Cost-effectiveness of expanded latent TB infection testing and treatment: Lynn City, Massachusetts, USA.

BACKGROUND: Between October 2016 and March 2019, Lynn Community Health Center in Massachusetts implemented a targeted latent TB infection testing and treatment (TTT) program, increasing testing from a baseline of 1,200 patients tested to an average of 3,531 patients tested, or 9% of the population per year.METHODS: We compared pre-implementation TTT, represented by the first two quarters of implementation data, to TTT, represented by 12 quarters of data. Time, diagnostic, and laboratory resources were estimated using micro-costing. Other cost and testing data were obtained from the electronic health record, pharmaceutical claims, and published reimbursement rates. A Markov cohort model estimated future health outcomes and cost-effectiveness from a societal perspective in 2020 US dollars. Monte Carlo simulation generated 95% uncertainty intervals.RESULTS: The TTT program exhibited extended dominance over baseline pre-intervention testing and had an incremental cost-effectiveness ratio (ICER) of US$52,603 (US$22,008â-"US$95,360). When compared to baseline pre-TTT testing, the TTT program averted an estimated additional 7.12 TB cases, 3.49 hospitalizations, and 0.16 deaths per lifetime cohort each year.CONCLUSIONS: TTT was more cost-effective than baseline pre-implementation testing. Lynn Community Health Centerâ-™s experience can help inform other clinics considering expanding latent TB infection testing.

Detecting Intra-Field Variation in Rice Yield With Unmanned Aerial Vehicle Imagery and Deep Learning.

Unmanned aerial vehicles (UAVs) equipped with multispectral sensors offer high spatial and temporal resolution imagery for monitoring crop stress at early stages of development. Analysis of UAV-derived data with advanced machine learning models could improve real-time management in agricultural systems, but guidance for this integration is currently limited. Here we compare two deep learning-based strategies for early warning detection of crop stress, using multitemporal imagery throughout the growing season to predict field-scale yield in irrigated rice in eastern Arkansas. Both deep learning strategies showed improvements upon traditional statistical learning approaches including linear regression and gradient boosted decision trees. First, we explicitly accounted for variation across developmental stages using a 3D convolutional neural network (CNN) architecture that captures both spatial and temporal dimensions of UAV images from multiple time points throughout one growing season. 3D-CNNs achieved low prediction error on the test set, with a Root Mean Squared Error (RMSE) of 8.8% of the mean yield. For the second strategy, a 2D-CNN, we considered only spatial relationships among pixels for image features acquired during a single flyover. 2D-CNNs trained on images from a single day were most accurate when images were taken during booting stage or later, with RMSE ranging from 7.4 to 8.2% of the mean yield. A primary benefit of convolutional autoencoder-like models (based on analyses of prediction maps and feature importance) is the spatial denoising effect that corrects yield predictions for individual pixels based on the values of vegetation index and thermal features for nearby pixels. Our results highlight the promise of convolutional autoencoders for UAV-based yield prediction in rice.

A patient tumour-on-a-chip system for personalised investigation of radiotherapy based treatment regimens.

Development of personalised cancer models to predict response to radiation would benefit patient care; particularly in malignancies where treatment resistance is prevalent. Herein, a robust, easy to use, tumour-on-a-chip platform which maintains precision cut head and neck cancer for the purpose of ex vivo irradiation is described. The device utilises sintered discs to separate the biopsy and medium, mimicking in vivo microvascular flow and diffusion, maintaining tissue viability for 68 h. Integrity of tissues is demonstrated by the low levels of lactate dehydrogenase release and retained histology, accompanied by assessment of cell viability by trypan blue exclusion and flow cytometry; fluid dynamic modelling validates culture conditions. An irradiation jig is described for reproducible delivery of clinically-relevant doses (5 × 2 Gy) to newly-presenting primary tumours (n = 12); the addition of concurrent cisplatin is also investigated (n = 8) with response analysed by immunohistochemistry. Fractionated irradiation reduced proliferation (BrdU, p = 0.0064), increased DNA damage (Æ´H2AX, p = 0.0043) and caspase-dependent apoptosis (caspase-cleaved cytokeratin-18) compared to control; caspase-dependent apoptosis was further increased by concurrent cisplatin compared to control (p = 0.0063). This is a proof of principle study showing the response of cancer tissue to irradiation ex vivo in a bespoke system. The novel platform described has the potential to personalise treatment for patients in a cost-effective manner with applicability to any solid tumour.

Chikungunya Virus Infection-associated Arthralgia in Adult Jamaicans Post-outbreak / Artralgia asociada con la infección del virus de Chikunguña en jamaicanos adultos con posterioridad al brote

ABSTRACT Objective: To report demographic and self-reported clinical characteristics associated with persistent and severe arthralgia 8-12 months post-chikungunya virus (CHIKV) infection. Methods: A cross-sectional study of 306 adults who self-reported CHIKV infection was conducted. Subjects were consecutively enrolled at public primary healthcare centres in urban and rural areas in Jamaica. Adults with arthralgic conditions were compared with those who reported no arthralgia. Binary logistic regression models were used to determine demographic and self-reported clinical factors associated with severe arthralgia and persistent arthralgia. Results: Most subjects (70.3%) reported arthralgia after CHIKV outbreak (age: 47.6 ± 18.5 years). Medical consultation (36.2%) and laboratory confirmation (1.4%) were low. The prevalence of persistent and severe arthralgia in the previous month was 30.3% and 27.5%, respectively. Severe arthralgia was associated with the female gender (odds ratio (OR): 2.44; 95% confidence level (CI): 1.08, 5.52) and pre-existing arthritis (OR: 3.78; 95% CI: 1.23, 11.62). Females showed a greater likelihood of persistent arthralgia (OR: 2.18; 95% CI: 1.09, 4.39). Conclusion: Self-perceived arthralgia was an important feature 8-12 months post-CHIKV infection and has implications for the recognition and management of arthritis/rheumatic conditions.

RESUMEN Objetivo: Reportar las características clínicas demográficas y auto-reportadas asociadas con una artralgia persistente y severa de 8-12 meses tras la infección del virus de chikunguña (CHIKV). Métodos: Se llevó a cabo un estudio transversal de 306 adultos que auto-reportaron su infección de CHIKV. Los sujetos fueron alistados consecutivamente en centros públicos de atención primaria en zonas urbanas y rurales de Jamaica. Los adultos con condiciones artrálgicas fueron comparados con adultos que no reportaron artralgia alguna. Los modelos de regresión logística binaria fueron utilizados para determinar los factores clínicos demográficos y auto-reportados que se asocian con artralgia severa y artralgia persistente. Resultados: La mayoría de los sujetos (70.3%) reportaron artralgia después del brote de CHIKV (edad: 47.6 ± 18.5 años). La consulta médica (36.2%) y la confirmación del laboratorio (1.4%) fueron bajas. La prevalencia de la artralgia persistente y la severa en el mes anterior fue de 30.3%y 27.5%, respectivamente. La artralgia severa estuvo asociada al género femenino (odds-ratio (OR): 2.44; intervalo de confianza (IC): 1.08, 5.52), y artritis preexistente (OR: 3.78; 95% (IC: 1.23, 11.62). Las hembras mostraron una mayor probabilidad de artralgia persistente (OR: 2.18; 95% IC: 1.09, 4.39). Conclusión: La artralgia auto-percibida fue una característica importante de la infección post-CHIKV de 8-12 meses, y tiene implicaciones para el reconocimiento y tratamiento de la artritis y las condiciones reumáticas.

Earthworm Preference Bioassays to Evaluate Land Management Practices.

Earthworm preference tests, especially in soil-dosed exposures, can be an informative tool for assessing land management practices. Agricultural management intended to increase crop yield and improve soil sustainability includes physical manipulation of topsoil through conventional tillage, reduced or no-tillage, and/or winter cover crops. Soil amendments include the addition of inorganic nitrogen or organic nitrogen derived from soil amendments including biosolids from sewage treatment plants, poultry litter, or locally available industrial effluent. This study used 48-h Eisenia fetida preference tests to assess impacts of agricultural management practices on soil macrofauna. Although in laboratory-dosed exposures, E. fetida preferred biosolid-dosed soils (80 %-95 % recovery) over control soils, the same results were not found with field soils receiving biosolid amendments (33 % recovery). Poultry litter-amended soils (68 % recovery) were preferred over control soils. No differences were measured between tilled fields and controls, and earthworms preferred control soils over those from fields with no-tillage and cover crops. Soil assessments through laboratory exposures such as these allows science-based agricultural management decisions to maintain or improve soil health.

Ethanol fermentation of energy beets by self-flocculating and non-flocculating yeasts.

Specialized varieties of sugar beets (Energy Beets™) are being developed for producing industrial sugars in Arkansas' Mississippi River Delta. To evaluate their suitability for producing regional fermentation feedstocks, we report initial cultivation trials and ethanol fermentation of raw beet juice and combined juice with pulp mash (JPM) liquefied with enzymes, comparing ethanol yields under different regimes by self-flocculating and non-flocculating yeasts. Nine varieties produced root yields averaging 115Mg/ha and 18.5% sucrose contents. Raw beet juice fermentation yielded ethanol up to 0.48g/g (sugar). JPM was directly fermented through either a sequential (SeqSF) or simultaneous saccharification and fermentation (SSF) process. For both yeast types, SSF was a more efficient process than SeqSF, with ethanol yields up to 0.47g/g (sugar) and volumetric productivity up to 7.81g/L/h. These results indicate the self-flocculating yeast is suitable for developing efficient bioprocesses to ferment industrial sugar from energy beets.

Measuring the accuracy of different ways to identify the 'at-risk' foot in routine clinical practice.

AIMS: We aimed to identify which individual risk factors best predict foot ulceration in routine clinical practice and whether an integrated clinical tool is a better screening tool for future foot ulceration. METHODS: Routinely collected clinical information on foot and general diabetes indicators were recorded on the regional diabetes electronic register. Follow-up data on foot ulceration were collected from the same electronic record, the local multidisciplinary foot clinic and community and hospital podiatry paper records. Data were electronically linked to see which criteria best predicted future foot ulceration. RESULTS: Foot risk scores were recorded on 3719 patients (44% female, mean age 59±15years) across community and hospital clinics. Overall, 851 (22.9%) had insensitivity to monofilaments, in 629 (17.2%) both pulses were absent and 184 (4.9%) had a prior ulcer. In multivariate analysis, the strongest predictors of foot ulceration were prior ulcer, insulin treatment, absent monofilaments, structural abnormality and proteinuria and retinopathy. The sensitivity of predicting foot ulceration was 52% for prior ulcer, 61% for absent monofilaments, 75% for 'high risk' on an integrated risk score and 91% for high and moderate risk combined. The corresponding specificities were 99, 81, 89 and 61%. Positive likelihood ratio was 52 for prior ulcer and 6.8 for foot risk, with negative likelihood ratios of 0.48 and 0.15, respectively. CONCLUSIONS: Integrated foot risk scores are more sensitive than individual clinical criteria in predicting future foot ulceration and are likely to be better screening tools, where excluding false negative results is of paramount importance.

Validation of the pedigree assessment tool (PAT) in families with BRCA1 and BRCA2 mutations.

BACKGROUND: The lifetime risk of breast cancer (BC) in patients with hereditary breast cancer syndromes is as high as 80%. The Pedigree Assessment Tool (PAT) is a scoring system to aid in identifying these patients. This validation study compares the PAT to BRCA gene mutation probability models in predicting suitability for genetic referral. METHODS: Retrospective review identified subjects undergoing genetic counseling and BRCA testing from 2001 to 2008 at two institutions. PAT score and BRCA mutation probabilities were calculated using Myriad II and Penn II models. Comparisons were made between models in ability to discriminate patients appropriate for genetic evaluation based on accuracy in predicting a positive test result. RESULTS: Records evaluated represent 520 families. BRCA testing revealed 146 mutation-positive and 374 mutation-negative families. c-Statistic analysis was used to compare the discriminating ability of the models to correctly assign families as mutation (+) and (-). Both the PAT and Penn II model outperformed the Myriad II model. Using a threshold PAT score >or=8 and mutation probability >or=10% to assign families as mutation (+) versus (-), sensitivity, specificity, and positive and negative predictive values were calculated for each model. The PAT was more sensitive than the Myriad II model and more specific than the Penn II model. CONCLUSIONS: In overall performance, the PAT is at least comparable to the Myriad II and Penn II models in screening women appropriate for genetic referral. Simplicity and identification of families with non-BRCA hereditary BC syndromes suggest that the PAT is better suited for BC risk screening.

Evaluation of a polyacrylamide soil additive to reduce agricultural-associated contamination.

Polyacrylamide is an effective water treatment product used to reduce suspended sediment and associated contaminants. An anionic polyacrylamide-containing product was tested for sediment and associated contaminant reduction and potential toxicity in agricultural irrigation and rainfall runoff. The product effectively reduced turbidity, total suspended solids, and phosphate concentrations in the field when compared to the untreated runoff waters. Acute survival of Ceriodaphnia dubia and Pimephales promelas was not decreased compared to laboratory controls. No significant increases in toxicity were measured in 10-d sediment toxicity tests with Chironomus dilutus. Product applications were effective in controlling sediment and nutrient contamination without increasing measured toxicity.

Behavioural flexibility in individuals with Angelman syndrome, Down syndrome, non-specific intellectual disability and Autism spectrum disorder.

BACKGROUND: Little is known about behavioural flexibility in children and adults with Angelman syndrome and whether people with this syndrome have more or less problems in being behaviourally flexible as compared with other people. METHOD: Behavioural flexibility scores were assessed in 129 individuals with Angelman syndrome using 11 items from the Behavioural Flexibility Rating Scale-Revised (Green et al. 2007). Level of behavioural flexibility scores in individuals with Angelman syndrome (N = 129) was compared with that of people with non-specific intellectual disability (ID) (N = 90), Down syndrome (N = 398) and Autism spectrum disorder (N = 235). RESULTS: Comparative analyses show that individuals with Angelman syndrome were more flexible than those with non-specific ID (P < 0.001) and those with Autism spectrum disorder (P < 0.01). There were no differences in behavioural flexibility scores between individuals with Angelman syndrome and those with Down syndrome (P = 0.94). CONCLUSION: It is concluded that individuals with Angelman syndrome are comparatively flexible in their behaviour.

Stratification of foot ulcer risk in patients with diabetes: a population-based study.

This trial assessed whether a simple clinical tool can be used to stratify patients with diabetes, according to risk of developing foot ulceration. This was a prospective, observational follow-up study of 3526 patients with diabetes (91% type 2 diabetes) attending for routine diabetes care. Mean age was 64.7 (range 15-101) years and duration of diabetes was 8.8 (+/-1.5 SD) years. Patients were categorised into 'low' (64%), 'moderate' (23%) or 'high' (13%) risk of developing foot ulcers by trained staff using five clinical criteria during routine patient care. During follow-up (1.7 years), 166 (4.7%) patients developed an ulcer. Foot ulceration was 83 times more common in high risk and six times more in moderate risk, compared with low-risk patients. The negative predictive value of a 'low-risk score' was 99.6% (99.5-99.7%; 95% confidence interval). This clinical tool accurately predicted foot ulceration in routine practice and could be used direct scarce podiatry resources towards those at greatest need.

Transferring AAC intervention to the home.

PURPOSE: To evaluate the acquisition of AAC skills during an initial clinical trial and assess subsequent transfer of the training to the home setting. METHOD: A 12-year-old male with autism was first seen in a clinical setting to establish the use of a voice-output communication device. After learning to use the device to request access to preferred objects in the clinical trial, the intervention was transferred to the home. Follow-up with the parent was conducted via e-mail and telephone. Videotapes were made of initial home-based sessions to enable evaluation of the participant's progress. RESULTS: The programme was successful in teaching the participant to use a portable AAC device to make requests during the clinical trial and then in two home-based activities. CONCLUSION: An initial clinical trial with follow-up support for parents may be an efficient method for beginning AAC intervention and transferring the training procedures to the home setting.

Nursing the patient with severe communication impairment.

BACKGROUND: Effective communication with patients is critical to effective nursing practice. Surprisingly, there is little information on nurses' experiences in caring for patients who are unable to speak. PURPOSE AND METHOD: This study provides descriptive information from interviews with 20 nurses who cared for patients with severe communication impairment. The interview protocol explored positive and negative experiences of nursing patients with severe communication impairment. Frequency counts and descriptive analyses were conducted to identify the major themes emerging from the interviews. RESULTS: The results suggest that nurse-patient communication is difficult when the patient has severe communication impairment, although some nurses discovered effective strategies to facilitate communication with such patients. Many of the difficulties could be viewed as a breakdown in understanding arising from the lack of a readily interpretable communication system that could be used by nurse and patient. CONCLUSIONS: The results suggest a need for training nurses in the use of alternative modes of communication. Nurses also need access to a variety of simple augmentative communication devices for use with patients who are unable to speak. Finally, nurses should collaborate with speech pathologists on the development of preadmission information and bedside training for people who are admitted to hospital with severe communication impairment.

Combined expectancies: event-related potentials reveal the early benefits of spatial attention that are obscured by reaction time measures.

Visual spatial attention has been likened to a "spotlight" that selectively facilitates the perceptual processing of events at covertly attended locations. However, if participants have advance knowledge of the likely location of an impending target and the likely response it will require, facilitation in response performance does not occur for targets at the expected (or attended) location that require an unexpected response. Event-related potentials (ERPs) were recorded during a discrimination task in which the most likely target location and target response were simultaneously cued prior to target onset. The ERPs showed evidence of enhanced perceptual-level processing for all targets at attended locations. These results suggest that the lack of response facilitation for unexpected targets at attended locations is likely due to postperceptual processes that are activated by the inclusion of nonspatial stimulus expectancies, response expectancies, or both.

Understanding theory of mind in children who are deaf.

Research on theory of mind began in the context of determining whether chimpanzees are aware that individuals experience cognitive and emotional states. More recently, this research has involved various groups of children and various tasks, including the false belief task. Based almost exclusively on that paradigm, investigators have concluded that although "normal" hearing children develop theory of mind by age 5, children who are autistic or deaf do not do so until much later, perhaps not until their teenage years. The present study explored theory of mind by examining stories told by children who are deaf and hearing (age 9-15 years) for statements ascribing behaviour-relevant states of mind to themselves and others. Both groups produced such attributions, although there were reliable differences between them. Results are discussed in terms of the cognitive abilities assumed to underlie false belief and narrative paradigms and the implications of attributing theory of mind solely on the basis of performance on the false belief task.

Response of estrogen receptor containing tumour cells to pure antiestrogens and the calmodulin inhibitor, calmidzolium chloride.

Cell survival is dependent on both external and internally generated signalling processes and current strategies for medical intervention in neoplastic disease are directed towards signal transduction blockade. Redundancy in signalling pathways may mean, however, that a combination of agents is required for the maximal therapeutic benefit. We have explored this idea with regard to the antiestrogen sensitivity of estrogen dependent tumours. Using estrogen receptor (ER) containing tumour cell lines, we have determined whether antiestrogens increase the cytotoxicity of the potent calmodulin inhibitior, calmidzolium chloride (CCl). For the pituitary tumour cell line GH(3), CCl induces a form of apoptotic cell death and co-treatment with the pure antiestrogen, ZM 182780, enhances sensitivity to the calmodulin inhibitor, by at least two fold. In contrast to the pure steroidal antiestrogens, the triphenylethylenes, tamoxifen and 4-hydroxytamoxifen give no enhancing effect on CCl induced cell death. Although CCl induces apoptosis of several ER containing breast cancer cell lines, unlike the pituitary tumour cells, ZM 182780 is unable to increase their sensitivity to calmodulin inhibition. Further studies strongly suggest that cell death in response to calmodulin inhibition is the result of metabolic disruption and that for GH(3) cells, this is enhanced by antiestrogen treatment.

BRCA1 interaction with RNA polymerase II reveals a role for hRPB2 and hRPB10alpha in activated transcription.

The functions of most of the 12 subunits of the RNA polymerase II (Pol II) enzyme are unknown. In this study, we demonstrate that two of the subunits, hRPB2 and hRPB10alpha, mediate the regulated stimulation of transcription. We find that the transcriptional coactivator BRCA1 interacts directly with the core Pol II complex in vitro. We tested whether single subunits from Pol II would compete with the intact Pol II complex to inhibit transcription stimulated by BRCA1. Excess purified Pol II subunits hRPB2 or hRPB10alpha blocked BRCA1- and VP16-dependent transcriptional activation in vitro with minimal effect on basal transcription. No other Pol II subunits tested inhibited activated transcription in these assays. Furthermore, hRPB10alpha, but not hRPB2, blocked Sp1-dependent activation.