Identification of Heavy Metal Contaminants in the Upper Clark Fork River Basin Using Laser Induced Spectroscopy and Hyperspectral Spectroscopy

The Upper Clark Fork River Basin is home to many current and abandoned mining sites which contribute to the presence of heavy metals. Heavy metals on surface sediments can harm human and ecological health, so it is important to identify these contaminants for removal. Laser Induced Breakdown Spectroscopy (LIBS) is an active spectroscopy method because it uses a laser pulse to remove a small amount of mass through laser ablation. As the electrons return to their ground states, the unique spectral signatures and intensity can determine the percentage of the element in the sample. Hyperspectral Spectroscopy (HS) is a passive method that uses natural light reflected from the sample to determine the range and concentration of the wavelength emitted. The resulting plot compares reflectance versus wavelength. HS can be applied to an airborne survey

Effect of clinical isolate or cleavage site mutations in the SARS-CoV-2 spike protein on protein stability, cleavage, and cell–cell fusion

The trimeric severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein (S) is the sole viral protein responsible for both viral binding to a host cell and the membrane fusion event needed for cell entry. In addition to facilitating fusion needed for viral entry, S can also drive cell-cell fusion, a pathogenic effect observed in the lungs of SARS-CoV-2-infected patients. While several studies have investigated S requirements involved in viral particle entry, examination of S stability and factors involved in S cell-cell fusion remain limited. A furin cleavage site at the border between the S1 and S2 subunits (S1/S2) has been identified, along with putative cathepsin L and transmembrane serine protease 2 cleavage sites within S2. We demonstrate that S must be processed at the S1/S2 border in order to mediate cell-cell fusion and that mutations at potential cleavage sites within the S2 subunit alter S processing at the S1/S2 border, thus preventing cell-cell fusion. We also identify residues within the internal fusion peptide and the cytoplasmic tail that modulate S-mediated cell-cell fusion. In addition, we examined S stability and protein cleavage kinetics in a variety of mammalian cell lines, including a bat cell line related to the likely reservoir species for SARS-CoV-2, and provide evidence that proteolytic processing alters the stability of the S trimer. This work therefore offers insight into S stability, proteolytic processing, and factors that mediate S cell-cell fusion, all of which help give a more comprehensive understanding of this high-profile therapeutic target

Hypercalcemic Crisis Caused by a Parathyroid Mass Requiring Thoracoscopic Resection

Objective: To describe the presentation, work up, and treatment of a giant parathyroid adenoma presenting as hypercalcemic crisis that ultimately weighed 57 g and extended into the mediastinum, requiring hand-assisted thoracoscopic resection. Methods: The patient is a 68-year-old man with a prior history of parathyroidectomy, who initially presented with a severe hypercalcemia of 16.3 mg/dL and a parathyroid hormone (PTH) level of 2692 pg/mL on routine labs. Results: Diagnostic and staging work up revealed a 7.2-cm mass extending from just superior to the sternal notch into the right posterior mediastinum to the carina, causing esophageal displacement. No evidence of local invasion or distant metastasis was observed on further imaging, and cytology demonstrated hypercellular parathyroid tissue. The PTH level of the aspirate was >5000 pg/mL. The patient subsequently underwent a right hand-assisted video-assisted thoracoscopic resection of the intrathoracic mass. Final pathology identified a 7.0-cm, 57-g parathyroid adenoma, without any pathologic findings suspicious for malignancy. However, the endocrine surgery team plans for annual laboratory assessment to ensure no recurrence. Conclusion: Primary hyperparathyroidism is most commonly caused by a single adenoma. However, in the setting of severe hypercalcemia and elevated PTH, one must have a high suspicion for malignancy, and care should be taken to remove the mass en bloc. For extremely large adenomas extending into the mediastinum, a minimally invasive, hand-assisted, thoracoscopic approach is a safe and effective method of resection

Assessment of lymphatic filariasis prior to re-starting mass drug administration campaigns in coastal Kenya.

BACKGROUND: Lymphatic filariasis (LF) is a debilitating disease associated with extensive disfigurement and is one of a diverse group of diseases referred to as neglected tropical diseases (NTDs) which mainly occur among the poorest populations. In line with global recommendations to eliminate LF, Kenya launched its LF elimination programme in 2002 with the aim to implement annual mass drug administration (MDA) in order to interrupt LF transmission. However, the programme faced financial and administrative challenges over the years such that sustained annual MDA was not possible. Recently, there has been renewed interest to eliminate LF and the Kenyan Ministry of Health, through support from World Health Organization (WHO), restarted annual MDA in 2015. The objective of this study was to evaluate the current status of LF infection in the endemic coastal region of Kenya before MDA campaigns were restarted. RESULTS: Ten sentinel sites in Kwale, Kilifi, Tana River, Lamu, and Taita-Taveta counties in coastal Kenya were selected for participation in a cross-sectional survey of LF infection prevalence. At least 300 individuals in each sentinel village were sampled through random house-to-house visits. During the day, the point-of-care immunochromatographic test (ICT) was used to detect the presence of Wuchereria bancrofti circulating filarial antigen in finger prick blood samples collected from residents of the selected sentinel villages. Those individuals who tested positive with the ICT test were requested to provide a night-time blood sample for microfilariae (MF) examination. The overall prevalence of filarial antigenaemia was 1.3% (95% CI: 0.9-1.8%). Ndau Island in Lamu County had the highest prevalence (6.3%; 95% CI: 4.1-9.7%), whereas sites in Kilifi and Kwale counties had prevalences?<?1.7%. Mean microfilarial density was also higher in Ndau Island (234 MF/ml) compared to sentinel sites in Kwale and Kilifi counties (< 25 MF/ml). No LF infection was detected in Tana River and Taita-Taveta counties. Overall, more than 88% of the study participants reported to have used a bed net the previous night. CONCLUSIONS: Prevalence of LF infection is generally very low in coastal Kenya, but there remain areas that require further rounds of MDA if the disease is to be eliminated as a public health problem in line with the ongoing global elimination efforts. However, areas where there was no evidence of LF transmission should be considered for WHO-recommended transmission assessment surveys in view of stopping MDA

Beliefs About Cancer and Diet among Those Considering Genetic Testing for Colon Cancer

To assess beliefs about the role of diet in cancer prevention among individuals considering genetic testing for Lynch Syndrome

Prevalence of ultrasound-determined cystic endometrial hyperplasia and the relationship with age in dogs

To investigate the potential relationship between age and diagnosis of cystic endometrial hyperplasia (CEH) in the bitches, 348 ultrasound examinations from 240 bitches (Labradors, Golden Retrievers, German Shepherds, Flat Coated Retrievers, or crosses of those breeds aged between 1.6 and 7.2 years at examination) were examined. A subpopulation of 32 bitches that had completed their breeding careers at 6 years or more of age was also identified. Of all, 18.3% of the bitches were diagnosed with CEH; these cases were newly diagnosed when bitches were between 2.5 years and 7.3 years of age. The proportion of ultrasound examinations in which CEH was identified increased from 6.8% of examinations on 2-year-old breeding bitches to 60.0% of examinations on 6-year-old bitches. Logistic regression identified a positive correlation between mean age at the examination and presence of CEH (χ2 = 30.74, degrees of freedom = 1, P < 0.001). For 32 bitches that had completed their breeding career, the prevalence of CEH was 56.3%, age at the diagnosis ranged from 3.8 to 7.3 years, and the proportion of bitches affected with CEH increased from 6.3% at 3 years of age to 56.3% at 7 years of age. These data support the contention that the prevalence of CEH increases with age

Predicting the Availability of Hematopoietic Stem Cell Donors Using Machine Learning

Hematopoietic stem cell transplantation (HSCT) is firmly established as an important curative therapy for patients with hematologic malignancies and other blood disorders. Apart from finding HLA-matched donors during the HSCT process, donor availability remains a key consideration as the time taken from diagnosis to transplant is recognized to adversely affect patient outcome. In this study, we aimed to develop and validate a machine learning approach to predict the availability of stem cell donors. We retrospectively collected a data set containing 10,258 verification typing requests made during the HSCT process in the British Bone Marrow Registry (BBMR) between January 1, 2013, and December 31, 2018. Three machine learning algorithms were implemented and compared, including boosted decision trees (BDTs), logistic regression, and support vector machines. Area under the receiver operating characteristic curve (AUC) was primarily used to assess the algorithms. The experimental results showed that BDTs performed better in predicting the availability of BBMR donors. The overall predictive power of the model, using AUC on the test cohort of 2052 records, was found to be 0.826. Our findings show that machine learning can predict the availability of donors with a high degree of accuracy. We propose the use of the BDT machine learning approach to predict the availability of BBMR donors and use the predictive scores during the HSCT process to ensure patients with blood cancers or disorders receive a transplant at the optimum time

Understanding Heterogeneity in the Impact of National Neglected Tropical Disease Control Programmes: Evidence from School-Based Deworming in Kenya.

BACKGROUND: The implementation of soil-transmitted helminth (STH) treatment programmes occurs in varied environmental, social and economic contexts. Programme impact will be influenced by factors that affect the reduction in the prevalence and intensity of infections following treatment, as well as the subsequent rate of reinfection. To better understand the heterogeneity of programme impact and its underlying reasons, we investigated the influence of contextual factors on reduction in STH infection as part of the national school based deworming (SBD) programme in Kenya. MATERIALS AND METHODS: Data on the prevalence and intensity of infection were collected within the monitoring and evaluation component of the SBD programme at baseline and after delivery of two annual treatment rounds in 153 schools in western Kenya. Using a framework that considers STH epidemiology and transmission dynamics, capacity to deliver treatment, operational feasibility and financial capacity, data were assembled at both school and district (county) levels. Geographic heterogeneity of programme impact was assessed by descriptive and spatial analyses. Factors associated with absolute reductions of Ascaris lumbricoides and hookworm infection prevalence and intensity were identified using mixed effects linear regression modelling adjusting for baseline infection levels. PRINCIPAL FINDINGS: The reduction in prevalence and intensity of A. lumbricoides and hookworms varied significantly by county and within counties by school. Multivariable analysis of factors associated with programme impact showed that absolute A. lumbricoides reductions varied by environmental conditions and access to improved sanitation at schools or within the community. Larger reduction in prevalence and intensity of hookworms were found in schools located within areas with higher community level access to improved sanitation and within counties with higher economic and health service delivery indicator scores. CONCLUSIONS: The study identifies factors associated with the impact of school-based deworming and in particular highlights how access to water, sanitation and hygiene and environmental conditions influence the impact of deworming programmes

Immunotherapy with CD25/CD71-allodepleted T cells to improve T-cell reconstitution after matched unrelated donor hematopoietic stem cell transplant: a randomized trial

BACKGROUND AND AIMS: Delayed immune reconstitution is a major challenge after matched unrelated donor (MUD) stem cell transplant (SCT). In this randomized phase 2 multi-center trial, Adoptive Immunotherapy with CD25/71 allodepleted donor T cells to improve immunity after unrelated donor stem cell transplant (NCT01827579), the authors tested whether allodepleted donor T cells (ADTs) can safely be used to improve immune reconstitution after alemtuzumab-based MUD SCT for hematological malignancies. METHODS: Patients received standard of care or up to three escalating doses of ADTs generated through CD25+/CD71+ immunomagnetic depletion. The primary endpoint of the study was circulating CD3+ T-cell count at 4 months post-SCT. Twenty-one patients were treated, 13 in the ADT arm and eight in the control arm. RESULTS: The authors observed a trend toward improved CD3+ T-cell count at 4 months in the ADT arm versus the control arm (230/µL versus 145/µL, P = 0.18), and three ADT patients achieved normal CD3+ T-cell count at 4 months (>700/µL). The rates of significant graft-versus-host disease (GVHD) were comparable in both cohorts, with grade ≥2 acute GVHD in seven of 13 and four of eight patients and chronic GVHD in three of 13 and three of eight patients in the ADT and control arms, respectively. CONCLUSIONS: These data suggest that adoptive transfer of ADTs is safe, but that in the MUD setting the benefit in terms of T-cell reconstitution is limited. This approach may be of more use in the context of more rigorous T-cell depletion