In December 2013, the first locally-acquired chikungunya virus (CHIKV) infections in the Americas were reported in the Caribbean. As of May 16, 55,992 cases had been reported and the outbreak was ...still spreading. Identification of newly affected locations is paramount to intervention activities, but challenging due to limitations of current data on the outbreak and on CHIKV transmission. We developed models to make probabilistic predictions of spread based on current data considering these limitations.
Branching process models capturing travel patterns, local infection prevalence, climate dependent transmission factors, and associated uncertainty estimates were developed to predict probable locations for the arrival of CHIKV-infected travelers and for the initiation of local transmission. Many international cities and areas close to where transmission has already occurred were likely to have received infected travelers. Of the ten locations predicted to be the most likely locations for introduced CHIKV transmission in the first four months of the outbreak, eight had reported local cases by the end of April. Eight additional locations were likely to have had introduction leading to local transmission in April, but with substantial uncertainty.
Branching process models can characterize the risk of CHIKV introduction and spread during the ongoing outbreak. Local transmission of CHIKV is currently likely in several Caribbean locations and possible, though uncertain, for other locations in the continental United States, Central America, and South America. This modeling framework may also be useful for other outbreaks where the risk of pathogen spread over heterogeneous transportation networks must be rapidly assessed on the basis of limited information.
Dysregulated hematopoiesis occurs in several chronic inflammatory diseases, but it remains unclear how hematopoietic stem cells (HSCs) in the bone marrow (BM) sense peripheral inflammation and ...contribute to tissue damage in arthritis. Here, we show the HSC gene expression program is biased toward myelopoiesis and differentiation skewed toward granulocyte-monocyte progenitors (GMP) during joint and intestinal inflammation in experimental spondyloarthritis (SpA). GM-CSF-receptor is increased on HSCs and multipotent progenitors, favoring a striking increase in myelopoiesis at the earliest hematopoietic stages. GMP accumulate in the BM in SpA and, unexpectedly, at extramedullary sites: in the inflamed joints and spleen. Furthermore, we show that GM-CSF promotes extramedullary myelopoiesis, tissue-toxic neutrophil accumulation in target organs, and GM-CSF prophylactic or therapeutic blockade substantially decreases SpA severity. Surprisingly, besides CD4
T cells and innate lymphoid cells, mast cells are a source of GM-CSF in this model, and its pathogenic production is promoted by the alarmin IL-33.
Atypical teratoid rhabdoid tumor (ATRT) of the CNS is a highly malignant neoplasm primarily affecting young children, with a historic median survival ranging from 6 to 11 months. Based on a previous ...pilot series, a prospective multi-institutional trial was conducted for patients with newly diagnosed CNS ATRT.
Treatment was divided into five phases: preirradiation, chemoradiation, consolidation, maintenance, and continuation therapy. Intrathecal chemotherapy was administered, alternating intralumbar and intraventricular routes. Radiation therapy (RT) was prescribed, either focal (54 Gy) or craniospinal (36 Gy, plus primary boost), depending on age and extent of disease at diagnosis.
Between 2004 and 2006, 25 patients were enrolled; 20 were eligible for evaluation. Median age at diagnosis was 26 months (range, 2.4 months to 19.5 years). Gross total resection of the primary tumor was achieved in 11 patients. Fourteen patients had M0 disease at diagnosis, one patient had M2 disease, and five patients had M3 disease. Fifteen patients received radiation therapy: 11 focal and four craniospinal. Significant toxicities, in addition to the expected, included radiation recall (n = 2) and transverse myelitis (n = 1). There was one toxic death. Of the 12 patients who were assessable for chemotherapeutic response (pre-RT), the objective response rate was 58%. The objective response rate observed after RT was 38%. The 2-year progression-free and overall survival rates are 53% +/- 13% and 70% +/- 10%, respectively. Median overall survival has not yet been reached.
This intensive multimodality regimen has resulted in a significant improvement in time to progression and overall survival for patients with this previously poor-prognosis tumor.
Background. The Middle East respiratory syndrome coronavirus (MERS-CoV) was discovered September 2012 in the Kingdom of Saudi Arabia (KSA). The first US case of MERS-CoV was confirmed on 2 May 2014. ...Methods. We summarize the clinical symptoms and signs, laboratory and radiologic findings, and MERS-CoV–specific tests. Results. The patient is a 65-year-old physician who worked in a hospital in KSA where MERS-CoV patients were treated. His illness onset included malaise, myalgias, and low-grade fever. He flew to the United States on day of illness (DOI) 7. His first respiratory symptom, a dry cough, developed on DOI 10. On DOI 11, he presented to an Indiana hospital as dyspneic, hypoxic, and with a right lower lobe infiltrate on chest radiography. On DOI 12, his serum tested positive by real-time reverse transcription polymerase chain reaction (rRT-PCR) for MERS-CoV and showed high MERS-CoV antibody titers, whereas his nasopharyngeal swab was rRT-PCR negative. Expectorated sputum was rRT-PCR positive the following day, with a high viral load (5.31 × 106 copies/mL). He was treated with antibiotics, intravenous immunoglobulin, and oxygen by nasal cannula. He was discharged on DOI 22. The genome sequence was similar (>99%) to other known MERS-CoV sequences, clustering with those from KSA from June to July 2013. Conclusions. This patient had a prolonged nonspecific prodromal illness before developing respiratory symptoms. Both sera and sputum were rRT-PCR positive when nasopharyngeal specimens were negative. US clinicians must be vigilant for MERS-CoV in patients with febrile and/or respiratory illness with recent travel to the Arabian Peninsula, especially among healthcare workers.
Although comprehensive school-based physical activity interventions are efficacious when tested under research conditions, they often require adaptation in order for implementation at scale. This ...paper reports the effectiveness of an adapted efficacious school-based intervention in improving children’s moderate to vigorous physical activity. The impact of strategies to support program implementation was also assessed.
A cluster RCT of low socioeconomic elementary schools in New South Wales, Australia.
Consenting schools were randomized (25 intervention, 21 control) using a computerized random number function. Follow-up measures were taken at 6 months post-randomization (May–August 2015) by blinded research assistants. The multicomponent school-based intervention, based on an efficacious school-based physical activity program (Supporting Children’s Outcomes using Rewards, Exercise and Skills), consisted of four physical activity strategies and seven implementation support strategies. The intervention was adapted for scalability and delivery by a local health service over 6 months. The primary outcome was accelerometer assessed, student mean daily minutes spent in moderate to vigorous physical activity. Physical education lesson quality and other school physical activity practices were also assessed.
Participants (n=1,139, 49% male) were third- through sixth-grade students at follow-up (May–August 2015). Valid wear time and analysis of data were provided for 989 (86%) participants (571 intervention, 568 control). At 6-month follow-up, there were no significant effects in overall daily minutes of moderate to vigorous physical activity between groups (1.96 minutes, 95% CI= –3.49, 7.41, p=0.48). However, adjusted difference in mean minutes of overall vigorous physical activity (2.19, 95% CI=0.06, 4.32, p=0.04); mean minutes of school day moderate to vigorous physical activity (2.90, 95% CI=0.06, 5.85, p=0.05); and mean minutes of school day vigorous physical activity (1.81, 95% CI=0.78, 2.83, p≤0.01) were significantly different in favor of the intervention group. Physical education lesson quality and school physical activity practices were significantly different favoring the intervention group (analyzed October 2015–January 2016).
The modified intervention was not effective in increasing children’s overall daily minutes of moderate to vigorous physical activity, when adapted for implementation at scale. However, the intervention did improve daily minutes of vigorous physical activity and school day moderate to vigorous physical activity, lesson quality, and school physical activity practices.
Australian New Zealand Clinical Trials Registry: ACTRN12615000437561.
Public health travel restrictions (PHTR) are crucial measures during communicable disease outbreaks to prevent transmission during commercial airline travel and mitigate cross-border importation and ...spread. We evaluated PHTR implementation for US citizens on the Diamond Princess during its coronavirus disease (COVID-19) outbreak in Japan in February 2020 to explore how PHTR reduced importation of COVID-19 to the United States during the early phase of disease containment. Using PHTR required substantial collaboration among the US Centers for Disease Control and Prevention, other US government agencies, the cruise line, and public health authorities in Japan. Original US PHTR removal criteria were modified to reflect international testing protocols and enable removal of PHTR for persons who recovered from illness. The impact of PHTR on epidemic trajectory depends on the risk for transmission during travel and geographic spread of disease. Lessons learned from the Diamond Princess outbreak provide critical information for future PHTR use.
Protist plankton can be divided into three main groups: phytoplankton, zooplankton, and mixoplankton. In situ methods for studying phytoplankton and zooplankton are relatively straightforward since ...they generally target chlorophyll/photosynthesis or grazing activity, while the integration of both processes within a single cell makes mixoplankton inherently challenging to study. As a result, we understand less about mixoplankton physiology and their role in food webs, biogeochemical cycling, and ecosystems compared to phytoplankton and zooplankton. In this paper, we posit that by merging conventional techniques, such as microscopy and physiological data, with innovative methods like in situ single-cell sorting and omics datasets, in conjunction with a diverse array of modeling approaches ranging from single-cell modeling to comprehensive Earth system models, we can propel mixoplankton research into the forefront of aquatic ecology. We present eight crucial research questions pertaining to mixoplankton and mixotrophy, and briefly outline a combination of existing methods and models that can be used to address each question. Our intent is to encourage more interdisciplinary research on mixoplankton, thereby expanding the scope of data acquisition and knowledge accumulation for this understudied yet critical component of aquatic ecosystems.
Background. On 8 October 2008, members of a tour group experienced diarrhea and vomiting throughout an airplane flight from Boston, Massachusetts, to Los Angeles, California, resulting in an ...emergency diversion 3 h after takeoff. An investigation was conducted to determine the cause of the outbreak, assess whether transmission occurred on the airplane, and describe risk factors for transmission. Methods. Passengers and crew were contacted to obtain information about demographics, symptoms, locations on the airplane, and possible risk factors for transmission. Case patients were defined as passengers with vomiting or diarrhea (⩾ loose stools in 24 h) and were asked to submit stool samples for norovirus testing by real-time reverse-transcription polymerase chain reaction. Results. Thirty-six (88%) of 41 tour group members were interviewed, and 15 (41%) met the case definition (peak date of illness onset, 8 October 2008). Of 106 passengers who were not tour group members, 85 (80%) were interviewed, and 7 (8%) met the case definition after the flight (peak date of illness onset, 10 October 2008). Multivariate logistic regression analysis showed that sitting in an aisle seat (adjusted relative risk, 11.0; 95% confidence interval, 1.4–84.9) and sitting near any tour group member (adjusted relative risk, 7.5; 95% confidence interval, 1.7–33.6) were associated with the development of illness. Norovirus genotype II was detected by reversetranscription polymerase chain reaction in stool samples from case patients in both groups. Conclusions. Despite the short duration, transmission of norovirus likely occurred during the flight.
Despite limited evidence regarding their utility, infrared thermal detection systems (ITDS) are increasingly being used for mass fever detection. We compared temperature measurements for 3 ITDS (FLIR ...ThermoVision A20M FLIR Systems Inc., Boston, MA, USA, OptoTherm Thermoscreen OptoTherm Thermal Imaging Systems and Infrared Cameras Inc., Sewickley, PA, USA, and Wahl Fever Alert Imager HSI2000S Wahl Instruments Inc., Asheville, NC, USA) with oral temperatures (≥ 100 °F = confirmed fever) and self-reported fever. Of 2,873 patients enrolled, 476 (16.6%) reported a fever, and 64 (2.2%) had a confirmed fever. Self-reported fever had a sensitivity of 75.0%, specificity 84.7%, and positive predictive value 10.1%. At optimal cutoff values for detecting fever, temperature measurements by OptoTherm and FLIR had greater sensitivity (91.0% and 90.0%, respectively) and specificity (86.0% and 80.0%, respectively) than did self-reports. Correlations between ITDS and oral temperatures were similar for OptoTherm (ρ = 0.43) and FLIR (ρ = 0.42) but significantly lower for Wahl (ρ = 0.14; p < 0.001). When compared with oral temperatures, 2 systems (OptoTherm and FLIR) were reasonably accurate for detecting fever and predicted fever better than self-reports.
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