Modeling the Effects of Water Treatment and Removal in Controlling Yellow Fever

In 1878, thousands in Memphis were killed during an outbreak of yellow fever, a viral hemorrhagic fever transmitted by the Aedes aegypti mosquito, which has affected regions including North and South America, Europe, Africa, and the Caribbean. This disease still affects individuals in Africa and Central and South America. We have developed a mathematical model consisting of nine ordinary differential equations which describe the dynamics of the human and mosquito populations during a yellow fever epidemic. Our model investigates the effects that treatment and removal of standing water have on a mosquito population and consequently a yellow fever epidemic. We have examined the stability of the disease-free equilibrium and the conditions under which the disease-free equilibrium is stable

Real-world disease-modifying therapy usage in persons with relapsing-remitting multiple sclerosis: Cross-sectional data from the Swiss Multiple Sclerosis Registry.

INTRODUCTION Several disease-modifying therapies (DMTs), covering a broad spectrum of mechanisms of action, have been approved by regulatory agencies for the treatment of relapsing-remitting multiple sclerosis (RRMS). However, only little is known about the current real-world treatment situation in Switzerland. Based on data from a diverse population of 668 persons with RRMS from the Swiss Multiple Sclerosis Registry (SMSR), the present study aims to fill this gap with a descriptive, cross-sectional approach. METHODS Data originated from the SMSR baseline questionnaire and follow-up surveys. Data on current health status and life situation in the last 6 months were extracted from the survey distributed throughout 2020 and 2021, while data on disease-modifying therapy (DMT) histories were included from preceding surveys. Initially, data was stratified into three DMT groups according to the current DMT status (NO (No DMT), CONTINUED (DMT started more than 6 months ago), and NEW (DMT started less than 6 months ago)). In a subsequent analysis, the sample was stratified into groups corresponding to the five most frequently prescribed DMTs. Self-reported outcomes including therapy discontinuation or interruption, relapses and side-effects in the last 6 months were analyzed per group. Life and health situation parameters were also determined and analyzed. RESULTS The study population consisted of 445 (66.6%) individuals belonging to the CONTINUED, 84 (12.6%) to the NEW, and 139 (20.8%) to the NO group. Within the NO group, 24 (17.3%) reported relapses. Furthermore, self-reported relapses (28 (33.3%)), side-effects (39 (46.4%)), and treatment discontinuations or interruptions (30 (35.7%)) occurred more frequently in the NEW compared to the CONTINUED group (37 (8.3%), 125 (28.1%), 8 (1.8%), respectively). The three groups also differed with respect to age, time since diagnosis, number of symptoms, DMT history, and health-related quality of life. The five most frequently prescribed DMTs included fingolimod (33.4%), dimethyl fumarate (25.0%), ocrelizumab (23.6%), natalizumab (10.6%) and teriflunomide (7.5%). The frequency of self-reported relapses ranged from 9.7% to 13.6%. Notable differences were found in the number of self-reported side-effects, ranging from 9.1% with natalizumab to 56.7% with dimethyl fumarate. DISCUSSION This cross-sectional analysis suggested that the majority of individuals with RRMS in Switzerland continuously receive tolerable DMT. However, groups not receiving DMT or struggling with side-effects or continued disease worsening while on DMT still persist. It is conceivable that the number of self-reported symptoms indicates the need for more detailed clarification of the DMT characteristics and expectations of treatment outcomes. Injectable DMTs no longer play a major role in the treatment of RRMS in Switzerland and a trend toward an early use of potent drugs is emerging

Peanut butter feeding induces oral tolerance in genetically diverse collaborative cross mice

BackgroundEarly dietary introduction of peanut has shown efficacy in clinical trials and driven pediatric recommendations for early introduction of peanut to children with heightened allergy risk worldwide. Unfortunately, tolerance is not induced in every case, and a subset of patients are allergic prior to introduction. Here we assess peanut allergic sensitization and oral tolerance in genetically diverse mouse strains.ObjectiveWe aimed to determine whether environmental adjuvant-driven airway sensitization and oral tolerance to peanut could be induced in various genetically diverse mouse strains.MethodsC57BL/6J and 12 Collaborative Cross (CC) mouse strains were fed regular chow or ad libitum peanut butter to induce tolerance. Tolerance was tested by attempting to sensitize mice via intratracheal exposure to peanut and lipopolysaccharide (LPS), followed by intraperitoneal peanut challenge. Peanut-specific immunoglobulins and peanut-induced anaphylaxis were assessed.ResultsWithout oral peanut feeding, most CC strains (11/12) and C57BL/6J induced peanut-specific IgE and IgG1 following airway exposure to peanut and LPS. With oral peanut feeding none of the CC strains nor C57BL/6J mice became sensitized to peanut or experienced anaphylaxis following peanut challenge.ConclusionAllergic sensitization and oral tolerance to peanut can be achieved across a range of genetically diverse mice. Notably, the same strains that became allergic via airway sensitization were tolerized by feeding high doses of peanut butter before sensitization, suggesting that the order and route of peanut exposure are critical for determining the allergic fate

Major depressive disorder subtypes and depression symptoms in multiple sclerosis: What is different compared to the general population?

OBJECTIVE To compare and characterize major depressive disorder (MDD) subtypes (i.e., pure atypical, pure melancholic and mixed atypical-melancholic) and depression symptoms in persons with multiple sclerosis (PwMS) with persons without MS (Pw/oMS) fulfilling the DSM-5 criteria for a past 12-month MDD. METHODS MDD in PwMS (n = 92) from the Swiss Multiple Sclerosis Registry was compared with Pw/oMS (n = 277) from a Swiss community-based study. Epidemiological MDD diagnoses were based on the Mini-SPIKE (shortened form of the Structured Psychopathological Interview and Rating of the Social Consequences for Epidemiology). Logistic and multinomial regression analyses (adjusted for sex, age, civil status, depression and severity) were computed for comparisons and characterization. Latent class analysis (LCA) was conducted to empirically identify depression subtypes in PwMS. RESULTS PwMS had a higher risk for the mixed atypical-melancholic MDD subtype (OR = 2.22, 95% CI = 1.03-4.80) compared to Pw/oMS. MDD in PwMS was specifically characterized by a higher risk of the two somatic atypical depression symptoms 'weight gain' (OR = 6.91, 95% CI = 2.20-21.70) and 'leaden paralysis' (OR = 3.03, 95% CI = 1.35-6.82) and the symptom 'irritable/angry' (OR = 3.18, 95% CI = 1.08-9.39). CONCLUSIONS MDD in PwMS was characterized by a higher risk for specific somatic atypical depression symptoms and the mixed atypical-melancholic MDD subtype. The pure atypical MDD subtype, however, did not differentiate between PwMS and Pw/oMS. Given the high phenomenological overlap with MS symptoms, the mixed atypical-melancholic MDD subtype represents a particular diagnostic challenge

The Real-World Experiences of Persons With Multiple Sclerosis During the First COVID-19 Lockdown: Application of Natural Language Processing.

The increasing availability of "real-world" data in the form of written text holds promise for deepening our understanding of societal and health-related challenges. Textual data constitute a rich source of information, allowing the capture of lived experiences through a broad range of different sources of information (eg, content and emotional tone). Interviews are the "gold standard" for gaining qualitative insights into individual experiences and perspectives. However, conducting interviews on a large scale is not always feasible, and standardized quantitative assessment suitable for large-scale application may miss important information. Surveys that include open-text assessments can combine the advantages of both methods and are well suited for the application of natural language processing (NLP) methods. While innovations in NLP have made large-scale text analysis more accessible, the analysis of real-world textual data is still complex and requires several consecutive steps. We developed and subsequently examined the utility and scientific value of an NLP pipeline for extracting real-world experiences from textual data to provide guidance for applied researchers. We applied the NLP pipeline to large-scale textual data collected by the Swiss Multiple Sclerosis (MS) registry. Such textual data constitute an ideal use case for the study of real-world text data. Specifically, we examined 639 text reports on the experienced impact of the first COVID-19 lockdown from the perspectives of persons with MS. The pipeline has been implemented in Python and complemented by analyses of the "Linguistic Inquiry and Word Count" software. It consists of the following 5 interconnected analysis steps: (1) text preprocessing; (2) sentiment analysis; (3) descriptive text analysis; (4) unsupervised learning-topic modeling; and (5) results interpretation and validation. A topic modeling analysis identified the following 4 distinct groups based on the topics participants were mainly concerned with: "contacts/communication;" "social environment;" "work;" and "errands/daily routines." Notably, the sentiment analysis revealed that the "contacts/communication" group was characterized by a pronounced negative emotional tone underlying the text reports. This observed heterogeneity in emotional tonality underlying the reported experiences of the first COVID-19-related lockdown is likely to reflect differences in emotional burden, individual circumstances, and ways of coping with the pandemic, which is in line with previous research on this matter. This study illustrates the timely and efficient applicability of an NLP pipeline and thereby serves as a precedent for applied researchers. Our study thereby contributes to both the dissemination of NLP techniques in applied health sciences and the identification of previously unknown experiences and burdens of persons with MS during the pandemic, which may be relevant for future treatment

Factors associated with time from first-symptoms to diagnosis and treatment initiation of Multiple Sclerosis in Switzerland.

Recent studies emphasise the importance of timely diagnosis and early initiation of disease-modifying treatment in the long-term prognosis of multiple sclerosis. The objective of this study was to investigate factors associated with extended time to diagnosis and time to disease-modifying treatment initiation in the Swiss Multiple Sclerosis Registry. We used retrospective data (diagnoses 1996-2017) of the survey-based Swiss Multiple Sclerosis Registry and fitted logistic regression models (extended time to diagnosis ≥2 years from first symptoms, extended time to disease-modifying treatment initiation ≥1 year from diagnosis) with demographic and a priori defined variables. Our study, based on 996 persons with multiple sclerosis, suggests that 40% had an extended time to diagnosis, and extended time to disease-modifying treatment initiation was seen in 23%. Factors associated with extended time to diagnosis were primary progressive multiple sclerosis (odds ratio (OR) 5.09 (3.12-8.49)), diagnosis setting outside of hospital (neurologist (private practice) OR 1.54 (1.16-2.05)) and more uncommon first symptoms (per additional symptom OR 1.17 (1.06-1.30)). Older age at onset (per additional 5 years OR 0.84 (0.78-0.90)) and gait problems (OR 0.65 (0.47-0.89)) or paresthesia (OR 0.72 (0.54-0.95)) as first symptoms were associated with shorter time to diagnosis. Extended time to disease-modifying treatment initiation was associated with older age at diagnosis (per additional 5 years OR 1.18 (1.09-1.29)). In more recent years, time to diagnosis and time to disease-modifying treatment initiation tended to be shorter. Even in recent periods, substantial and partially systematic variation regarding time to diagnosis and time to disease-modifying treatment initiation remains. With the emerging paradigm of early treatment, the residual variation should be monitored carefully

Tourism as connectedness.

Late modernity in developed nations is characterized by changing social and psychological conditions, including individualization, processes of competition and loneliness. Remaining socially connected is becoming increasingly important. In this situation, travel provides meaning through physical encounters, inclusion in traveller Gemeinschaft based on shared norms, beliefs and interests, and social status in societies increasingly defined by mobilities. As relationships are forged and found in mobility, travel is no longer an option, rather a necessity for sociality, identity construction, affirmation or alteration. Social contexts and the underlying motivations for tourism have changed fundamentally in late modernity: non-tourism has become a threat to self-conceptions. By integrating social and psychological perspectives, this paper expands and deepens existing travel and mobilities discussions to advance the understanding of tourism as a mechanism of social connectedness, and points to implications for future tourism research