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In this paper, we explore the applications and practices that Stereolithography enables for an enhanced manufacturing process of a nitrate assay chamber for an underwater Point of Care device. Features such as engraved identifiers, creating post for inlet/outlet connections, embedding electromechanical components and optimizing the spatial distribution, were tested as a case of study for an underwater vehicle component. This study is a first approach in proposing a framework for manufacturing practices toward a new generation of customized devices for the application. The case study is validated using Computational Fluid Dynamics for the design and manufacture of an array of micromixing enhanced nitrite assay sensors that employ and exploits the enabling technology of stereolithography.

Currently, most of the students of the different Institutions of Higher Education have a social commitment, which is to develop new technologies that contribute improvements in the daily life of the people. The main objective of this proposal is to create an interface that measures the needs of the company and translates them into areas of opportunity and development for universities and to implement projects in the classroom aimed at industries and thereby bring innovations to processes, products, among others. Currently, at the Polytechnic University of Gómez Palacio, students from five different specialties are being worked on, which innovate in the creation of new products, which can be patented or implemented in the industry. Another important feature to highlight is the fact that currently there is no way to protect the authorship of students, in addition to the fact that when delivering completed projects completely, the use that will be given to these products is unknown. It is for this reason that the creation of a technology transfer center is proposed; with it, it would be promoting the innovation of projects and active participation of companies, with the support of the institution.

Patients with prurigo nodularis (PN) suffer from intractable itch and dramatic reduction in QOL. Although there is significant clinical heterogeneity in the presentation of PN, disease endotypes remain unknown. We assayed circulating plasma cytokine concentrations in patients with PN (n = 20) along with matched healthy controls and utilized an unsupervised machine learning algorithm to identify disease endotypes. We found two distinct clusters of patients with PN with noninflammatory (cluster 1) and inflammatory (cluster 2) plasma profiles. Cluster 2 had more African Americans (82%, n = 9 vs. 33%, n = 3; P = 0.028), higher Worst Itch Numeric Rating Scale scores (9.5 ± 0.9 vs. 8.3 ± 1.2; P = 0.036), and lower QOL as reflected by higher Dermatology Life Quality Index scores (21.9 ± 6.4 vs. 13.0 ± 4.1; P = 0.015). In addition, cluster 1 had a higher rate of myelopathy (67%, n = 6 vs. 18%, n = 2; P = 0.028). Compared with cluster 1, cluster 2 had higher levels of IL-1α, IL-4, IL-5, IL-6, IL-10, IL-17A, IL-22, IL-25, and IFN-α. With population-level analysis, African American patients with PN had higher erythrocyte sedimentation rate, C-reactive protein, ferritin, and eosinophils and lower transferrin than Caucasian patients with PN. These findings indicate discrete clusters of patients with PN with plasma biomarker profiles corresponding to distinct demographic and clinical characteristics, potentially allowing for precision medicine approaches to treat PN.

Background: Palliative care (PC) for patients with malignant hematological diseases is scarcely documented, particularly in low- and middle-income countries. This study aimed to document PC provided to patients with hematologic malignancies. Methods: Bidirectional study conducted from July 2016 to June 2019 at the hematology and palliative care departments at a reference center in Northeast Mexico for low-income open population uninsured patients. Clinical records and electronic files of patients with malignant hematological diseases of both sexes and all ages attending an academic hematology center were reviewed. Statistical analysis was performed with the SPSS version 22 program. Acute and chronic leukemias, multiple myeloma, Hodgkin lymphoma, non-Hodgkin lymphoma, and others were included. Results: Five-hundred ten patients were studied, of which 148 (29%) died. Eighty-one (15.88%) patients including 31 (20.9%) who died received PC. Median age at palliative diagnosis was 42 (2-91) years. The most common symptom was pain (69.7%). The most frequent reason for palliative referral was treatment-refractory disease (39%). During the last week of life, 19 (95%) of 20 patients had blood sampling; 17 (85%) received antibiotics; 16 (80%) had a urinalysis performed; 16 (80%) received analgesia, including paracetamol (11, 35.5%) and buprenorphine (7, 22.6%); 10 (50%) received blood products; 9 (45%) were intubated; and central venous catheters were inserted in 5 (25%) patients. Conclusions: Palliative care was provided to a minority of patients with hematologic malignancies and considerable improvement is required in its timely use and extension.

BACKGROUND: The efficacy of antibiotics in rosacea treatment suggests a role for microorganisms in its pathophysiology. Growing concern over the adverse effects of antibiotic use presents a need for targeted antimicrobial treatment in rosacea. OBJECTIVE: We performed a case–control study to investigate the skin microbiota in patients with rosacea compared to controls matched by age, sex, and race. METHODS: Nineteen participants with rosacea, erythematotelangiectatic, papulopustular, or both, were matched to 19 rosacea-free controls. DNA was extracted from skin swabs of the nose and bilateral cheeks of participants. Sequencing of the V3V4 region of the bacterial 16S ribosomal RNA gene was performed using Illumina MiSeq and analyzed using QIIME/MetaStats 2.0 software. RESULTS: Compared with controls, skin microbiota in erythematotelangiectatic rosacea was depleted in Roseomonas mucosa (p = 0.004). Papulopustular rosacea was enriched in Campylobacter ureolyticus (p = 0.001), Corynebacterium kroppenstedtii (p = 0.008), and the oral flora Prevotella intermedia (p = 0.001). The highest relative abundance of C. kroppenstedtii was observed in patients with both erythematotelangiectatic and papulopustular rosacea (19.2%), followed by papulopustular (5.06%) and erythematotelangiectatic (1.21%) rosacea. C. kroppenstedtii was also associated with more extensive disease, with the highest relative abundance in rosacea affecting both the cheeks and nose (2.82%), followed by rosacea sparing the nose (1.93%), and controls (0.19%). CONCLUSIONS: The skin microbiota in individuals with rosacea displays changes from that of healthy skin, suggesting that further studies examining a potential role for the skin microbiota in the pathophysiology of rosacea may be warranted.

IgE induced by type 2 immune responses in atopic dermatitis is implicated in the progression of atopic dermatitis to other allergic diseases, including food allergies, allergic rhinitis, and asthma. However, the keratinocyte-derived signals that promote IgE and ensuing allergic diseases remain unclear. Herein, in a mouse model of atopic dermatitis-like skin inflammation induced by epicutaneous Staphylococcus aureus exposure, keratinocyte release of IL‑36α along with IL-4 triggered B cell IgE class-switching, plasma cell differentiation, and increased serum IgE levels-all of which were abrogated in IL-36R-deficient mice or anti-IL‑36R-blocking antibody-treated mice. Moreover, skin allergen sensitization during S. aureus epicutaneous exposure-induced IL-36 responses was required for the development of allergen-specific lung inflammation. In translating these findings, elevated IL‑36 cytokines in human atopic dermatitis skin and in IL‑36 receptor antagonist-deficiency patients coincided with increased serum IgE levels. Collectively, keratinocyte-initiated IL‑36 responses represent a key mechanism and potential therapeutic target against allergic diseases.

Importance The ability to predict the efficacy of systemic psoriasis therapy based on immune profiles in skin biopsies could reduce the use of inappropriate treatment and its associated costs and adverse events. It could considerably decrease drug development trial costs as well. Objective To develop a bioinformatic gene signature score derived from skin mRNA to predict psoriasis treatment outcomes for a variety of therapies. Design, Setting, and Participants In this decision analytical model using 1145 skin samples from different cohorts of 12 retrospective psoriasis studies, samples were analyzed using the CIBERSORT algorithm to define the immune landscape of psoriasis lesions and controls. Random forest classification and principal component analysis algorithms were used to estimate psoriatic microenvironment (PME) signature genes and construct a PME score. Overall, 85 and 421 psoriasis lesions from 1 and 4 independent cohorts were used as discovery and validation studies, respectively. Among them, 157, 71, 89, and 90 psoriasis lesions were treated with etanercept, tofacitinib, adalimumab, and methotrexate, respectively. Main Outcomes and Measures Number of weeks after treatment initiation when responders and nonresponders could be predicted. Results Overall, 22 immune cell subtypes formed infiltration patterns that differentiated psoriasis lesions from healthy skin. In psoriasis lesions, the expression of 33 PME signature genes defined 2 immune phenotypes and in aggregate could be simplified to a numerical PME score. A high PME score, characterized by keratinocyte differentiation, correlated with a better treatment response (Psoriasis Area and Severity Index [PASI] reduction, 75.8%; 95% CI, 69.4% to 82.2%;P = .03), whereas a low PME score exhibited an immune activation signature and was associated with a worse response (PASI reduction, 53.5%; 95% CI, 45.3% to 61.7%;P = .03). The PME score at week 4 after treatment initiation correlated with future responder vs nonresponder to treatment status 8 to 12 weeks earlier than PASI reduction for etanercept, methotrexate plus adalimumab, and tofacitinib. Conclusions and Relevance The PME score is a biometric score that may predict clinical efficacy of systemic psoriasis therapy in advance of clinical responses. As an application of personalized medicine, it may reduce the exposure of patients with psoriasis to ineffective and expensive therapies.

Relapse and graft failure after autologous (auto) or allogeneic (allo) hematopoietic stem cell transplantation (HSCT) are serious and frequently fatal events. A second HSCT can be a life-saving alternative, however, information on the results of such intervention in an outpatient setting is limited. Outpatient second hematoprogenitors transplant after reduced-intensity conditioning (RIC) at a single academic center was analyzed. Twenty-seven consecutive adults who received an allo-HSCT after an initial auto- or allo-HSCT from 2006 to 2019 were included. Data were compared using the χ2 -test. Survival analysis using Kaplan-Meier and Cox proportional hazard models was performed; cumulative incidence estimation of transplant-related mortality (TRM) was assessed. Hodgkin lymphoma was the most frequent diagnosis for the group with a first auto-HSCT with 5/12 (41.7%) cases, and acute myeloid leukemia for those with a first allo-HSCT with 6/15 (40%). One-year overall survival and disease-free survival (DFS) was 66.7% (95% CI 27.2-88.2) and 59% (95% CI 16-86) for 12 patients with a first auto-HSCT; and for 15 patients with a first allo-HSCT, it was 43.3% (95% CI 17.9-66.5) and 36% (95% CI 13.2-59.9), respectively. Eight (29.6%) patients died of TRM and the cumulative incidence of TRM at 1 year was 22% (95% CI 8.6-39.27). Chronic graft-versus-host disease and late (>10 months) second transplantation were protective factors for longer survival. Neutropenic fever was more common in the group with a first allo-HSCT (p = 0.01). In conclusion, outpatient second allo-HSCT using RIC after auto- or allografting failure or relapse is feasible and offers a reasonable alternative for patients with severe life-threatening hematological diseases.

Efficacy of an ambulatory hematopoietic stem cell transplant (HSCT) program with a reduced intensity conditioning regimen (RIC) in malignant hematological diseases was assessed. We analyzed 217 patients who underwent HSCT from August 2013 to July 2017. There were 78 (35.9%) HLA-identical, 56 (25.8%) haploidentical, and 83 (38.2%) autologous transplants. Two-year transplant-related mortality (TRM) for HLA-identical, haploidentical, and auto grafts were 20%, 25%, and 2.5%; relapse/progression was 44%, 60%, and 55%; overall survival (OS) was 61%, 44.8%, and 78.0%; and disease-free survival (DFS) was 36.8%, 26.5%, and 43.5%, respectively. Factors associated with a high risk of TRM were male sex (HR = 2.62, P = 0.031), fever and neutropenia (HR = 3.30, P = 0.023), and cell dose

Introduction The outcomes for adolescents and young adults (AYAs) with acute myeloid leukemia (AML) have been poorly characterized in Hispanics in low- to middle-income countries. The results are influenced by biologic and socioeconomic factors. The clinical paths for AYA patients with AML are reported. Patients and Methods A retrospective analysis of AYA and pediatric AML patients aged 1 to 39 years during 2003 to 2016 from a single reference center in Northeast Mexico treated with a 7+3 standard protocol was performed. The 5-year overall survival (OS) and event-free survival (EFS) were estimated using Kaplan-Meier analysis. The hazard ratios for relapse and death were estimated using a Cox regression model. The patients with promyelocytic leukemia were analyzed separately. Results The study included 110 non-PML AML patients, 39 children and 71 AYAs. No difference in complete remission was found ( P = .446), although the overall response rate was greater in the children (87.2% vs. 69% in AYAs; P = .034). The 5-year EFS rate was 33% for the children versus 9.3% in the AYAs at a median follow-up of 22 and 9 months, respectively ( P = .008). The 5-year OS rate was 51% in the children and 22% in the AYAs ( P = .001). Of the 44 AYAs with complete remission, 29 (65%) developed a relapse. Of the 39 children and 71 AYAs, 20 children (51.3%) and 21 AYAs (29.6%) underwent transplantation ( P = .024). Patients with refractory disease had a 1-year OS rate of 14.4%. Older age (hazard ratio [HR], 2.55; P = .002) and white blood cell count > 50 × 10 9 /L (HR, 1.79; P = .023) were significant for death, and transplantation was protective (HR, 0.57; P = .023). Conclusion Low EFS and OS rates were found for AML patients in the AYA group. To improve survival rates, intensified chemotherapy regimens and early hematopoietic stem cell transplantation are needed.

Prurigo nodularis is an understudied, chronic inflammatory skin disease that disproportionately affects African-Americans and presents with intensely pruritic nodules of unknown etiology. To better characterize immune dysregulation in prurigo nodularis, peripheral blood mononuclear cells and skin biopsies were obtained from majority African American patients with prurigo nodularis and healthy subjects matched by age, race, and sex. Flow cytometric analysis of functional T-cell response comparing prurigo nodularis to healthy subjects identified increased γδT-cells (CD3(+)CD4(−)CD8(−)γδTCR(+)) with Vδ2(+) γδT-enrichment. Activated T-cells demonstrated uniquely increased IL-22 cytokine expression in prurigo nodularis patients when compared to healthy controls. CD4+ and CD8+ T-cells were identified as the source of increased circulating IL-22. Consistent with these findings, RNA-sequencing of lesional prurigo nodularis skin compared to non-lesional prurigo nodularis skin and biopsy site matched control skin demonstrated robust up-regulation of Th22-related genes and signaling networks implicated in impaired epidermal differentiation. Th22-related cytokine upregulation remained significant with stratifications by race and biopsy site. Importantly, the expression of the IL-22 receptors IL22RA1/A2 was significantly elevated in lesional prurigo nodularis skin. These results indicate both systemic and cutaneous immune responses in prurigo nodularis patients are skewed towards a Th22/IL-22 profile. Prurigo nodularis may benefit from immunomodulatory therapies directed at Th22-mediated inflammation.

Purpose: Keloid is a disease that affects millions of patients and has relatively few effective treatment options. Unfortunately, traditional 2D monolayer culture of keloid derived fibroblasts show little resemblance to the pathological process in vivo. Additionally, keloid is notably a pathology largely specific to humans, without good in vivo models available. To fill this gap, we have developed a 3D in vitro microtissue keloid scar model with human keloid derived fibroblasts and peripheral blood derived macrophages. Methods: Under IRB approval, keloid tissue was from patients and used to develop a human keloid derived fibroblast line. Keloid spheroids were fabricated from these keloid derived fibroblasts and human peripheral blood derived macrophages. Commercial human skin-derived fibroblast and 2D monolayers were used as controls. Quantitative PCR with fibrosis genes (collagen-1, aSMA, TNF, IL1β, IL6 and TGFβ) and immunofluorescent staining with (collagen-1, aSMA, CD68 and pSTAT3 were performed to validate the keloid spheroids as an effective keloid model in vitro. In addition, we performed qPCR fibrosis microarray for fibrosis-specific gene expression. Lastly, the Affymetrix PrimeView array was used to evaluate genome-wide comprehensive gene expression to assess whether the keloid spheroid mimicking behavior of keloid tissue regarding gene expression level. Results: Spheroids had significantly higher expression levels of all fibrosis related genes compared to the 2D monolayer control. Among the spheroid groups, keloid spheroids had much higher gene expression levels of collagen-1 and aSMA, which was confirmed by the immunofluorescent staining with the same correspondence proteins. Interestingly, keloid spheroids showed lower gene expression levels of common fibrosis related cytokines (TNF, IL1β, IL6 and TGFβ). However, IF of pSTAT3 was upregulated in keloid spheroid, which is consistent with previous literature of keloid research. Lastly, qPCR fibrosis array and human comprehensive gene expression assay validated the result of qPCR and indicated that macrophages in the keloid spheroids showed signs of polarization in both M1 and M2 directions. Conclusions: We have developed a keloid mimicking spheroid microtissue as a more physiologically relevant in vitro keloid model for drug development and research exploring gene and protein expression pathways. This platform recapitulates important features of keloid behavior not seen in 2D culture. Future work will include screening of keloid spheroid responses to potential therapeutic treatments.

Background: Heterogeneity regarding clinical and laboratory findings at diagnosis of acute lymphoblastic leukemia exists. The frequency of complete blood count abnormalities and its combinations, symptoms and physical findings were investigated in Hispanic children from an open population at the diagnosis of acute lymphoblastic leukemia. Methods: The patient charts and electronic records of under 16-year-old children diagnosed with acute lymphoblastic leukemia over 10 years at a regional hematology center of a university hospital were analyzed to retrieve data concerning the complete blood count at first evaluation. Type and distribution of abnormal data, frequency of symptoms and physical findings at presentation were documented. Results: The records of 203 children aged 0–15 years diagnosed with acute lymphoblastic leukemia from 2006 to 2016 were revisited. The results of the blood workup showed a median white blood cell count of 7120 × 109/L (range: 450–600,000 × 109/L), and a median hemoglobin concentration of 7.5 g/dL (range: 2.4–15.3 g/dL), whereas the median platelet count was 47,400 × 109/L (range: 4000–544,000 × 109/L). Leukocytosis and leukopenia were present in 36.6% and 36.1% of cases, respectively; anemia was diagnosed in 82.9% children. The order of frequency for major clinical symptoms was fatigue 62%, fever 60%, bone and joint pain 39%, hyporexia 33% and weight loss 21%, while main physical findings were hepatomegaly 78%, splenomegaly 63%, lymphadenopathy 57%, pallor 48%, and purpura 30%. Conclusion: Data differing from those classically expected at diagnosis of acute lymphoblastic leukemia in children were documented in a cohort of Hispanic children over one decade with a wide spectrum of complete blood count abnormalities, forms of presentation and frequency of physical findings. Keywords: Acute lymphoblastic leukemia, Complete blood count, Leukocytosis, Hepatomegaly, Splenomegaly

Given the widespread use of systemic antibiotics for treatment of moderate to severe acne, it is important to understand the associations of such antibiotic use with changes not only in Cutibacterium acnes (formerly Propionibacterium acnes) but also in the complete bacterial community of the skin.To examine the composition, diversity, and resilience of skin microbiota associated with systemic antibiotic perturbation in individuals with acne.This longitudinal cohort study conducted at an academic referral center in Maryland from February 11 to September 23, 2014, included 4 female participants who had received a recent diagnosis of acne vulgaris, showed comedonal and inflammatory acne on the face, were at least 18 years old, and had no recent use of systemic or topical treatments for acne, including antibiotics and retinoids. Data analysis was performed between July 5, 2017, and November 7, 2018.Participants were prescribed oral minocycline, 100 mg, twice daily for 4 weeks. Skin areas on the forehead, cheek, and chin were sampled for 16S ribosomal RNA gene sequencing at baseline, 4 weeks after starting minocycline treatment, and then 1 week and 8 weeks after discontinuation of treatment.Skin microbiota examined with respect to relative abundance of bacterial taxa, α diversity (represents within-sample microbial diversity), and β diversity (represents between-sample microbial diversity). Acne status evaluated with photography and lesion count.Of the 4 patients included in this study, 2 were 25 years old, 1 was 29 years old, and 1 was 35 years old; 2 were white women, 1 was an African American woman, and 1 was an Asian woman. Across all 4 patients, antibiotic treatment was associated with a 1.4-fold reduction in the level of C acnes (difference, -10.3%; 95% CI, -19.9% to -0.7%; P = .04) with recovery following cessation of treatment. Distinct patterns of change were identified in multiple bacterial genera, including a transient 5.6-fold increase in the relative abundance of Pseudomonas species (difference, 2.2%; 95% CI, 0.9%-3.4%; P .001) immediately following antibiotic treatment, as well as a persistent 1.7-fold increase in the relative abundance of Streptococcus species (difference, 5.4%; 95% CI, 0.3%-10.6%; P = .04) and a 4.7-fold decrease in the relative abundance of Lactobacillus species (difference, -0.8%; 95% CI, -1.4% to -0.2%; P = .02) 8 weeks following antibiotic treatment withdrawal. In general, antibiotic administration was associated with an initial decrease from baseline of bacterial diversity followed by recovery. Principal coordinates analysis results showed moderate clustering of samples by patient (analysis of similarity, R = 0.424; P = .001) and significant clustering of samples by time in one participant (analysis of similarity, R = 0.733; P = .001).In this study, systemic antibiotic treatment of acne was associated with changes in the composition and diversity of skin microbiota, with variable rates of recovery across individual patients and parallel changes in specific bacterial populations. Understanding the association between systemic antibiotic use and skin microbiota may help clinicians decrease the likelihood of skin comorbidities related to microbial dysbiosis.

This paper presents a methodology on the design of an optimal predictive control scheme applied to an islanded microgrid. The controller manages the batteries energy and performs a centralized load shedding strategy to balance the load and generation within the microgrid, and to keep the stability of the voltage magnitude. A nonlinear model predictive control (NMPC) algorithm is used for processing a data set composed of the batteries state of charge, the distributed energy resources (DERs) active power generation, and the forecasted load. The NMPC identifies upcoming active power unbalances and initiates automated load shedding over noncritical loads. The control strategy is tested in a medium voltage distribution system with DERs. This control strategy is assisted by a distribution monitoring system, which performs real-time monitoring of the active power generated by the DERs and the current load demand at each node of the microgrid. Significant performance improvement is achieved with the use of this control strategy over tested cases without its use. The balance between the power generated by the DERs and the load demand is maintained, while the voltage magnitude is kept within the maximum variation margin of $\pm 5\%$ recommended by the standard ANSI C84.1-1989.

Background Central centrifugal cicatricial alopecia (CCCA) is a primary cicatricial alopecia that most commonly affects women of African descent. Like CCCA, fibroproliferative disorders (FPDs) such as keloids, atherosclerosis, and fibroids are characterized by low-grade inflammation and irritation, resulting in end-stage fibrosis. Objective We sought to determine whether fibroproliferative genes were up-regulated in patients with CCCA. Methods A total of 5 patients with biopsy-proven CCCA were recruited for this study. Two scalp biopsy specimens were obtained from each patient; 1 from CCCA-affected vertex scalp and 1 from the unaffected occipital scalp. Microarray analysis was performed to determine the differential gene expression patterns. Results There was an upregulation of genes implicated in FPDs in patients with CCCA. Specifically, we noted increased expression of platelet derived growth factor gene (PDGF), collagen I gene (COL I), collagen III gene (COL III), matrix metallopeptidase 1 gene (MMP1), matrix metallopeptidase 2 gene (MMP2), matrix metallopeptidase 7 gene (MMP7), and matrix metallopeptidase 9 gene (MMP9) in affected scalp compared with in unaffected scalp. Significant overlap in the canonic pathways was noted between patients with CCCA and patients with both atherosclerosis and hepatic fibrosis (P Limitations Small sample size and the use of whole skin tissue for analysis. Conclusion We have identified the upregulation of critical genes implicated in FPDs in the gene expression profile of patients with CCCA. These findings may help identify future therapeutic targets for this otherwise difficult-to-treat condition.

In this paper, a sensor placement approach to improve the leak location in water distribution networks is proposed when the leak signature space (LSS) method is used. The sensor placement problem is formulated as an integer optimization problem where the criterion to be minimized is the number of overlapping signature domains computed from the original LSS representation. First, a semi-exhaustive search approach based on a lazy evaluation mechanism ensures optimal placement in the case of low complexity scenarios. For more complex cases, a stochastic optimization process is proposed, based on either the genetic algorithms (GAs) or particle swarm optimization (PSO). Experiments on two different networks are used to evaluate the performance of the resolution methods, as well as the efficiency achieved in the leak location when using the sensor placement results.

BACKGROUND: The shave biopsy using a razor with an open blade is the current standard of care for sampling superficial skin lesions. OBJECTIVE: To enhance safety, the authors developed a novel biopsy device with a closed blade design for removing the epidermal layer of skin and evaluated against the open razor blade for tolerability, scarring, and accuracy in histological diagnosis. MATERIALS AND METHODS: Shave biopsies were performed using the novel device or razor blade on benign epidermal skin lesions in 10 patients on comparable body parts. Digital photography, colorimetry, scar scale evaluations, and questionnaires were used to evaluate the efficacy and tolerability of the devices. RESULTS: For all patients, accurate histological diagnoses were made regardless of device type. No statistically significant differences were detected between the novel device and razor blade in terms of scar scale assessments, colorimetry, and questionnaire responses. Both patients and the participating dermatologist reported satisfaction with the safety and performance of the novel device. No injuries to the provider occurred with either instrument. CONCLUSION: The rotating sphere biopsy device is a potential alternative to the razor blade with comparable tolerability, scarring, and accuracy in histological diagnoses, offering improved safety for patients and health care providers.

Background and Objective. Hematopoietic stem cell transplantation (HSCT) in developing countries is cost-limited. Our primarygoalwastodeterminethecoststructurefortheHSCT program model developed over the last decade at our public university hospital and to assess its clinical outcomes. Materials and Methods. Adults and children receiving an allogeneic hematopoietic stem cell transplant from January 2010 to February 2011 at our hematology regional reference center were included. Laboratory tests, medical procedures, chemotherapy drugs, other drugs, and hospitalization costs were scrutinized to calculate the total cost for each patient and the median cost for the procedure. Data regarding clinical evolution were incorporated into the analysis. Physician fees are not charged at the institution and therefore were not included. Results. Fiftypatientswereevaluatedovera1-yearperiod.The total estimated cost for an allogeneic HSCT was $12,504.The two most expensive diseases to allograft were non-Hodgkin lymphoma ($11,760 6 $2,236) for the malignant group and thalassemia ($12,915 6 $5,170) for the nonmalignant group. Acute lymphoblastic leukemia ($11,053 6 2,817) and acute myeloblastic leukemia ($10,251 6 $1,538) were the most frequentindicationsforHSCT,with11caseseach.Medianoutof-pocket expenses were $1,605, and 1-year follow-up costs amounted to $1,640, adding up to a total cost of $15,749 for thefirstyear.Themostexpensivecomponentsweredrugsand laboratory tests. Conclusion. Applying the cost structure described, HSCT is an affordable option for hematological patients living in a developing country.The Oncologist 2015;20:386–392 Implications for Practice: This article describes in detail the strategy for performing hematologic transplantation at a public institution caring for uninsured patients applying an in-house cost-efficiency model that maximizes scarce financial resources. It provides individual costs for standard drugs and therapeutic, as well as laboratory, procedures used during the intervention. The results are important because they convey the message that this type of transplant can be made at affordable costs for diverse hematologic diseases without requiring expensive infrastructure,exemplifying how good clinical results, similar to those in advanced institutions in developed countries, can be reached with adequate planning and an experienced team.

In this paper, a sensor placement approach to improve the leak location in water distribution networks is proposed. The sensor placement problem is formulated as an integer optimization problem where the criterion to minimize is the number of overlapping signature domains computed from the leak signature space (LSS) representation. A stochastic optimization process is proposed to solve this problem, based on either a Genetic Algorithms (GA) or a Particle Swarm Optimization (PSO) approach. Experiments on two different DMAs are used to evaluate the performance of the resolution methods as well as the efficiency achieved in the leak location when using the sensor placement results.

The relationship between treatment for hematologic malignancies and risk of developing metabolic syndrome (MS) is controversial; in addition, metabolic changes following hematopoietic stem cell transplantation (HSCT) is an area of growing interest. We documented the presence of MS in patients with hematological malignancies treated with chemotherapy and HSCT. Nutritional status, anthropometrics, and pertinent laboratory parameters were used to evaluate the presence of MS using the Adult Treatment Panel (ATP III) criteria. In the study, 115 patients were included. Using ATP III criteria, MS was identified in 42 (44.7%) patients treated only with chemotherapy and in 8 (33.3%) patients with an HSCT. There was an important but not significant difference in the mean fasting glucose, which was higher in the chemotherapy group (108.32 ± 54.28 vs. 94.48 ± 18.25, P = 0.300). Mean values of biochemical markers and blood pressure were not different between the groups. An increase in central obesity in men with hematological diseases in comparison to the rest of the population was also found (46.7% vs 32.4%). There was no difference in the prevalence of MS between patients with hematologic malignancies receiving an HSCT and those treated with chemotherapy alone.

Summary This paper presents new design methodology and performance comparison of two hybrid fault-tolerant control (FTC) schemes applied to the regulation of the frequency and voltage amplitude of a diesel engine generator installed in a microgrid. Both of them are based on a unique combination of a model reference adaptive control (MRAC) with a proportional-integral-derivative (PID) controller and artificial intelligence techniques, i.e. artificial neural networks (ANN) and genetic algorithms (GA). Since in an islanded microgrid, the frequency of the system is determined by the shaft speed of the diesel engine (DE), while the voltage amplitude is set by the synchronous generator (SG) field voltage, therefore, two FTC systems for frequency and voltage regulation have been implemented in each proposed control scheme. The first scheme consists of an MRAC system with a PID controller tuned by a GA for controlling the speed of the DE and a classic MRAC system for controlling the voltage amplitude of the SG. In the second scheme, an MRAC system with a GA-tuned PID controller is used for the DE, and a hybrid controller in which the MRAC is combined with an ANN and a PID controller tuned by a GA is designed for the SG. The dynamic models of the microgrid components are presented in detail, and the proposed microgrid and its FTC systems are implemented and tested in the Simpower Systems of MATLAB/Simulink® simulation environment. All results indicate high effectiveness and robustness of the MRAC-based FTC schemes in both normal and emergency/faulty operations of the microgrid in comparison with a benchmark baseline controller, IEEE Type 1 AVR for the SG and a PID controlled governor for the DE. Copyright © 2014 John Wiley & Sons, Ltd.

Background/Objective: Acute myeloid leukemia (AML) is the most common acute leukemia in adults. We documented the characteristics and results of treatment of patients with AML at a single reference center. Methods: Patients diagnosed with AML between June 2003 and July 2011 at a university hospital in northeast Mexico were studied. Overall survival (OS) and event-free survival (EFS) were determined, and risk factors were analyzed with respect to their influence on prognosis. Results: A total of 132 AML patients were included. Median age was 32 years. Complete remission (CR) was achieved by 55% of patients. CR was achieved by 65.1% of patients 60 years (n = 23; p < 0.001). In all, 39% of patients >60 years suffered an early death, compared to 14.7% of those 60 years had a lower OS and EFS (p < 0.001). A total of 28% of patients received a transplant, and they had higher OS and EFS. Conclusions: Our patients were considerably younger and had remarkably lower survival rates than reported for other populations; those >60 years had a higher early death rate, and fewer of these patients achieved CR.

Background Atopic dermatitis (AD) is associated with epidermal barrier defects, dysbiosis, and skin injury caused by scratching. In particular, the barrier-defective epidermis in patients with AD with loss-of-function filaggrin mutations has increased IL-1α and IL-1β levels, but the mechanisms by which IL-1α, IL-1β, or both are induced and whether they contribute to the aberrant skin inflammation in patients with AD is unknown. Objective We sought to determine the mechanisms through which skin injury, dysbiosis, and increased epidermal IL-1α and IL-1β levels contribute to development of skin inflammation in a mouse model of injury-induced skin inflammation in filaggrin-deficient mice without the matted mutation (ft/ft mice). Methods Skin injury of wild-type, ft/ft, and myeloid differentiation primary response gene–88–deficient ft/ft mice was performed, and ensuing skin inflammation was evaluated by using digital photography, histologic analysis, and flow cytometry. IL-1α and IL-1β protein expression was measured by means of ELISA and visualized by using immunofluorescence and immunoelectron microscopy. Composition of the skin microbiome was determined by using 16S rDNA sequencing. Results Skin injury of ft/ft mice induced chronic skin inflammation involving dysbiosis-driven intracellular IL-1α release from keratinocytes. IL-1α was necessary and sufficient for skin inflammation in vivo and secreted from keratinocytes by various stimuli in vitro. Topical antibiotics or cohousing of ft/ft mice with unaffected wild-type mice to alter or intermix skin microbiota, respectively, resolved the skin inflammation and restored keratinocyte intracellular IL-1α localization. Conclusions Taken together, skin injury, dysbiosis, and filaggrin deficiency triggered keratinocyte intracellular IL-1α release that was sufficient to drive chronic skin inflammation, which has implications for AD pathogenesis and potential therapeutic targets.

Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) has been developed as an alternative transplant strategy for children with hematological disorders who do not have an HLA-matched donor. We report the analysis of the outcome for 18 consecutive pediatric patients with various hematological diseases, who underwent haplo-HSCT using a reduced-intensity conditioning regimen and CD3/CD19 depletion in an outpatient setting. Twelve of the 18 patients (66.6%) engrafted either transiently or definitively (9 patients engrafted with full donor chimerism and 3 with mixed chimerism). Six patients with acute lymphoblastic leukemia were disease-free between 2 and 35 months (median 25 months) post-HSCT. The overall survival was 33.3% with a median of 25 months (range 2-35). Our results suggest that haplo-HSCT can be a feasible therapeutic alternative for children who do not have a suitable family donor or available cord blood units. These results also demonstrate that it is possible to perform this regimen on an outpatient basis.

This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license., This paper proposes a new sensor placement approach for leak location in water distribution networks (WDNs). The sensor placement problem is formulated as an integer optimization problem. The optimization criterion consists in minimizing the number of non-isolable leaks according to the isolability criteria introduced. Because of the large size and non-linear integer nature of the resulting optimization problem, genetic algorithms (GAs) are used as the solution approach. The obtained results are compared with a semi-exhaustive search method with higher computational effort, proving that GA allows one to find near-optimal solutions with less computational load. Moreover, three ways of increasing the robustness of the GA-based sensor placement method have been proposed using a time horizon analysis, a distance-based scoring and considering different leaks sizes. A great advantage of the proposed methodology is that it does not depend on the isolation method chosen by the user, as long as it is based on leak sensitivity analysis. Experiments in two networks allow us to evaluate the performance of the proposed approach. © 2013 by the authors; licensee MDPI, Basel, Switzerland., This work is supported by the Research Chair in Supervision and Advanced Control of Tecnológico de Monterrey, Campus Monterrey and by a CONACYT studentship. This work has been partially grant-funded by CICYTSHERECSDPI-2011-26243 and CICYT WATMANDPI-2009-13744 of the Spanish Ministry of Education, by iSense grant FP7-ICT-2009-6-270428 and by EFFINETgrant FP7-ICT-2012-318556 of the European Commission. This work is also partially founded by the Fond National de la Recherche, Luxembourg (CO11/IS/1206050).

Background The impact of obesity on hematopoietic stem cell transplantation (HSCT) outcome remains controversial and has been considered a relative contraindication for the procedure. We investigated the influence of Body Mass Index (BMI) on the clinical course of adults undergoing an ambulatory HSCT after a non-myeloablative conditioning regimen. Methods Adults with hematologic diseases undergoing an autologous or allogeneic HSCT after reduced intensity conditioning (RIC) and supported exclusively with enteral nutrition (EN) were studied. BMI and body fat were sequentially determined. Patients were divided into three BMI subgroups: underweight; normal, and overweight/obese. Results Seventy-seven patients with a median follow-up of 21 months were evaluated. Fourteen (18.2%) were underweight, 21 (27.3%) had a normal weight, and 42 (54.5%) were overweight/obese. A significant weight loss was observed among all three weight groups after HSCT ( P = 0.014). No correlation was found between time to engraftment and BMI ( P = 0.91), serum albumin ( P = 0.387), and fasting glucose ( P = 0.64), nor between BMI and acute ( P = 0.456) or chronic ( P = 0.209) graft versus host disease (GVHD). On multivariate analysis a higher overall survival (OS) was documented for obese patients ( P = 0.037). Discussion A BMI > 30/kg/m 2 was independently associated with a higher survival rate after HSCT. Obese patients should not be excluded as transplant candidates based only on this parameter.

Monitoring of electric power systems is particularly challenging due to the presence of dynamic load changes of network nodes, as well as the presence of both continuous and discrete variables, noisy information and lack of data. The need to develop more powerful approaches has been recognized, and hybrid techniques that combine several reasoning methods start to be used. A fault diagnosis framework that is able to locate the set of nodes involved in multiple fault events is proposed. A methodology based on the system history data combining an AutoAssociative Neural Network (AANN) and Adaptive Neuro-Fuzzy Inference Systems (ANFIS) detects faulty nodes, type of faults and time when the faults appear.

This paper presents a comparison of two different adaptive control schemes for improving the performance of a hybrid wind-diesel power system in an islanded microgrid configuration against the baseline controller, IEEE type 1 automatic voltage regulator (AVR). The first scheme uses a model reference adaptive controller (MRAC) with a proportional-integral-derivative (PID) controller tuned by a genetic algorithm (GA) to control the speed of the diesel engine (DE) for regulating the frequency of the power system and uses a classical MRAC for controlling the voltage amplitude of the synchronous machine (SM). The second scheme uses a MRAC with a PID controller tuned by a GA to control the speed of the DE, and a MRAC with an artificial neural network (ANN) and a PID controller tuned by a GA for controlling the voltage amplitude of the SM. Different operating conditions of the microgrid and fault scenarios in the diesel engine generator (DEG) were tested: 1) decrease in the performance of the diesel engine actuator (40% and 80%), 2) sudden connection of 0.5 MW load, and 3) a 3-phase fault with duration of 0.5seconds. Dynamic models of the microgrid components are presented in detail and the proposed microgrid and its fault-tolerant control (FTC) are implemented and tested in the Simpower Systems of MATLAB/Simulink® simulation environment. The simulation results showed that the use of ANNs in combination with model-based adaptive controllers improves the FTC system performance in comparison with the baseline controller.

An adaptive predictive ( AP ) control strategy for a multi-input multi-output (MIMO) industrial process is designed. The Relative Gain Array pairing technique is used to define the adaptive predictive control strategy, i.e. the AP models structure. The control strategy is simulated using the ADEX. The controllers' performance is evaluated on a simulator of a crude oil atmospheric distillation process which is currently operating in a Petroleos Mexicanos refinery. The simulation results are also compared with a PID-based control strategy, showing an improvement of operation stability.

The climatic chambers are enclosures that provide a desired climate regardless of the outside environment. They are frequently used in research and industry, durability testing of materials, devices or appliances. FIME-UANL developed a climatic chamber, it is located in the climate-controlled laboratory. This climatic chamber has the facility of electronic expansion valve (EEV), electronic hot gas valve bypass (EHGB), pressure regulating valve (EPR). The goal of this work is to develop and implement control algorithms, that to improve the performance of the cooling system of the climatic chamber without compromising its performance in terms of accuracy and stability. In addition to assessing the energy performance through the pressure ratio due to the use of control strategies in the cooling system of the climatic chamber using cooling system COP and pressure ratio as a comparator.

Background The therapeutic progress for adults with acute lymphoblastic leukemia (ALL) has been slow, with a 5-year survival of 30% to 45% in developed countries. Scarce information is available regarding the treatment and survival rates from nonindustrialized populations. In the present study, the characteristics of adults with ALL at a single institution were documented. Patients and Methods The clinical files of patients aged ≥ 18 years who had been diagnosed with ALL from 2005 to 2015 at a reference center in Mexico were scrutinized. Overall survival (OS) and event-free survival (EFS) were determined using the Kaplan-Meier method. The hazard ratios for death and relapse were estimated using Cox regression analysis. Results A total of 94 adults were included. Their median age was 33 years; 69 (73.4%) had high-risk and 25 (26.6%) had standard-risk ALL. Of the 94 patients, 67 (71.3%) achieved complete remission (CR), 20 (21.3%) experienced disease resistance, and 7 (7.4%) died early during induction to remission, mainly of sepsis. The 5-year EFS and OS was 23.4% and 31.1% for the whole group and 24.9% and 38.9% for patients who achieved CR, respectively. Of the 94 patients, 50 (43.9%) died of sepsis or disease progression. Relapse developed in 43 patients (45.7%). The median survival after relapse was 6.93 months. Bone marrow was the most frequent site of relapse (21 patients [48.8%]) and conferred a significantly lower 5-year OS of 16.4%. Conclusion Adults with ALL in Mexico had high-risk characteristics and an increased relapse rate; however, the OS after CR was similar to the greatest achieved in developed countries, suggesting that a threshold for curing adult ALL with current therapeutic strategies has been reached.

This paper proposes a reliable fault-tolerant model predictive control applied to drinking water transport networks. After a fault has occurred, the predictive controller should be redesigned to cope with the fault effect. Before starting to apply the fault-tolerant control strategy, it should be evaluated whether the predictive controller will be able to continue operating after the fault appearance. This is done by means of a structural analysis to determine loss of controllability after the fault complemented with feasibility analysis of the optimization problem related to the predictive controller design, so as to consider the fault effect in actuator constraints. Moreover, by evaluating the admissibility of the different actuator-fault configurations, critical actuators regarding fault tolerance can be identified considering structural, feasibility, performance and reliability analyses. On the other hand, the proposed approach allows a degradation analysis of the system to be performed. As a result of these analyses, the predictive controller design can be modified by adapting constraints such that the best achievable performance with some pre-established level of reliability will be achieved. The proposed approach is tested on the Barcelona drinking water transport network., This work has been partially funded by MINECO and FEDER through the Project ECOCIS (Ref. DPI2013-48243-C2-1-R) and Project HARCRICS (Ref. DPI2014-58104-R).

In this paper, three different types of faults (abrupt-additive, gradual-additive and multiplicative) are introduced to two new reconfigurable structures for Fault Tolerant Control (FTC) of a Single Input-Single Output (SISO) non-linear process. The first FTC structure, named MRAC-LPV, is based on an MRAC design using an LPV system, while the second FTC structure is based on an MRAC with a H ∞ Gain Scheduling Controller (MRAC-H ∞ GS-LPV) also designed by using an LPV system. Both MRAC controllers were implemented using the Lyapunov theory methodology because it guarantees the stability of the closed-loop system. The proposed schemes were tested using the nonlinear model of the system. To compare the performance of these schemes, a Coupled-Tank system is used as testbed in which the different types of faults with different magnitudes and different operating points were tested. Results showed that the use of an H ∞ Gain Scheduling Controller in combination with an MRAC improves the FTC performance because the controller was able to deal in an efficient manner with the faults and the changes in the operating points of the nonlinear model of the system.

The effectiveness of reduced-intensity conditioning allogeneic stem cell transplantation (allo- RIC) compared with high-dose chemotherapy followed by autologous stem cell transplantation (auto-SCT) in Hodgkin’s disease (HD) and in non-Hodgkin’s lymphoma (NHL) patients remains poorly defined. The purpose of the study was to demonstrate the usefulness of auto-SCT or allo-SCT, employing a RIC regimen in refractory or relapsed NHL or HD patients. We analyzed the outcome of 71 patients with advanced disease. Twenty-three NHL and 14 HD patients received an allo-RIC using fludarabine, cyclophosphamide, and low-dose busulfan as the conditioning regimen. Sixteen NHL and 18 HD patients received auto-SCT using cyclophosphamide and etoposide as conditioning regimen. All hematopoietic stem cells products were not cryopreserved and the majority of grafts were done on an outpatient basis, including conditioning and post-stem cell infusion care (auto-SCT, 62% and allo-RIC procedure, 91%). The median OS was 45.5 months for the allo-RIC recipients and 53.3 months for auto-SCT recipients. Acute/chronic GVHD incidence in NHL and HL groups was 38%/31% and 14%/7%, respectively. We found no significant difference in overall survival between allo-RIC group and auto-SCT group for NHL patients (P = 0.43) but better OS was observed for auto-SCT group than for allo-SCT group in HL patients (P < 0.001). The relapse rate was higher in autografted patients, both in NHL and HD. Both auto-SCT and allo-RIC appear to be valid treatments for poor-risk patients with relapsed or refractory lymphoma who could not otherwise be cured with conventional salvage regimens.

A new fault detection and diagnosis approach to deal with noisy measurements and correlated variables is presented. Using Auto-Associative Neural Networks ( AANN ) the correlation of the variables is learned from normal operating conditions data. Then, residuals can be computed with this AANN model. By comparing residuals against normal operating conditions thresholds, faults can be detected (and sometimes diagnosed) using a Non-Linear Principal Component Analysis. For noisy variables were previous procedure fails, a second sequential step based on several Adaptive Neuro-Fuzzy Inference Systems ( ANFIS ) is needed. The performance of the approach was validated with a vehicle model. Early results are promising.

In this paper, an original model-based scheme for leak location using pressure sensors in water distribution networks is introduced. The proposed approach is based on a new representation called the Leak Signature Space (LSS) that associates a specific signature to each leak location being minimally affected by leak magnitude. The LSS considers a linear model approximation of the relation between pressure residuals and leaks that is projected onto a selected hyperplane. This new approach allows to infer the location of a given leak by comparing the position of its signature with other leak signatures. Moreover, two ways of improving the method's robustness are proposed. First, by associating a domain of influence to each signature and second, through a time horizon analysis. The efficiency of the method is highlighted by means of a real network using several scenarios involving different number of sensors and considering the presence of noise in the measurements.

Remission induction regimens for acute lymphoblastic leukemia (ALL) in adults induce complete remission (CR) in 60-90% and cure in 20-40%. A cohort study of newly diagnosed patients with ALL treated with mitoxantrone versus doxorubicin was conducted from 2005 to 2013. The primary endpoint was the proportion of CR. Eighty-five patients were included. Fifty-three received induction with doxorubicin and 32 with mitoxantrone. Median follow-up in the cohort was 40.2 months (range 2-95). Twenty-nine patients (90.6%) achieved CR in the mitoxantrone arm compared with 37 (69.8%) in the doxorubicin group (p = 0.032). There was no difference in death or relapse rate (p = 0.095 and 0.075), hematological recovery (p = 0.654), incidence of adverse events (p = 0.6), in-hospital days during induction (p = 0.456) or overall survival (p = 0.105). Induction toxicities were comparable. Mitoxantrone can be safely and effectively used as a frontline anthracycline in adults newly diagnosed with ALL.