Pneumococcal carriage and disease in adults in England 2011-2019: the importance of adults as a reservoir for pneumococcus in communities.

BACKGROUND: Pneumococcal carriage in children has been extensively studied, but carriage in healthy adults and its relationship to invasive pneumococcal disease (IPD) is less understood. METHODS: Nasal wash samples from adults without close contact with young children (Liverpool, UK), 2011-2019, were cultured, and culture-negative samples tested by PCR. Pneumococcal carriage in adults 18-44 years was compared with carriage among PCV-vaccinated children 13-48 months (nasopharyngeal swabs, Thames Valley, UK) and IPD data for England for the same ages for 2014-2019. Age-group specific serotype invasiveness was calculated and used with national IPD data to estimate carriage serotype distributions for adults aged 65+ years. RESULTS: In total 98 isolates (97 carriers) were identified from 1,631 adults aged 18+ years (age and sex standardized carriage prevalence 6.4%), with only three identified solely by PCR. Despite different carriage and IPD serotype distributions between adults and children, serotype invasiveness was highly correlated (R=0.9). Serotypes 3, 37 and 8 represented a higher proportion of adult carriage than expected from direct low-level transmission from children to adults. The predicted carriage serotype distributions for 65+ years aligned more closely with the carriage serotype distribution for young adults than young children. CONCLUSIONS: The nasal wash technique is highly sensitive; additional benefit of PCR is limited. Comparison of carriage serotype distributions suggests some serotypes may be circulating preferentially within these specific young adults. Our data suggest that for some serotypes carried by adults 65+ years, other adults may be an important reservoir for transmission. Age groups such as older children should also be considered.

Exploring the muscle architecture effect on the mechanical behaviour of mouse rotator cuff muscles.

Incorporating detailed muscle architecture aspects into computational models can enable researchers to gain deeper insights into the complexity of muscle function, movement, and performance. In this study, we employed histological, multiphoton image processing, and finite element method techniques to characterise the mechanical dependency on the architectural behaviour of supraspinatus and infraspinatus mouse muscles. While mechanical tests revealed a stiffer passive behaviour in the supraspinatus muscle, the collagen content was found to be two times higher in the infraspinatus. This effect was unveiled by analysing the alignment of fibres during muscle stretch with the 3D models and the parameters obtained in the fitting. Therefore, a strong dependence of muscle behaviour, both active and passive, was found on fibre orientation rather than collagen content.

The utility of parathyroid autofluorescence as an adjunct in thyroid and parathyroid surgery 2023.

Thyroid and parathyroid surgery requires careful dissection around the vascular pedicle of the parathyroid glands to avoid excessive manipulation of the tissues. If the blood supply to the parathyroid glands is disrupted, or the glands are inadvertently removed, temporary and/or permanent hypocalcemia can occur, requiring post-operative exogenous calcium and vitamin D analogues to maintain stable levels. This can have a significant impact on the quality of life of patients, particularly if it results in permanent hypocalcemia. For over a decade, parathyroid tissue has been noted to have unique intrinsic properties known as "fluorophores," which fluoresce when excited by an external light source. As a result, parathyroid autofluorescence has emerged as an intra-operative technique to help with identification of parathyroid glands and to supplement direct visualization during thyroidectomy and parathyroidectomy. Due to the growing body of literature surrounding Near Infrared Autofluorescence (NIRAF), we sought to review the value of using autofluorescence technology for parathyroid detection during thyroid and parathyroid surgery. A literature review of parathyroid autofluorescence was performed using PubMED. Based on the reviewed literature and expert surgeons' opinions who have used this technology, recommendations were made. We discuss the current available technologies (image vs. probe approach) as well as their limitations. We also capture the opinions and recommendations of international high-volume endocrine surgeons and whether this technology is of value as an intraoperative adjunct. The utility and value of this technology seems promising and needs to be further defined in different scenarios involving surgeon experience and different patient populations and conditions.

Clinical Predictors of Pseudohypoxia-Type Pheochromocytomas.

INTRODUCTION: Pheochromocytomas (PCCs) are rare tumors of neural crest origin with divergent transcriptional and metabolic profiles associated with mutational cluster types. Pseudohypoxia-type (PHT) PCCs have a poor prognosis; however diagnostic genetic testing is not always available. We aimed to investigate clinical parameters predictive of PHT PCCs. METHODS: Patients who underwent resection and genetic testing for PCC at two academic centers from 2006-2020 were retrospectively studied. Patients with PHT mutations (SDH-AF2/B/C/D, VHL) were compared to non-pseudohypoxia-type (nonPHT) PCCs to identify widely available clinical parameters predictive of PHT PCCs. Demographic, clinical, and pathologic characteristics were compared using student's T and ANOVA tests. Operative hemodynamic instability was defined as systolic blood pressure (SBP) > 200 mmHg, SBP increase of > 30% relative to baseline, and/or heart rate (HR) > 110 bpm. Mann-Whitney U test was used to assess area under the curve (AUC), sensitivity, and specificity. Recursive partitioning was used to model predictive thresholds for PHT PCC and develop a predictive score. RESULTS: Of the 79 patients included in the cohort, 17 (22%) had PHT and 62 (78%) had nonPHT PCCs. PCC patients with > 2 of the examined predictive clinical parameters (preoperative weight loss [> 10% body weight], elevated preoperative hematocrit [> 50%], normal baseline heart rate [< 100 bpm], and normal plasma metanephrines [< 0.60 nmol/L]) were more likely to have PHT PCCs (AUC = 0.831, sensitivity = 0.882, specificity = 0.694, all p < 0.001). CONCLUSIONS: Widely available preoperative clinical parameters including indicators of erythropoiesis (hemoglobin, hematocrit, and red blood cell count), baseline heart rate, plasma metanephrines, and weight loss may be useful predictors of PHT PCCs and may help guide management of PCCs when genetic testing is unavailable/delayed.

Semi-supervised labelling of the femur in a whole-body post-mortem CT database using deep learning.

A deep learning pipeline was developed and used to localize and classify a variety of implants in the femur contained in whole-body post-mortem computed tomography (PMCT) scans. The results provide a proof-of-principle approach for labelling content not described in medical/autopsy reports. The pipeline, which incorporated residual networks and an autoencoder, was trained and tested using n = 450 full-body PMCT scans. For the localization component, Dice scores of 0.99, 0.96, and 0.98 and mean absolute errors of 3.2, 7.1, and 4.2 mm were obtained in the axial, coronal, and sagittal views, respectively. A regression analysis found the orientation of the implant to the scanner axis and also the relative positioning of extremities to be statistically significant factors. For the classification component, test cases were properly labelled as nail (N+), hip replacement (H+), knee replacement (K+) or without-implant (I-) with an accuracy >97%. The recall for I- and H+ cases was 1.00, but fell to 0.82 and 0.65 for cases with K+ and N+. This semi-automatic approach provides a generalized structure for image-based labelling of features, without requiring time-consuming segmentation.

Spheroscope: A custom-made miniaturized microscope for tracking tumour spheroids in microfluidic devices.

3D cell culture models consisting of self-assembled tumour cells in suspension, commonly known as tumour spheroids, are becoming mainstream for high-throughput anticancer drug screening. A usual measurable outcome of screening studies is the growth rate of the spheroids in response to treatment. This is commonly quantified on images obtained using complex, expensive, optical microscopy systems, equipped with high-quality optics and customized electronics. Here we present a novel, portable, miniaturized microscope made of low-cost, mass-producible parts, which produces both fluorescence and phase-gradient contrast images. Since phase-gradient contrast imaging is based on oblique illumination, epi-illumination is used for both modalities, thus simplifying the design of the system. We describe the system, characterize its performance on synthetic samples and show proof-of-principle applications of the system consisting in imaging and monitoring the formation and growth of lung and pancreas cancer tumour spheroids within custom made microfluidic devices.

International multicentre review of perioperative management and outcome for catecholamine-producing tumours.

BACKGROUND: Surgery for catecholamine-producing tumours can be complicated by intraoperative and postoperative haemodynamic instability. Several perioperative management strategies have emerged but none has been evaluated in randomized trials. To assess this issue, contemporary perioperative management and outcome data from 21 centres were collected. METHODS: Twenty-one centres contributed outcome data from patients who had surgery for phaeochromocytoma and paraganglioma between 2000 and 2017. The data included the number of patients with and without α-receptor blockade, surgical and anaesthetic techniques, complications and perioperative mortality. RESULTS: Across all centres, data were reported on 1860 patients with phaeochromocytoma or paraganglioma, of whom 343 underwent surgery without α-receptor blockade. The majority of operations (78·9 per cent) were performed using minimally invasive techniques, including 16·1 per cent adrenal cortex-sparing procedures. The cardiovascular complication rate was 5·0 per cent overall: 5·9 per cent (90 of 1517) in patients with preoperative α-receptor blockade and 0·9 per cent (3 of 343) among patients without α-receptor blockade. The mortality rate was 0·5 per cent overall (9 of 1860): 0·5 per cent (8 of 517) in pretreated and 0·3 per cent (1 of 343) in non-pretreated patients. CONCLUSION: There is substantial variability in the perioperative management of catecholamine-producing tumours, yet the overall complication rate is low. Further studies are needed to better define the optimal management approach, and reappraisal of international perioperative guidelines appears desirable.

ANTECEDENTES: La cirugía de los tumores productores de catecolaminas puede complicarse por la inestabilidad hemodinámica intraoperatoria y postoperatoria. Se han propuesto distintas estrategias de manejo perioperatorio, pero ninguna ha sido evaluada en ensayos aleatorizados. Para evaluar este tema, se han recogido los datos de los resultados y del manejo perioperatorio contemporáneo de 21 centros. MÉTODOS: Veintiún centros aportaron datos de los resultados de los pacientes operados por feocromocitoma y paraganglioma entre 2000-2017. Los datos incluyeron el número de pacientes con y sin bloqueo del receptor α, las técnicas quirúrgicas y anestésicas, las complicaciones y la mortalidad perioperatoria. RESULTADOS: Los centros en su conjunto aportaron datos de 1.860 pacientes con feocromocitoma y paraganglioma, de los cuales 343 pacientes fueron intervenidos sin bloqueo del receptor α. La gran mayoría (79%) de las cirugías se realizaron utilizando técnicas mínimamente invasivas, incluido un 17% de procedimientos con preservación de la corteza suprarrenal. La tasa de complicaciones cardiovasculares fue de 5,0% en total; 5,9% (90/1517) en pacientes con bloqueo preoperatorio de los receptores α y 0,9% (3/343) en pacientes no pretratados. La mortalidad global fue del 0,5% (9/1860); 0,5% (8/1517) en pacientes pretratados y 0,3% (1/343) en pacientes no tratados previamente. CONCLUSIÓN: Existe una variabilidad sustancial en el manejo perioperatorio de los tumores productores de catecolaminas, aunque la tasa global de complicaciones es baja. Este estudio brinda la oportunidad para efectuar comparaciones sistemáticas entre estrategias de prácticas terapéuticas variables. Se necesitan más estudios para definir mejor el enfoque de manejo óptimo y parece conveniente volver a evaluar las guías internacionales perioperatorias.

Retiro de medicamentos antineoplásicos en un hospital nacional en Costa Rica / Antineoplastic medication pick-up rates in a Costa Rican national hospital

OBJETIVO: Analizar los porcentajes de dosis retiradas de medicamentos oncológicos no incluidos en la Lista Oficial de Medicamentos según el servicio médico prescriptor y la vía de administración del fármaco, en un hospital de tercer nivel de atención en Costa Rica. Métodología: Los datos fueron obtenidos de manera retrospectiva a partir de bases de datos desarrolladas a nivel hospitalario para el control de los medicamentos adquiridos y a partir de los registros de medicamentos despachados. RESULTADOS: Las unidades aprobadas para compra en los Servicios de Oncología y Hematología no son retiradas en su totalidad por los pacientes en tratamiento oncológico. En general, el porcentaje de retiro fue de 90,3% para 98 solicitudes de compra. Existen diferencias estadísticamente significativas en los porcentajes de retiro según el servicio médico prescriptor ( t= -2,68; p = 0,01) y la vía de administración de los medicamentos (t = -2,61; p = 0,01). Del análisis multivariado se desprende que en el Servicio de Oncología Médica el porcentaje de retiro de medicamentos es significativamente menor entre las personas divorciadas (beta = -4,7; p < 0,01) y viudas (beta = -20,5; p = 0,01) en comparación con las personas casadas. CONCLUSIONES: El retiro de medicamentos, si bien no es una forma de medir la adherencia terapéutica, permite establecer una relación primaria entre el paciente y el tratamiento a administrar. El subretiro de medicamentos encontrado mediante este estudio evidencia la necesidad de ampliar la investigación con el fin de conocer los motivos por los que los pacientes no retiran sus tratamientos oncológicos de compra

OBJECTIVE: To analyze the percentage of picked-up doses of oncologic drugs not included in the Essential Medicine List according to the medical prescribing service and the administration route of the drug in a third level hospital in Costa Rica. METHOD: Data was obtained by retrospective analysis from databases developed for the hospital's control of acquired drugs and from the dispatched drug registry. RESULTS: Not all medications acquired through the special drug buying mechanism are picked-up by patients from the Oncology and Hematology Services. Overall, the pick-up rate was 90.3% for the 98 processes analyzed. Significant differences for the picking-up percentages were found for the medical prescribing service (t = -2.68; p = 0.01) and the drug's administration route (t = -2.61; p = 0.01). Multivariate analysis shows that for the Medical Oncology Service, pick-up rate is significantly lower among divorced (Beta = -4.7; p < 0.01) and widowed (Beta = -20.5; p = 0.01) patients compared to married ones. CONCLUSIONS: Even when pick-up rates are not a way to measure therapeutic adherence, they allow to establish a primary relationship between the patient and its treatment. The underpicking of treatments found by this study shows the need to increase the research in order to understand patient's reasons to abandon oncologic treatments that are not included in the Essential Medicine List

Protective effect of PCV vaccine against experimental pneumococcal challenge in adults is primarily mediated by controlling colonisation density.

Widespread use of Pneumococcal Conjugate Vaccines (PCV) has reduced vaccine-type nasopharyngeal colonisation and invasive pneumococcal disease. In a double-blind, randomised controlled trial using the Experimental Human Pneumococcal Challenge (EHPC) model, PCV-13 (Prevenar-13) conferred 78% protection against colonisation acquisition and reduced bacterial intensity (AUC) as measured by classical culture. We used a multiplex qPCR assay targeting lytA and pneumococcal serotype 6A/B cpsA genes to re-assess the colonisation status of the same volunteers. Increase in detection of low-density colonisation resulted in reduced PCV efficacy against colonisation acquisition (29%), compared to classical culture (83%). For experimentally colonised volunteers, PCV had a pronounced effect on decreasing colonisation density. These results obtained in adults suggest that the success of PCV vaccination could primarily be mediated by the control of colonisation density. Studies assessing the impact of pneumococcal vaccines should allow for density measurements in their design.

Cassava flour slurry as a low-cost alternative to commercially available gel for obstetrical ultrasound: a blinded non-inferiority trial comparison of image quality.

OBJECTIVE: To evaluate the quality of ultrasound images obtained with cassava flour slurry (CFS) compared with conventional gel in order to determine objectively whether CFS could be a true low-cost alternative. DESIGN: Blinded non-inferiority trial. SETTING: Obstetrical ultrasound unit in an academic medical centre. POPULATION OR SAMPLE: Women with a singleton pregnancy, undergoing anatomy ultrasounds. METHODS: Thirty pregnant women had standard biometry measures obtained with CFS and conventional gel. Images were compared side-by-side in random order by two blinded sonologists and rated for image resolution, detail and total image quality using a 10-cm visual analogue scale. Ratings were compared using paired t-tests. Participant and sonographer experience was measured using five-point Likert scales. MAIN OUTCOME MEASURES: Image resolution, detail, and total image quality. Participant experience of gel regarding irritation, messiness, and ease of removal. RESULTS: We found no significant difference between perceived image quality obtained with CFS (mean = 6.2, SD = 1.2) and commercial gel (mean = 6.4, SD = 1.2) [t (28) = -1.1; P = 0.3]. Images were not rated significantly differently for either reviewer in any measure, any standardized image or any view of a specific anatomic structure. All five sonographers rated CFS as easy to obtain clear images and easy for patient and machine cleanup. Only one participant reported itching with CFS. CONCLUSIONS: CFS produces comparable image quality to commercial ultrasound gel. The dissemination of these results and the simple CFS recipe could significantly increase access to ultrasound for screening, monitoring and diagnostic purposes in resource-limited settings. FUNDING: This study was internally funded by our department. TWEETABLE ABSTRACT: Low-cost homemade cassava flour slurry creates images equal to commercial ultrasound gel, improving access.

Intraoperative Assessment of Parathyroid Viability using Laser Speckle Contrast Imaging.

Post-surgical hypoparathyroidism and hypocalcemia are known to occur after nearly 50% of all thyroid surgeries as a result of accidental disruption of blood supply to healthy parathyroid glands, which are responsible for regulating calcium. However, there are currently no clinical methods for accurately identifying compromised glands and the surgeon relies on visual assessment alone to determine if any gland(s) should be excised and auto-transplanted. Here, we present Laser Speckle Contrast Imaging (LSCI) for real-time assessment of parathyroid viability. Taking an experienced surgeon's visual assessment as the gold standard, LSCI can be used to distinguish between well vascularized (n = 32) and compromised (n = 27) parathyroid glands during thyroid surgery with an accuracy of 91.5%. Ability to detect vascular compromise with LSCI was validated in parathyroidectomies. Results showed that this technique is able to detect parathyroid gland devascularization before it is visually apparent to the surgeon. Measurements can be performed in real-time and without the need to turn off operating room lights. LSCI shows promise as a real-time, contrast-free, objective method for helping reduce hypoparathyroidism after thyroid surgery.

Polysaccharide-Specific Memory B Cells Predict Protection against Experimental Human Pneumococcal Carriage

Rationale: We have previously demonstrated that experimental pneumococcal carriage enhances immunity and protects healthy adults against carriage reacquisition after rechallenge with a homologous strain. Objectives: To investigate the role of naturally acquired pneumococcal protein and polysaccharide (PS)-specific immunity in protection against carriage acquisition using a heterologous challenge model. Methods: We identified healthy volunteers that were naturally colonized with pneumococcus and, after clearance of their natural carriage episode, challenged them with a heterologous 6B strain. In another cohort of volunteers we assessed 6BPS-specific, PspA-specific, and PspC-specific IgG and IgA plasma and memory B-cell populations before and 7, 14, and 35 days after experimental pneumococcal inoculation. Measurements and Main Results: Heterologous challenge with 6B resulted in 50% carriage among volunteers with previous natural pneumococcal carriage. Protection from carriage was associated with a high number of circulating 6BPS IgG-secreting memory B cells at baseline. There were no associations between protection from carriage and baseline levels of 6BPS IgG in serum or nasal wash, PspA-specific, or PspC-specific memory B cells or plasma cells. In volunteers who did not develop carriage, the number of circulating 6BPS memory B cells decreased and the number of 6BPS plasma cells increased postinoculation. Conclusions: Our data indicate that naturally acquired PS-specific memory B cells, but not levels of circulating IgG at time of pneumococcal exposure, are associated with protection against carriage acquisition

Validation tool for traction force microscopy.

Traction force microscopy (TFM) is commonly used to estimate cells' traction forces from the deformation that they cause on their substrate. The accuracy of TFM highly depends on the computational methods used to measure the deformation of the substrate and estimate the forces, and also on the specifics of the experimental set-up. Computer simulations can be used to evaluate the effect of both the computational methods and the experimental set-up without the need to perform numerous experiments. Here, we present one such TFM simulator that addresses several limitations of the existing ones. As a proof of principle, we recreate a TFM experimental set-up, and apply a classic 2D TFM algorithm to recover the forces. In summary, our simulator provides a valuable tool to study the performance, refine experimentally, and guide the extraction of biological conclusions from TFM experiments.

The Bethesda system for reporting thyroid cytopathology: a single-center experience over 5 years.

BACKGROUND: The Bethesda System for Reporting Thyroid Cytopathology (BSRTC) was developed to refine fine-needle aspiration (FNA) cytology definitions and improve clinical management. This study evaluates the impact of the BSRTC 5 years after its adoption at a single institution. METHODS: A total of 1,625 patients undergoing thyroidectomy in the pre-BSRTC (Group 1: July 2007-January 2009) and post-BSRTC (Group 2: February 2009-September 2013) periods were reviewed. Cytologic diagnoses in Group 1 included non-diagnostic, benign, follicular neoplasm, suspicious for malignancy and malignant. Atypia/follicular lesion of undetermined significance (AUS/FLUS) was included in Group 2. The proportions of each FNA category and malignancy rate per cytologic diagnosis were compared. RESULTS: Fifty-four percent (187/347) of Group 1 patients had a preoperative FNA versus 61 % (777/1278) in Group 2 (p = 0.02). Group 1 FNA results included 3 % non-diagnostic, 48 % benign, 17 % follicular, 13 % suspicious for cancer, and 19 % cancer. Group 2 results included 3 % non-diagnostic, 36 % benign, 9 % follicular, 8 % suspicious for malignancy, 18 % malignant and 26 % AUS/FLUS. In Group 2, the proportions of benign, follicular and suspicious for malignancy FNAs decreased significantly (p < 0.05). In Group 2, there were more indeterminate FNA diagnoses overall (30 vs. 43 %; p < 0.001). The rate of cancer in suspicious for cancer FNA lesions increased from 44 to 65 % (p = 0.07). The AUS/FLUS malignancy rate was 15 %. CONCLUSIONS: Since the adoption of the BSRTC at our institution, the proportion of indeterminate FNAs has increased; however, the diagnostic accuracy of the suspicious for cancer category improved. We recommend periodic review of the utilization and malignancy rates per cytologic category at each institution to help tailor clinical management.

Utilization and impact of repeat biopsy for follicular lesion/atypia of undetermined significance.

BACKGROUND: The Bethesda System for Reporting Thyroid Cytopathology (BSRTC) created a new diagnostic category,follicular lesion/atypia of undetermined significance(FLUS/AUS). The recommended management of FLUS/AUS lesions is repeat biopsy to re-classify the lesion and guide therapy. Prior surgical studies suggest a higher than expected malignancy rate for FLUS/AUS. The present study evaluates a large institutional experience with all FLUS/AUS lesions analyzing use and impact of repeat biopsy. METHODS: A total of 322 patients with FLUS/AUS cytology have been retrospectively identified since adoption of the BSRTC (2/2009­6/2012). Patient demographics, the results of clinical follow-up, repeat biopsy, or surgical pathology results were evaluated. RESULTS: Among the 322 patients, 16 had concurrent cytology of higher acuity and were excluded. For the remaining 306 patients, 101 (33 %) underwent repeat biopsy, yielding 49 (48.5 %) with FLUS/AUS, 43 (42.5 %)with benign cytology, and 9 (9 %) with higher acuity cytology. Among the 205 patients without repeat biopsy,117 (57 %) chose thyroidectomy, and 88 (43 %) are being observed. Overall, 170/306 (55.6 %) patients underwent surgery to remove the index lesion, yielding a malignancy rate of 16.5 %. In contrast, the malignancy rate for the entire cohort was 28/306 (9 %). CONCLUSIONS: Repeat biopsy was underutilized in FLUS/AUS cases. Repeat biopsy allows a significant proportion of FLUS/AUS patients without other indications for surgery to move to surveillance. In patients who have indications for thyroidectomy regardless of FLUS/AUS results,repeat biopsy does not appear necessary. Malignancy and thyroidectomy rates were similar among patients who did or did not have a repeat biopsy. Further data must be obtained to determine the long-term outcomes for surveillance of FLUS/AUS lesions in patients who do not undergo surgical removal.

Identification of serologic markers for school-aged children with congenital rubella syndrone

BACKGROUND: Congenital rubella syndrome (CRS) case identification is challenging in older children since laboratory markers of congenital rubella virus (RUBV) infection do not persist beyond age 12 months. METHODS: We enrolled children with CRS born between 1998 and 2003 and compared their immune responses to RUBV with those of their mothers and a group of similarly aged children without CRS. Demographic data and sera were collected. Sera were tested for anti-RUBV immunoglobulin G (IgG), IgG avidity, and IgG response to the 3 viral structural proteins (E1, E2, and C), reflected by immunoblot fluorescent signals. RESULTS: We enrolled 32 children with CRS, 31 mothers, and 62 children without CRS. The immunoblot signal strength to C and the ratio of the C signal to the RUBV-specific IgG concentration were higher (P < .029 for both) and the ratio of the E1 signal to the RUBV-specific IgG concentration lower (P = .001) in children with CRS, compared with their mothers. Compared with children without CRS, children with CRS had more RUBV-specific IgG (P < .001), a stronger C signal (P < .001), and a stronger E2 signal (P ≤ .001). Two classification rules for children with versus children without CRS gave 100% specificity with >65% sensitivity. CONCLUSIONS: This study was the first to establish classification rules for identifying CRS in school-aged children, using laboratory biomarkers. These biomarkers should allow improved burden of disease estimates and monitoring of CRS control programs. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Numerical estimation of 3D mechanical forces exerted by cells on non-linear materials.

The exchange of physical forces in both cell-cell and cell-matrix interactions play a significant role in a variety of physiological and pathological processes, such as cell migration, cancer metastasis, inflammation and wound healing. Therefore, great interest exists in accurately quantifying the forces that cells exert on their substrate during migration. Traction Force Microscopy (TFM) is the most widely used method for measuring cell traction forces. Several mathematical techniques have been developed to estimate forces from TFM experiments. However, certain simplifications are commonly assumed, such as linear elasticity of the materials and/or free geometries, which in some cases may lead to inaccurate results. Here, cellular forces are numerically estimated by solving a minimization problem that combines multiple non-linear FEM solutions. Our simulations, free from constraints on the geometrical and the mechanical conditions, show that forces are predicted with higher accuracy than when using the standard approaches.

The Americas: paving the road toward global measles eradication.

BACKGROUND: The Region of the Americas set a goal of interrupting endemic measles virus transmission by the end of 2000. This decision was primarily based on rapid decreases in measles disease burden in pioneering countries that implemented Pan American Health Organization-recommended vaccination and surveillance strategies. Review of these strategies may inform measles elimination efforts in other regions. METHODS: Results from the implementation of the measles elimination strategy in the Americas were compiled and analyzed over a 30-year period, which was divided into 4 phases: the early years of the Expanded Program on Immunization (1980-1986); the start-up phase for elimination (1987-1994); the elimination phase (1995-2002); and the postelimination phase (2003-2010). Factors that contributed to elimination and the challenges confronted during the postelimination phase are discussed. RESULTS: An analysis of vaccination strategies over time highlights the transition from monovalent measles vaccine to the incorporation of measles-mumps-rubella vaccine administered in the routine program. Regional vaccination coverage increased during the period 1987-2010, sustained at ≥90% since 1998. Measles elimination efforts led to the implementation of 157 national vaccination campaigns, vaccinating a total of 440 million persons. Endemic measles virus transmission was interrupted in 2002. After elimination, measles importations and associated outbreaks occurred. Measles incidence has remained at <1 case per 1 million population since 2002. CONCLUSIONS: The success of measles elimination strategies in the Americas suggests that global measles eradication is attainable.

Non-rigid consistent registration of 2D image sequences.

We present a novel algorithm for the registration of 2D image sequences that combines the principles of multiresolution B-spline-based elastic registration and those of bidirectional consistent registration. In our method, consecutive triples of images are iteratively registered to gradually extend the information through the set of images of the entire sequence. The intermediate results are reused for the registration of the following triple. We choose to interpolate the images and model the deformation fields using B-spline multiresolution pyramids. Novel boundary conditions are introduced to better characterize the deformations at the boundaries. In the experimental section, we quantitatively show that our method recovers from barrel/pincushion and fish-eye deformations with subpixel error. Moreover, it is more robust against outliers--occasional strong noise and large rotations--than the state-of-the-art methods. Finally, we show that our method can be used to realign series of histological serial sections, which are often heavily distorted due to folding and tearing of the tissues.