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During recent years, many research group interested in the study of organizational networks from different fields, e.g. studies of behavior of cities growth following the fractal theory. Considering the fractal analysis as a strong tools to analyse the relation between grow of cities and its relation with health center distribution. The propose of this paper is to develop a methodology based on a fractal analysis framework of Chilean public health networks, the population growth of cities and the location of health centers. To produce empirical approach for the analysis of the locations of health centers and its effects. On the other hand the health has been related to other sciences, a clear example is the physics and the mathematics, where we found many studies related with the geometry to understood the nature of the multiple natural shapes, its developed was called fractal nature or mathematic fractal model, this approach consider the different scales. For this reason, we present in this paper some preliminary ideas and some initial results of the analysis of the complex and fractal behavior of urban expansion, and its relation to the location of public health centers through simple counters algorithms and spectral methods using ImaCal software. The study health patterns will become a useful tool for understanding human flow and behavior of health center, where using a traditional measurement as equipment has serious problems and limitations.

Introducción: En pacientes mayores de 65 años existe una reserva fisiológica deteriorada, lo que conlleva a que las complicaciones posquirúrgicas sean más frecuentes. La extensión de la enfermedad al momento del diagnóstico (etapa clínica) y la resección completa de la tumoración son dos factores de riesgo independientes, que influyen directamente en la supervivencia. Objetivo: Describir los factores que influyen en la morbilidad y mortalidad, en pacientes mayores de 65 años postoperados de cirugía colorrectal. Material y métodos: Estudio retrospectivo, observacional y descriptivo. Se incluyeron 105 pacientes con cáncer de colon postoperados de cirugía colorrectal, en el periodo comprendido entre enero 2004 y diciembre 2009. Se estratificaron en menores y mayores de 65 años para comparar la comorbilidad prequirúrgica, así como la morbilidad y mortalidad a 30 días postoperatoria. Resultados: Cincuenta y seis de los 105 (53,3%) pacientes eran ≤ 65 años. El 42,8% presentó complicaciones, siendo las más frecuentes aquellas que se presentaron tempranamente y de menor severidad; las tardías ocurrieron con mayor frecuencia en pacientes ≤ 65 vs mayores de 65 años (16,0% vs 10,2%). Se observó sobrepeso (IMC > 25 kg/m2) en el 35,0% de nuestra población. Los pacientes mayores de 65 años tuvieron menos comorbilidades. Las causas más comunes de reintervención fueron dehiscencia de anastomosis y hemorragia postoperatoria. La mortalidad del grupo fue 6,6%, siendo la sepsis la causa más frecuente de muerte. Conclusión: La cirugía colorrectal en mayores de 65 años tiene una frecuencia aceptable de complicaciones y una baja tasa de mortalidad. Nuestros resultados sugieren que los pacientes mayores de 65 años, deben tratarse con la misma expectativa de curación que los pacientes más jóvenes.

Local Diffusion and the topological structure of vorticity and velocity fields is measured in the transition from a homogeneous linearly stratified fluid to a cellular or layered structure by means of convective cooling and/or heating. Patterns arise by setting up a convective flow generated by an array of Thermoelectric devices (Peltier/Seebeck cells) these are controlled generating a buoyant heat flux. The experiments described here investigate high Prandtl number mixing using brine and fresh water in order to form density interfaces and low Prandtl number mixing with temperature gradients. The set of dimensionless parameters define conditions of numeric and small scale laboratory modeling of environmental flows. Fields of velocity, density and their gradients were computed and visualized using the open software tools of DigiFlow. When convective heating and cooling takes place in the side wall of a stratified enclosed cell, the combination of internal waves and buoyancy driven turbulence is much more complicated if the Rayleigh and Reynolds numbers are high. Higher order moments calculations and intermittency are important in order to study mixing in complex flows Here some examples are shown using the Thermoelectric Convection Didactive Device (TCDD) built by BEROTZA, mainly in a symmetric two dimensional pattern, but many other combinations, using heating-cooling and angles with the vertical are possible in order to validate more complex numerical experiments.

Background: Histopathological growth patterns are one of the strongest prognostic factors in patients with resected colorectal liver metastases. Development of an efficient, objective and ideally automated histopathological growth pattern scoring method can substantially help the implementation of histopathological growth pattern assessment in daily practice and research. This study aimed to develop and validate a deep-learning algorithm, namely neural image compression, to distinguish desmoplastic from non-desmoplastic histopathological growth patterns of colorectal liver metastases based on digital haematoxylin and eosin-stained slides., Methods: The algorithm was developed using digitalized whole-slide images obtained in a single-centre (Erasmus MC Cancer Institute, the Netherlands) cohort of patients who underwent first curative intent resection for colorectal liver metastases between January 2000 and February 2019. External validation was performed on whole-slide images of patients resected between October 2004 and December 2017 in another institution (Radboud University Medical Center, the Netherlands). The outcomes of interest were the automated classification of dichotomous hepatic growth patterns, distinguishing between desmoplastic hepatic growth pattern and non-desmoplatic growth pattern by a deep-learning model; secondary outcome was the correlation of these classifications with overall survival in the histopathology manual-assessed histopathological growth pattern and those assessed using neural image compression., Results: Nine hundred and thirty-two patients, corresponding to 3.641 whole-slide images, were reviewed to develop the algorithm and 870 whole-slide images were used for external validation. Median follow-up for the development and the validation cohorts was 43 and 29 months respectively. The neural image compression approach achieved significant discriminatory power to classify 100% desmoplastic histopathological growth pattern with an area under the curve of 0.93 in the development cohort and 0.95 upon external validation. Both the histopathology manual-scored histopathological growth pattern and neural image compression-classified histopathological growth pattern achieved a similar multivariable hazard ratio for desmoplastic versus non-desmoplastic growth pattern in the development cohort (histopathology manual score: 0.63 versus neural image compression: 0.64) and in the validation cohort (histopathology manual score: 0.40 versus neural image compression: 0.48)., Conclusions: The neural image compression approach is suitable for pathology-based classification tasks of colorectal liver metastases., (© The Author(s) 2024. Published by Oxford University Press on behalf of BJS Foundation Ltd.)

The tumor microenvironment (TME), composed of and influenced by a heterogeneous set of cancer cells and an extracellular matrix, plays a crucial role in cancer progression. The biophysical aspects of the TME (namely, its architecture and mechanics) regulate interactions and spatial distributions of cancer cells and immune cells. In this review, we discuss the factors of the TME-notably, the extracellular matrix, as well as tumor and stromal cells-that contribute to a pro-tumor, immunosuppressive response. We then discuss the ways in which cells of the innate and adaptive immune systems respond to tumors from both biochemical and biophysical perspectives, with increased focus on CD8+ and CD4+ T cells. Building upon this information, we turn to immune-based antitumor interventions-specifically, recent biophysical breakthroughs aimed at improving CAR-T cell therapy., Competing Interests: The authors have no conflicts to disclose., (© 2024 Author(s).)

Objectives: Extremes of patient body mass index are associated with difficult intubation and increased morbidity in adults. We aimed to determine the association between being underweight or obese with adverse airway outcomes, including adverse tracheal intubation (TI)-associated events (TIAEs) and/or severe peri-intubation hypoxemia (pulse oximetry oxygen saturation < 80%) in critically ill children., Design/setting: Retrospective cohort using the National Emergency Airway for Children registry dataset of 2013-2020., Patients: Critically ill children, 0 to 17 years old, undergoing TI in PICUs., Interventions: None., Measurements and Main Results: Registry data from 24,342 patients who underwent TI between 2013 and 2020 were analyzed. Patients were categorized using the Centers for Disease Control and Prevention weight-for-age chart: normal weight (5th-84th percentile) 57.1%, underweight (< 5th percentile) 27.5%, overweight (85th to < 95th percentile) 7.2%, and obese (≥ 95th percentile) 8.2%. Underweight was most common in infants (34%); obesity was most common in children older than 8 years old (15.1%). Underweight patients more often had oxygenation and ventilation failure (34.0%, 36.2%, respectively) as the indication for TI and a history of difficult airway (16.7%). Apneic oxygenation was used more often in overweight and obese patients (19.1%, 19.6%) than in underweight or normal weight patients (14.1%, 17.1%; p < 0.001). TIAEs and/or hypoxemia occurred more often in underweight (27.1%) and obese (24.3%) patients ( p < 0.001). TI in underweight children was associated with greater odds of adverse airway outcome compared with normal weight children after adjusting for potential confounders (underweight: adjusted odds ratio [aOR], 1.09; 95% CI, 1.01-1.18; p = 0.016). Both underweight and obesity were associated with hypoxemia after adjusting for covariates and site clustering (underweight: aOR, 1.11; 95% CI, 1.02-1.21; p = 0.01 and obesity: aOR, 1.22; 95% CI, 1.07-1.39; p = 0.002)., Conclusions: In underweight and obese children compared with normal weight children, procedures around the timing of TI are associated with greater odds of adverse airway events., Competing Interests: Ms. Napolitano’s, Dr. Shults’s, Dr. Nadkarni’s, and Dr. Nishisaki’s institution received funding from the Agency for Healthcare Research and Quality (R18HS024511). Ms. Napolitano’s institution received funding from Dräger, Actuated Medical, and Philips Respironics; they received support for article research from Timpel and VERO-Biotech. Dr. Krawiec received funding from New England Journal of Medicine Healer Cases and Carle Illinois School of Medicine Admissions Committee. Dr. Polikoff received funding from Novavax. Dr. Lee’s institution received funding from National Research Medical Council, Singapore. Dr. Shenoi is an elected member of the Society of Critical Care Medicine (SCCM) Council of the SCCM. Dr. Peihl disclosed that he is founder and Chief Medical Officer of 410 Medical; his institution received funding the Department of Defense (grants: USSOCOM W81XWH-22-C-0002, USAF SBIR AF212-CSO1 Phase II, F2-15653 USAF, SBIR AF211-CSO1 Phase II, F2-15254). Dr. Hasegawa disclosed work for hire. Dr. Nishisaki’s institution received funding from Chiesi USA, AHRA, and the National Institute of Child Health and Human Development. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Importance: Chronic obstructive pulmonary disease (COPD) is a respiratory condition that is associated with significant health and economic burden worldwide. Previous studies assessed the global current-day prevalence of COPD, but to better facilitate resource planning and intervention development, long-term projections are needed., Objective: To assess the global burden of COPD through 2050, considering COPD risk factors., Design, Setting, and Participants: In this modeling study, historical data on COPD prevalence was extracted from a recent meta-analysis on 2019 global COPD prevalence, and 2010 to 2018 historical prevalence was estimated using random-effects meta-analytical models. COPD risk factor data were obtained from the Global Burden of Disease database., Main Outcomes and Measures: To project global COPD prevalence to 2050, generalized additive models were developed, including smoking prevalence, indoor and outdoor air pollution, and development indices as predictors, and stratified by age, sex, and World Bank region., Results: The models estimated that the number of COPD cases globally among those aged 25 years and older will increase by 23% from 2020 to 2050, approaching 600 million patients with COPD globally by 2050. Growth in the burden of COPD was projected to be the largest among women and in low- and middle-income regions. The number of female cases was projected to increase by 47.1% (vs a 9.4% increase for males), and the number of cases in low- and middle-income regions was expected to be more than double that of high-income regions by 2050., Conclusions and Relevance: In this modeling study of future COPD burden, projections indicated that COPD would continue to affect hundreds of millions of people globally, with disproportionate growth among females and in low-middle income regions through 2050. Further research, prevention, and advocacy are needed to address these issues so that adequate preparation and resource allocation can take place.

Objective: The US government detains hundreds of thousands of migrants across a network of facilities each year. This research aims to evaluate the completeness of standards across US detention agencies to protect the health and dignity of migrants., Design: Five documents from three US agencies were examined in a systematic review: Immigration and Customs Enforcement (ICE; 3), Customs and Border Protection (CBP; 1) and Office of Refugee Resettlement (ORR; 1). Standards within five public health categories (health, hygiene, shelter, food and nutrition, protection) were extracted from each document and coded by subcategory and area. Areas were classified as critical, essential or supportive. Standards were measured for specificity, measurability, attainability, relevancy and timeliness (SMART), resulting in a sufficiency score (0%-100%). Average sufficiency scores were calculated for areas and agencies., Results: 711 standards were extracted within 5 categories, 12 subcategories and 56 areas. 284 standards of the 711 standards were included in multiple (2-7) areas, resulting in 1173 standards counted as many times as each was included. On average, 85.4% of standards were specific, 87.1% measurable, 96.6% attainable and 74.9% time-bound. All standards were considered relevant. CBP standards were the least sufficient across all other SMART components, when compared with ICE and ORR., Conclusions: There are disparate detention standards based on agencies' mandates and type of facility contracts. Migrants should be ensured of their public health rights and services in all spaces they occupy, and for any length of time regardless of who manages the facility. As long as detention remains a policy, the US should develop comprehensive, consistent and complementary standards for all detention facilities or pursue alternatives to detention., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Determine if apneic oxygenation (AO) delivered via nasal cannula during the apneic phase of tracheal intubation (TI), reduces adverse TI-associated events (TIAEs) in children., Methods: AO was implemented across 14 pediatric intensive care units as a quality improvement intervention during 2016-2020. Implementation consisted of an intubation safety checklist, leadership endorsement, local champion, and data feedback to frontline clinicians. Standardized oxygen flow via nasal cannula for AO was as follows: 5 L/min for infants (< 1 year), 10 L/min for young children (1-7 years), and 15 L/min for older children (≥ 8 years). Outcomes were the occurrence of adverse TIAEs (primary) and hypoxemia (SpO 2  < 80%, secondary)., Results: Of 6549 TIs during the study period, 2554 (39.0%) occurred during the pre-implementation phase and 3995 (61.0%) during post-implementation phase. AO utilization increased from 23 to 68%, p < 0.001. AO was utilized less often when intubating infants, those with a primary cardiac diagnosis or difficult airway features, and patient intubated due to respiratory or neurological failure or shock. Conversely, AO was used more often in TIs done for procedures and those assisted by video laryngoscopy. AO utilization was associated with a lower incidence of adverse TIAEs (AO 10.5% vs. without AO 13.5%, p < 0.001), aOR 0.75 (95% CI 0.58-0.98, p = 0.03) after adjusting for site clustering (primary analysis). However, after further adjusting for patient and provider characteristics (secondary analysis), AO utilization was not independently associated with the occurrence of adverse TIAEs: aOR 0.90, 95% CI 0.72-1.12, p = 0.33 and the occurrence of hypoxemia was not different: AO 14.2% versus without AO 15.2%, p = 0.43., Conclusion: While AO use was associated with a lower occurrence of adverse TIAEs in children who required TI in the pediatric ICU after accounting for site-level clustering, this result may be explained by differences in patient, provider, and practice factors. Trial Registration Trial not registered., (© 2023. The Author(s).)

The United States of America (US) detains more migrants than any other nation. Customs and Border Patrol (CBP) and Immigration and Customs Enforcement (ICE) detain adults and families under the Department of Homeland Security, while unaccompanied minors are housed under the Office of Refugee Resettlement (ORR) within the Department of Health and Human Services. Migrants are subject to the standards and oversight of each individual agency and facility where they are detained. This paper presents an analysis of whether the current US migrant detention system upholds the standards of each agency to maintain the health of migrants. A review of peer and grey literature, along with interviews with key informants (KI) who had worked in or visited ICE, CBP, or ORR facilities since January 2018 were undertaken. Analysis of the literature review and KI interviews covered five thematic areas: health, protection of vulnerable populations, shelter, food and nutrition, and hygiene. Thirty-nine peer-reviewed publications and 28 US Office of Inspector General reports from 2010 to 2020 were reviewed. Seventeen KI interviews were conducted. Though all three detention agencies had significant areas of concern, CBP's inability to abide by its health standards was particularly alarming. The persistence of low compliance with standards stemmed from weak accountability mechanisms, minimal transparency, and inadequate capacity to provide essential services. We have five recommendations: (1) expand independent monitoring and evaluation mechanisms; (2) standardize health standards across the three agencies; (3) develop a systematic evaluation tool to help external visitors, including members of Congress, assess the degree of implementation of standards; (4) enforce consequences for private contractors who violate standards; and (5) restrict the use of waivers that allow detention facilities to circumvent compliance with standards. Ultimately, the US federal government should explore and implement alternatives to detention to maintain the health and dignity of the individuals under its care., Competing Interests: The authors declare no conflict of interest, including financial issues wrt this paper entitled: The United States Detention System for Migrants: Patterns of Negligence and Inconsistency., (© 2022 The Authors. Published by Elsevier Ltd.)

Background: Traditionally, hand hygiene (HH) interventions do not identify the observed healthcare workers (HWCs) and therefore, reflect HH compliance only at population level. Intensive care units (ICUs) in seven European hospitals participating in the "Prevention of Hospital Infections by Intervention and Training" (PROHIBIT) study provided individual HH compliance levels. We analysed these to understand the determinants and dynamics of individual change in relation to the overall intervention effect., Methods: We included HCWs who contributed at least two observation sessions before and after intervention. Improving, non-changing, and worsening HCWs were defined with a threshold of 20% compliance change. We used multivariable linear regression and spearman's rank correlation to estimate determinants for the individual response to the intervention and correlation to overall change. Swarm graphs visualized ICU-specific patterns., Results: In total 280 HCWs contributed 17,748 HH opportunities during 2677 observation sessions. Overall, pooled HH compliance increased from 43.1 to 58.7%. The proportion of improving HCWs ranged from 33 to 95% among ICUs. The median HH increase per improving HCW ranged from 16 to 34 percentage points. ICU wide improvement correlated significantly with both the proportion of improving HCWs (ρ = 0.82 [95% CI 0.18-0.97], and their median HH increase (ρ = 0.79 [0.08-0.97]). Multilevel regression demonstrated that individual improvement was significantly associated with nurse profession, lower activity index, higher nurse-to-patient ratio, and lower baseline compliance., Conclusions: Both the proportion of improving HCWs and their median individual improvement differed substantially among ICUs but correlated with the ICUs' overall HH improvement. With comparable overall means the range in individual HH varied considerably between some hospitals, implying different transmission risks. Greater insight into improvement dynamics might help to design more effective HH interventions in the future., (© 2022. The Author(s).)

Objectives: To evaluate the effect of a tracheal intubation safety bundle on adverse tracheal intubation-associated events across 15 PICUs., Design: Multicenter time-series study., Setting: PICUs in the United States., Patients: All patients received tracheal intubations in ICUs., Interventions: We implemented a tracheal intubation safety bundle as a quality-improvement intervention that includes: 1) quarterly site benchmark performance report and 2) airway safety checklists (preprocedure risk factor, approach, and role planning, preprocedure bedside "time-out," and immediate postprocedure debriefing). We define each quality-improvement phase as baseline (-24 to -12 mo before checklist implementation), benchmark performance reporting only (-12 to 0 mo before checklist implementation), implementation (checklist implementation start to time achieving > 80% bundle adherence), early bundle adherence (0-12 mo), and sustained (late) bundle adherence (12-24 mo). Bundle adherence was defined a priori as greater than 80% of checklist use for tracheal intubations for 3 consecutive months., Measurements and Main Results: The primary outcome was the adverse tracheal intubation-associated event, and secondary outcomes included severe tracheal intubation-associated events, multiple tracheal intubation attempts, and hypoxemia less than 80%.From January 2013 to December 2015, out of 19 participating PICUs, 15 ICUs (79%) achieved bundle adherence. Among the 15 ICUs, the adverse tracheal intubation-associated event rates were baseline phase: 217/1,241 (17.5%), benchmark reporting only phase: 257/1,750 (14.7%), early 0-12 month complete bundle compliance phase: 247/1,591 (15.5%), and late 12-24 month complete bundle compliance phase: 137/1,002 (13.7%). After adjusting for patient characteristics and clustering by site, the adverse tracheal intubation-associated event rate significantly decreased compared with baseline: benchmark: odds ratio, 0.83 (0.72-0.97; p = 0.016); early bundle: odds ratio, 0.80 (0.63-1.02; p = 0.074); and late bundle odds ratio, 0.63 (0.47-0.83; p = 0.001)., Conclusions: Effective implementation of a quality-improvement bundle was associated with a decrease in the adverse tracheal intubation-associated event that was sustained for 24 months., Competing Interests: Drs. Nishisaki, Napolitano, Shults, and Nadkarni are supported by the Agency for Healthcare Research and Quality (AHRQ R03HS021583, R18HS022464, and R18HS024511). Dr. Nadkarni is supported by the Endowed Chair in Critical Care Medicine at Children’s Hospital of Philadelphia. Dr. Napolitano’s institution received funding from AHRQ, Draeger, Aerogen, Philips/Respironics, Smiths Medical, and VERO-Biotech. Dr. Howell received funding from UptoDate. Dr. Nadkarni’s institution received funding from AHRQ R18. The remaining authors have disclosed that they do not have any conflicts of interest., (Copyright © 2020 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

We propose Neural Image Compression (NIC), a two-step method to build convolutional neural networks for gigapixel image analysis solely using weak image-level labels. First, gigapixel images are compressed using a neural network trained in an unsupervised fashion, retaining high-level information while suppressing pixel-level noise. Second, a convolutional neural network (CNN) is trained on these compressed image representations to predict image-level labels, avoiding the need for fine-grained manual annotations. We compared several encoding strategies, namely reconstruction error minimization, contrastive training and adversarial feature learning, and evaluated NIC on a synthetic task and two public histopathology datasets. We found that NIC can exploit visual cues associated with image-level labels successfully, integrating both global and local visual information. Furthermore, we visualized the regions of the input gigapixel images where the CNN attended to, and confirmed that they overlapped with annotations from human experts.

Objectives: Tracheal intubation carries a high risk of adverse events. The current literature is unclear regarding the "New Trainee Effect" on tracheal intubation safety in the PICU. We evaluated the effect of the timing of the PICU fellow academic cycle on tracheal intubation associated events. We hypothesize 1) PICUs with pediatric critical care medicine fellowship programs have more adverse tracheal intubation associated events during the first quarter (July-September) of the academic year compared with the rest of the year and 2) tracheal intubation associated event rates and first attempt success performed by pediatric critical care medicine fellows improve through the 3-year clinical fellowship., Design: Retrospective cohort study., Setting: Thirty-seven North American PICUs participating in National Emergency Airway Registry for Children., Patients: All patients who underwent tracheal intubations in the PICU from July 2013 to June 2017., Interventions: None., Measurements and Main Results: The occurrence of any tracheal intubation associated events during the first quarter of the academic year (July-September) was compared with the rest in four different types of PICUs: PICUs with fellows and residents, PICUs with fellows only, PICUs with residents only, and PICUs without trainees. For the second hypothesis, tracheal intubations by critical care medicine fellows were categorized by training level and quarter for 3 years of fellowship (i.e., July-September of 1st yr pediatric critical care medicine fellowship = first quarter, October-December of 1st yr pediatric critical care medicine fellowship = second quarter, and April-June during 3rd year = 12th quarter). A total of 9,774 tracheal intubations were reported. Seven-thousand forty-seven tracheal intubations (72%) were from PICUs with fellows and residents, 525 (5%) with fellows only, 1,201 (12%) with residents only, and 1,001 (10%) with no trainees. There was no difference in the occurrence of tracheal intubation associated events in the first quarter versus the rest of the year (all PICUs: July-September 14.9% vs October-June 15.2%; p = 0.76). There was no difference between these two periods in each type of PICUs (all p ≥ 0.19). For tracheal intubations by critical care medicine fellows (n = 3,836), tracheal intubation associated events significantly decreased over the fellowship: second quarter odds ratio 0.64 (95% CI, 0.45-0.91), third quarter odds ratio 0.58 (95% CI, 0.42-0.82), and 12th quarter odds ratio 0.40 (95% CI, 0.24-0.67) using the first quarter as reference after adjusting for patient and device characteristics. First attempt success significantly improved during fellowship: second quarter odds ratio 1.39 (95% CI, 1.04-1.85), third quarter odds ratio 1.59 (95% CI, 1.20-2.09), and 12th quarter odds ratio 2.11 (95% CI, 1.42-3.14)., Conclusions: The New Trainee Effect in tracheal intubation safety outcomes was not observed in various types of PICUs. There was a significant improvement in pediatric critical care medicine fellows' first attempt success and a significant decline in tracheal intubation associated event rates, indicating substantial skills acquisition throughout pediatric critical care medicine fellowship.

Tuberculosis (TB) is the most prevalent infectious disease in the world. In recent years there has been a significant increase in the incidence of TB due to the emergence of multidrug resistant strains of Mycobacterium tuberculosis ( M. tuberculosis ) and the increased numbers of highly susceptible immuno-compromised individuals. Central nervous system TB, includes TB meningitis (TBM-the most common presentation), intracranial tuberculomas, and spinal tuberculous arachnoiditis. Individuals with TBM have an initial phase of malaise, headache, fever, or personality change, followed by protracted headache, stroke, meningismus, vomiting, confusion, and focal neurologic findings in two to three weeks. If untreated, mental status deteriorates into stupor or coma. Delay in the treatment of TBM results in, either death or substantial neurological morbidity. This review provides latest developments in the biomedical research on TB meningitis mainly in the areas of host immune responses, pathogenesis, diagnosis, and treatment of this disease.

Stain variation is a phenomenon observed when distinct pathology laboratories stain tissue slides that exhibit similar but not identical color appearance. Due to this color shift between laboratories, convolutional neural networks (CNNs) trained with images from one lab often underperform on unseen images from the other lab. Several techniques have been proposed to reduce the generalization error, mainly grouped into two categories: stain color augmentation and stain color normalization. The former simulates a wide variety of realistic stain variations during training, producing stain-invariant CNNs. The latter aims to match training and test color distributions in order to reduce stain variation. For the first time, we compared some of these techniques and quantified their effect on CNN classification performance using a heterogeneous dataset of hematoxylin and eosin histopathology images from 4 organs and 9 pathology laboratories. Additionally, we propose a novel unsupervised method to perform stain color normalization using a neural network. Based on our experimental results, we provide practical guidelines on how to use stain color augmentation and stain color normalization in future computational pathology applications., (Copyright © 2019 Elsevier B.V. All rights reserved.)

As part of routine histological grading, for every invasive breast cancer the mitotic count is assessed by counting mitoses in the (visually selected) region with the highest proliferative activity. Because this procedure is prone to subjectivity, the present study compares visual mitotic counting with deep learning based automated mitotic counting and fully automated hotspot selection. Two cohorts were used in this study. Cohort A comprised 90 prospectively included tumors which were selected based on the mitotic frequency scores given during routine glass slide diagnostics. This pathologist additionally assessed the mitotic count in these tumors in whole slide images (WSI) within a preselected hotspot. A second observer performed the same procedures on this cohort. The preselected hotspot was generated by a convolutional neural network (CNN) trained to detect all mitotic figures in digitized hematoxylin and eosin (H&E) sections. The second cohort comprised a multicenter, retrospective TNBC cohort (n = 298), of which the mitotic count was assessed by three independent observers on glass slides. The same CNN was applied on this cohort and the absolute number of mitotic figures in the hotspot was compared to the averaged mitotic count of the observers. Baseline interobserver agreement for glass slide assessment in cohort A was good (kappa 0.689; 95% CI 0.580-0.799). Using the CNN generated hotspot in WSI, the agreement score increased to 0.814 (95% CI 0.719-0.909). Automated counting by the CNN in comparison with observers counting in the predefined hotspot region yielded an average kappa of 0.724. We conclude that manual mitotic counting is not affected by assessment modality (glass slides, WSI) and that counting mitotic figures in WSI is feasible. Using a predefined hotspot area considerably improves reproducibility. Also, fully automated assessment of mitotic score appears to be feasible without introducing additional bias or variability.