Predicting dengue fever outbreaks in French Guiana using climate indicators

Background Dengue fever epidemic dynamics are driven by complex interactions between hosts, vectors and viruses. Associations between climate and dengue have been studied around the world, but the results have shown that the impact of the climate can vary widely from one study site to another. In French Guiana, climate-based models are not available to assist in developing an early warning system. This study aims to evaluate the potential of using oceanic and atmospheric conditions to help predict dengue fever outbreaks in French Guiana. Methodology/Principal Findings Lagged correlations and composite analyses were performed to identify the climatic conditions that characterized a typical epidemic year and to define the best indices for predicting dengue fever outbreaks during the period 1991-2013. A logistic regression was then performed to build a forecast model. We demonstrate that a model based on summer Equatorial Pacific Ocean sea surface temperatures and Azores High sea-level pressure had predictive value and was able to predict 80% of the outbreaks while incorrectly predicting only 15% of the non-epidemic years. Predictions for 2014-2015 were consistent with the observed non-epidemic conditions, and an outbreak in early 2016 was predicted. Conclusions/Significance These findings indicate that outbreak resurgence can be modeled using a simple combination of climate indicators. This might be useful for anticipating public health actions to mitigate the effects of major outbreaks, particularly in areas where resources are limited and medical infrastructures are generally insufficient

Exploring the endocannabinoidome in genetically obese (ob/ob) and diabetic (db/db) mice: Links with inflammation and gut microbiota

Background: Obesity and type 2 diabetes are two interrelated metabolic disorders characterized by insulin resistance and a mild chronic inflammatory state. We previously observed that leptin (ob/ob) and leptin receptor (db/db) knockout mice display a distinct inflammatory tone in the liver and adipose tissue. The present study aimed at investigating whether alterations in these tissues of the molecules belonging to the endocannabinoidome (eCBome), an extension of the endocannabinoid (eCB) signaling system, whose functions are important in the context of metabolic disorders and inflammation, could reflect their different inflammatory phenotypes. Results: The basal eCBome lipid and gene expression profiles, measured by targeted lipidomics and qPCR transcriptomics, respectively, in the liver and subcutaneous or visceral adipose tissues, highlighted a differentially altered eCBome tone, which may explain the impaired hepatic function and more pronounced liver inflammation remarked in the ob/ob mice, as well as the more pronounced inflammatory state observed in the subcutaneous adipose tissue of db/db mice. In particular, the levels of linoleic acid-derived endocannabinoid-like molecules, of one of their 12-lipoxygenase metabolites and of Trpv2 expression, were always altered in tissues exhibiting the highest inflammation. Correlation studies suggested the possible interactions with some gut microbiota bacterial taxa, whose respective absolute abundances were significantly different between ob/ob and the db/db mice. Conclusions: The present findings emphasize the possibility that bioactive lipids and the respective receptors and enzymes belonging to the eCBome may sustain the tissue-dependent inflammatory state that characterizes obesity and diabetes, possibly in relation with gut microbiome alterations

A Many-body Problem with Point Interactions on Two Dimensional Manifolds

A non-perturbative renormalization of a many-body problem, where non-relativistic bosons living on a two dimensional Riemannian manifold interact with each other via the two-body Dirac delta potential, is given by the help of the heat kernel defined on the manifold. After this renormalization procedure, the resolvent becomes a well-defined operator expressed in terms of an operator (called principal operator) which includes all the information about the spectrum. Then, the ground state energy is found in the mean field approximation and we prove that it grows exponentially with the number of bosons. The renormalization group equation (or Callan-Symanzik equation) for the principal operator of the model is derived and the $\beta$ function is exactly calculated for the general case, which includes all particle numbers.Comment: 28 pages; typos are corrected, three figures are adde

The use of telemedicine with frail elderly patients in the Netherlands - experience of caregivers in an outpatient setting

The use of telemedicine (telephone and video consultations) has increased over the past decades and has grown substantially during the COVID-19 pandemic. Multimorbidity, visual - and hearing impairment, cognitive impairment and lack of technical skills might complicate the use of telemedicine in frail elderly patients. Limited research on this topic is has been performed. The aim of this article is to investigate which elements of care could be performed by telemedicine and what patient characteristics are useful in selecting patients for telemedicine. To get more information about the use of telemedicine in frail elderly patients, an online survey was conducted amongst caregivers working in geriatric outpatient care departments in the Netherlands. 67 caregivers completed the survey. The results indicate there is limited experience in video consultations in this population. The experience so far is mainly positive. Caregivers indicate the following elements of care could be performed by telemedicine: follow-up consultations, taking an (hetero)anamnesis, medication review, conversations with multiple contacts or caregivers and informing about test results. Our advice is to decide in dialogue with patient and caregiver, which form of consultation is feasible, desirable and appropriate for every individual process and consultation

The opposite of Dante's hell? The transfer of ideas for social housing at international congresses in the 1850s–1860s

With the advent of industrialization, the question of developing adequate housing for the emergent working classes became more pressing than before. Moreover, the problem of unhygienic houses in industrial cities did not stop at the borders of a particular nation-state; sometimes literally as pandemic diseases spread out 'transnationally'. It is not a coincidence that in the nineteenth century the number of international congresses on hygiene and social topics expanded substantially. However, the historiography about social policy in general and social housing in particular, has often focused on individual cases because of the different pace of industrial and urban development and is thus dominated by national perspectives. In this paper, I elaborate on transnational exchange processes and local adaptations and transformations. I focus on the transfer of the housing model of SOMCO in Mulhouse, (a French house building association) during social international congresses. I examine whether cross-national networking enabled and facilitated the implementation of ideas on the local scale. I will elaborate on the transmission and the local adaptation of the Mulhouse-model in Belgium. Convergences, divergences, and different factors that influenced the local transformations (personal choice, political situation, socioeconomic circumstances) will be taken into accoun

Phase II study of olaparib in patients with refractory Ewing sarcoma following failure of standard chemotherapy

Background: Preclinical studies have documented antitumor activity of PARP inhibition both in vitro and in vivo, against Ewing sarcoma cells. This study aimed to translate that observation into a clinical trial to assess the efficacy and tolerability of olaparib, a PARP inhibitor, in patients with advanced Ewing sarcoma (EWS) progressing after prior chemotherapy. Methods: In this nonrandomized phase II trial, adult participants with radiographically measureable metastatic EWS received olaparib tablets, 400 mg orally twice daily, until disease progression or drug intolerance. Tumor measurements were determined by CT or MRI at 6 and 12 weeks after starting olaparib administration, and then every 8 weeks thereafter. Tumor response determinations were made according to RECIST 1.1, and adverse event determinations were made according to CTCAE, version 4.0. A total of 22 participants were planned to be enrolled using a conventional 2-step phase II study design. If no objective responses were observed after 12 participants had been followed for at least 3 months, further accrual would be stopped. Results: 12 participants were enrolled, and all were evaluable. There were no objective responses (PR/CR), 4 SD (duration 10.9, 11.4, 11.9, and 17.9 wks), and 8 PD as best response. Of the SD, 2 had minor responses (−9% and −11.7% by RECIST 1.1). The median time to disease progression was 5.7 weeks. Further enrollment was therefore discontinued. No significant or unexpected toxicities were observed with olaparib, with only a single case each of grade 3 anemia and grade 3 thrombocytopenia observed. Conclusions: This study is the first report of a prospective phase II trial to evaluate the safety and efficacy of a PARP inhibitor in patients with advanced Ewing sarcoma after failure of standard chemotherapy. Olaparib administration was safe and well tolerated when administered to this small heavily pre-treated cohort at the 400 mg BID dose, although the median duration of dosing was for only 5.7 weeks. No significant responses or durable disease control was seen, and the short average interval to disease progression underscores the aggressiveness of this disease. Other studies to combine cytotoxic chemotherapy with PARP inhibition in EWS are actively ongoing. Trial registration ClinicalTrials.gov Identifier: NCT0158354

Induced pseudoscalar coupling of the proton weak interaction

The induced pseudoscalar coupling $g_p$ is the least well known of the weak coupling constants of the proton's charged--current interaction. Its size is dictated by chiral symmetry arguments, and its measurement represents an important test of quantum chromodynamics at low energies. During the past decade a large body of new data relevant to the coupling $g_p$ has been accumulated. This data includes measurements of radiative and non radiative muon capture on targets ranging from hydrogen and few--nucleon systems to complex nuclei. Herein the authors review the theoretical underpinnings of $g_p$, the experimental studies of $g_p$, and the procedures and uncertainties in extracting the coupling from data. Current puzzles are highlighted and future opportunities are discussed.Comment: 58 pages, Latex, Revtex4, prepared for Reviews of Modern Physic

Dendritic cells loaded with killed breast cancer cells induce differentiation of tumor-specific cytotoxic T lymphocytes

BACKGROUND: Early clinical trials, mostly in the setting of melanoma, have shown that dendritic cells (DCs) expressing tumor antigens induce some immune responses and some clinical responses. A major difficulty is the extension to other tumors, such as breast carcinoma, for which few defined tumor-associated antigens are available. We have demonstrated, using both prostate carcinoma and melanoma as model systems, that DCs loaded with killed allogeneic tumor cell lines can induce CD8(+ )T cells to differentiate into cytotoxic T lymphocytes (CTLs) specific for shared tumor antigens. METHODS: The present study was designed to determine whether DCs would capture killed breast cancer cells and present their antigens to autologous CD4(+ )and CD8(+ )T cells. RESULTS: We show that killed breast cancer cells are captured by immature DCs that, after induced maturation, can efficiently present MHC class I and class II peptides to CD8(+ )and CD4(+ )T lymphocytes. The elicited CTLs are able to kill the target cells without a need for pretreatment with interferon gamma. CTLs can be obtained by culturing the DCs loaded with killed breast cancer cells with unseparated peripheral blood lymphocytes, indicating that the DCs can overcome any potential inhibitory effects of breast cancer cells. CONCLUSION: Loading DCs with killed breast cancer cells may be considered a novel approach to breast cancer immunotherapy and to identification of shared breast cancer antigens