ALP clinic controls who were treated with bisphosphonates. We conclude that heterozygous loss‐of‐function mutations in ALPL are common in osteoporosis patients with low ALP. Further studies are required to determine how best these individuals should be treated. © 2019 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research

A Sustainable Campus for the Future: Proposals for Sarah Lawrence College

The combined version of A Sustainable Campus for the Future: Proposals for Sarah Lawrence College comes from a joint project between the students in Economics of the Ecological Crisis and Global Change Biology in Spring 2016, taught by Nicholas Reksten and Michelle Hersh, respectively.https://digitalcommons.slc.edu/undergrad_sustainproject/1009/thumbnail.jp

Multi-armed bandit models for 2D grasp planning with uncertainty

Abstract — For applications such as warehouse order fulfill-ment, robot grasps must be robust to uncertainty arising from sensing, mechanics, and control. One way to achieve robustness is to evaluate the performance of candidate grasps by sampling perturbations in shape, pose, and gripper approach and to com-pute the probability of force closure for each candidate to iden-tify a grasp with the highest expected quality. Since evaluating the quality of each grasp is computationally demanding, prior work has turned to cloud computing. To improve computational efficiency and to extend this work, we consider how Multi-Armed Bandit (MAB) models for optimizing decisions can be applied in this context. We formulate robust grasp planning as a MAB problem and evaluate convergence times towards an optimal grasp candidate using 100 object shapes from the Brown Vision 2D Lab Dataset with 1000 grasp candidates per object. We consider the case where shape uncertainty is represented as a Gaussian process implicit surface (GPIS) with Gaussian uncertainty in pose, gripper approach angle, and coefficient of friction. We find that Thompson Sampling and the Gittins index MAB methods converged to within 3 % of the optimal grasp up to 10x faster than uniform allocation and 5x faster than iterative pruning. I

Auditory training changes temporal lobe connectivity in Wernicke's aphasia: a randomised trial

Introduction Aphasia is one of the most disabling sequelae after stroke, occurring in 25%–40% of stroke survivors. However, there remains a lack of good evidence for the efficacy or mechanisms of speech comprehension rehabilitation. Trial Design This within-subjects trial tested two concurrent interventions in 20 patients with chronic aphasia with speech comprehension impairment following left hemisphere stroke: (1) phonological training using ‘Earobics’ software and (2) a pharmacological intervention using donepezil, an acetylcholinesterase inhibitor. Donepezil was tested in a double-blind, placebo-controlled, cross-over design using block randomisation with bias minimisation. Methods The primary outcome measure was speech comprehension score on the comprehensive aphasia test. Magnetoencephalography (MEG) with an established index of auditory perception, the mismatch negativity response, tested whether the therapies altered effective connectivity at the lower (primary) or higher (secondary) level of the auditory network. Results Phonological training improved speech comprehension abilities and was particularly effective for patients with severe deficits. No major adverse effects of donepezil were observed, but it had an unpredicted negative effect on speech comprehension. The MEG analysis demonstrated that phonological training increased synaptic gain in the left superior temporal gyrus (STG). Patients with more severe speech comprehension impairments also showed strengthening of bidirectional connections between the left and right STG. Conclusions Phonological training resulted in a small but significant improvement in speech comprehension, whereas donepezil had a negative effect. The connectivity results indicated that training reshaped higher order phonological representations in the left STG and (in more severe patients) induced stronger interhemispheric transfer of information between higher levels of auditory cortex

"It's what midwifery is all about": Western Australian midwives' experiences of being 'with woman' during labour and birth in the known midwife model

Background: The phenomenon of being 'with woman' is fundamental to midwifery as it underpins its philosophy, relationships and practices. There is an identified gap in knowledge around the 'with woman' phenomenon from the perspective of midwives providing care in a variety of contexts. As such, the aim of this study was to explore the experiences of being 'with woman' during labour and birth from the perspective of midwives' working in a model where care is provided by a known midwife. Methods: A descriptive phenomenological design was employed with ten midwives working in a 'known midwife' model who described their experiences of being 'with woman' during labour and birth. The method was informed by Husserlian philosophy which seeks to explore the same phenomenon through rich descriptions by individuals revealing commonalities of the experience. Results: Five themes emerged 1) Building relationships; 2) Woman centred care; 3) Impact on the midwife; 4) Impact on the woman; and 5) Challenges in the Known Midwife model. Midwives emphasised the importance of trusting relationships while being 'with woman', confirming that this relationship extends beyond the woman - midwife relationship to include the woman's support people and family. Being 'with woman' during labour and birth in the context of the relationship facilitates woman-centred care. Being 'with woman' influences midwives, and, it is noted, the women that midwives are working with. Finally, challenges that impact being 'with woman' in the known midwife model are shared by midwives. Conclusions: Findings offer valuable insight into midwives' experiences of being 'with woman' in the context of models that provide care by a known midwife. In this model, the trusting relationship is the conduit for being 'with woman' which influences the midwife, the profession of midwifery, as well as women and their families. Descriptions of challenges to being 'with woman' provide opportunities for professional development and service review. Rich descriptions from the unique voice of midwives, provided insight into the applied practices of being 'with woman' in a known midwife model which adds important knowledge concerning a phenomenon so deeply embedded in the philosophy and practices of the profession of midwifery

Diabetes Is Associated with Cerebrovascular but not Alzheimer\u27s Disease Neuropathology

INTRODUCTION: The relationship of diabetes to specific neuropathologic causes of dementia is incompletely understood. METHODS: We used logistic regression to evaluate the association between diabetes and infarcts, Braak neurofibrillary tangle stage, and neuritic plaque score in 2365 autopsied persons. In a subset of \u3e1300 persons with available cognitive data, we examined the association between diabetes and cognition using Poisson regression. RESULTS: Diabetes increased odds of brain infarcts (odds ratio [OR] = 1.57, P \u3c .0001), specifically lacunes (OR = 1.71, P \u3c .0001), but not Alzheimer\u27s disease neuropathology. Diabetes plus infarcts was associated with lower cognitive scores at end of life than infarcts or diabetes alone, and diabetes plus high level of Alzheimer\u27s neuropathologic changes was associated with lower mini-mental state examination scores than the pathology alone. DISCUSSION: This study supports the conclusions that diabetes increases the risk of cerebrovascular but not Alzheimer\u27s disease pathology, and at least some of diabetes\u27 relationship to cognitive impairment may be modified by neuropathology

A highly polymorphic effector protein promotes fungal virulence through suppression of plant-associated Actinobacteria

Plant pathogens secrete effector proteins to support host colonization through a wide range of molecular mechanisms, while plant immune systems evolved receptors to recognize effectors or their activities to mount immune responses to halt pathogens. Importantly, plants do not act as single organisms, but rather as holobionts that actively shape their microbiota as a determinant of health. The soil-borne fungal pathogen Verticillium dahliae was recently demonstrated to exploit the VdAve1 effector to manipulate the host microbiota to promote vascular wilt disease in the absence of the corresponding immune receptor Ve1. We identify a multiallelic V. dahliae gene displaying c. 65% sequence similarity to VdAve1, named VdAve1-like (VdAve1L), which shows extreme sequence variation, including alleles that encode dysfunctional proteins, indicative of selection pressure to overcome host recognition. We show that the orphan cell surface receptor Ve2, encoded at the Ve locus, does not recognize VdAve1L. Additionally, we demonstrate that the full-length variant VdAve1L2 possesses antimicrobial activity, like VdAve1, yet with a divergent activity spectrum, that is exploited by V. dahliae to mediate tomato colonization through the direct suppression of antagonistic Actinobacteria in the host microbiota. Our findings open up strategies for more targeted biocontrol against microbial plant pathogens