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Chimeric antigen receptor T-cell (CAR-T) therapy targeting CD19 has significantly improved outcomes in the treatment of refractory or relapsed (R/R) B-cell non-Hodgkin lymphoma (NHL). Several risk factors including CAR-T cell-related toxicities and their treatments often lead to infectious complications (ICs); however, the pattern and timeline is not well established. We evaluated ICs in 48 patients with R/R B-cell NHL following CAR-T cell therapy at our institution. Overall, 15 patients experienced 22 infection events. Eight infections (4 bacterial, 3 viral and 1 fungal) occurred within the first 30 days and 14 infections (7 bacterial, 6 viral, 1 fungal) between days 31 to 180 following CAR-T infusion. Most infections were mild-to-moderate and fifteen infections involved the respiratory tract. Two patients developed mild-to-moderate COVID-19 infection and one patient a cytomegalovirus reactivation after CAR-T infusion. Two patients developed IFIs: one case each of fatal disseminated candidiasis and invasive pulmonary aspergillosis at day 16 and 77, respectively. Patients with more than 4 prior antitumor regimens and patient's ≥ 65 years had a higher infection rate. Infections in patients with relapsed/refractory B-cell NHL are common after CAR-T despite the use of infection prophylaxis. Age ≥ 65 years and having > 4 prior antitumor treatments were identified as risk factors for infection. Fungal infections carried significant impact in morbidity and mortality, suggesting a role for increase fungal surveillance and/or anti-mold prophylaxis following high-dose steroids and tocilizumab. Four of ten patients developed an antibody response following two doses of SARS-CoV-2 mRNA vaccine. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the indications and management of grade III-IV postoperative complications in patients requiring vacuum-assisted open abdomen after debulking surgery for ovarian carcinomatosis. Retrospective study of prospectively collected data from patients who underwent a cytoreductive surgery by laparotomy for an epithelial ovarian cancer that required postoperative management of an open abdomen. An abdominal vacuum-assisted wound closure (VAWC) was applied in cases of abdominal compartmental syndrome (ACS) or intra-abdominal hypertension, to prevent ACS. The fascia was closed with a suture or a biologic mesh. The primary aim was to achieve primary fascial closure. Secondary outcomes considered included complications of cytoreductive surgery (CRS) and open abdominal wounds (hernia, fistula). Two percent of patients who underwent CRS required VAWC during the study's patient inclusion period. VAWC indications included: (i) seven cases of gastro-intestinal perforation, (ii) three necrotic enterocolitis, (iii) two intestinal ischemia, (iv) three anastomotic leakages and (v) four intra-abdominal hemorrhages. VAWC was used to treat indications (i) to (iv) (which represented 73.7% of cases), to prevent compartmental syndrome. Primary fascia closure was achieved in 100% of cases, in four cases (21.0%) a biologic mesh was used. Median hospital stay was 65 days (range: 18–153). Four patients died during hospitalization, three of these within 30 days of VAWC completion. VAWC for managing open abdominal wounds is a reliable technique to treat surgical post-CRS complications in advanced ovarian cancer and reduces the early post-operative mortality in cases presenting with severe complications. • Vacuum-assisted open abdomen enables the management of grade III-IV postoperative complications after ovarian cytoreduction. • Vacuum-assisted wound closure was applied in cases of abdominal compartmental syndrome. • Primary fascia closure was achieved in 100% of cases after open abdomen using vacuum-assisted wound closure. [ABSTRACT FROM AUTHOR]

Accessed August 20, 2022 7 COVID-19 Treatment Guidelines Panel: Coronavirus Disease 2019 (COVID-19) Treatment Guidelines. COVID-19 patients with severe hypoxemia leading to acute respiratory distress syndrome (ARDS) requiring invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) experience disproportionately high mortality. * Keywords: acute respiratory distress syndrome; baricitinib; clinical trials; COVID-19; ruxolitinib EN acute respiratory distress syndrome baricitinib clinical trials COVID-19 ruxolitinib 1821 1828 8 11/21/22 20221201 NES 221201 Despite remarkable advances in supportive care, antiviral, and immunomodulatory therapies through rigorous clinical trials ([1]), patients with severe COVID-19 continue facing high burden of complications, including prolonged cognitive and physical sequelae, hospitalization, and risk of death. [Extracted from the article]

Simple Summary: Not all cancer patients receiving immunotherapy by immune checkpoint blockade experience a clinical benefit. Our study was aimed at identifying biomarkers that could guide the selection of immunotherapy-responsive patients. Immunotherapy targets two major populations of lymphocytes: CD8 T cells, which directly kill tumor cells, and CD4 T cells, which provide help to CD8 T cells, the role of which in clinical responsiveness to immunotherapy has been less explored. We identified, in the blood of cancer patients, a population of CD4 T cells expressing inhibitory receptors targeted by immunotherapy. We showed that these cells were activated and proliferating, indicating their potential involvement in ongoing immune responses. Accordingly, we showed that they were specific for tumor antigens. In a prospective cohort, we showed that high proportions of these cells prior to therapy were associated with a response to immunotherapy. Tumor-infiltrating exhausted PD-1hiCD39+ tumor-antigen (Ag)-specific CD4 T cells contribute to the response to immune checkpoint blockade (ICB), but their circulating counterparts, which could represent accessible biomarkers, have not been assessed. Here, we analyzed circulating PD-1+CD39+ CD4 T cells and show that this population was present at higher proportions in cancer patients than in healthy individuals and was enriched in activated HLA-DR+ and ICOS+ and proliferating KI67+ cells, indicative of their involvement in ongoing immune responses. Among memory CD4 T cells, this population contained the lowest proportions of cells producing effector cytokines, suggesting they were exhausted. In patients with HPV-induced malignancies, the PD-1+CD39+ population contained high proportions of HPV Ag-specific T cells. In patients treated by ICB for HPV-induced tumors, the proportion of circulating PD-1+CD39+ CD4 T cells was predictive of the clinical response. Our results identify CD39 expression as a surrogate marker of circulating helper tumor-Ag-specific CD4 T cells. [ABSTRACT FROM AUTHOR]

The use of random MAC addresses is considered as an important tool to improve a user's privacy on a Wi-Fi network. Although this technique was proposed since 2014, its implementation was not effective immediately but had an uneven evolution over the following years. This paper studies the evolution of random MAC addresses based on the analysis of data collected in public Wi-Fi networks located in different areas of Latin American countries from 2016 to 2021. Statistical analysis is performed using the analysis of variance technique (ANOVA) that tests whether there are significant differences in the rate of MAC randomization over different periods of time and thereby identified an uneven evolution of the implementation of MAC address randomization measures in mobile devices with different operating systems, and also the massification of these measures from 2019. The development of the massification of randomized MAC addresses and the impact of the existence of centralized and widely controlled operating systems, such as iOS, is evident. [ABSTRACT FROM AUTHOR]

The term 'out-of-the-box surgery' in gynecologic oncology was recently coined to describe the resection of tumor growing out of the endopelvic cavity. In the specific case of pelvic sidewall involvement, a laterally extended pelvic resection may be required. As previously defined by Höckel, this resection requires the en bloc removal of structures including the pelvic sidewall muscles, bones, nerves, and/or major vessels. This complex radical procedure leads to tumor-free margins in more than 75% of the patients, with reliable functional results. The rate of recurrence and overall survival are directly correlated with clear resection margins. Progress in imaging, surgical techniques, and perioperative care currently offer the opportunity to attempt surgical curative resection in selected patients for whom palliative therapy was the only alternative. However, the procedure is associated with a high rate of major postoperative complications affecting up to 60% of patients. Multidisciplinary expert centers are the most likely to achieve this complex surgery with favorable oncological outcomes. The aim of this review is to summarize the key issues of out-of-the-box surgery in gynecologic cancer. • The term 'out-of-the-box surgery' is employed for the resection of tumor growing out of the endopelvic cavity. • The rate of recurrence and overall survival are directly correlated with clear resection margin status. • In selected patients, tumor-free margins may be obtained in more than 75% of the cases. • This ultraradical surgery is associated with major postoperative complications affecting up to 60% of patients. • Multidisciplinary expert centers are the most likely to achieve optimal oncological outcomes. [ABSTRACT FROM AUTHOR]

In engineering education, traditional teaching practices continue to be replaced by inquiry-based learning methods such as problem-based learning, which is now a ubiquitous practice in engineering schools. However, adopting it as the sole learning method curtails the richness of the pedagogical practice. This research proposes a pedagogical innovation by using a joint learning method, example-based learning (EBL) and problem-based learning (PBL), to improve learning outcomes. Using a posttest-only quasi-experimental design, machining laboratory practices in mechanical engineering were designed to use EBL only (control group) in one academic semester and both PBL and EBL (quasi-experimental group) the next academic semester. To account for the difference in cohorts, the difference-in-differences method was used to determine the impact of the addition of PBL. Students provided qualitative data to ascertain their perceptions using the joint method. The addition of the PBL method to the EBL method has a positive but statistically insignificant impact on posttest scores. PBL fosters the acquisition of non-technical skills such as communication, coordination, and teamwork, even when such skills are not taught. The combination of PBL and EBL works in synergy and fosters the development of technical and non-technical skills in engineering educational practice. [ABSTRACT FROM AUTHOR]

Objective: Autosomal recessive human thymidine kinase 2 (TK2) mutations cause TK2 deficiency, which typically manifests as a progressive and fatal mitochondrial myopathy in infants and children. Treatment with pyrimidine deoxynucleosides deoxycytidine and thymidine ameliorates mitochondrial defects and extends the lifespan of Tk2 knock‐in mouse (Tk2KI) and compassionate use deoxynucleoside therapy in TK2 deficient patients have shown promising indications of efficacy. To augment therapy for Tk2 deficiency, we assessed gene therapy alone and in combination with deoxynucleoside therapy in Tk2KI mice. Methods: We generated pAAVsc CB6 PI vectors containing human TK2 cDNA (TK2). Adeno‐associated virus (AAV)‐TK2 was administered to Tk2KI, which were serially assessed for weight, motor functions, and survival as well as biochemical functions in tissues. AAV‐TK2 treated mice were further treated with deoxynucleosides. Results: AAV9 delivery of human TK2 cDNA to Tk2KI mice efficiently rescued Tk2 activity in all the tissues tested except the kidneys, delayed disease onset, and increased lifespan. Sequential treatment of Tk2KI mice with AAV9 first followed by AAV2 at different ages allowed us to reduce the viral dose while further prolonging the lifespan. Furthermore, addition of deoxycytidine and deoxythymidine supplementation to AAV9 + AAV2 treated Tk2KI mice dramatically improved mtDNA copy numbers in the liver and kidneys, animal growth, and lifespan. Interpretation: Our data indicate that AAV‐TK2 gene therapy as well as combination deoxynucleoside and gene therapies is more effective in Tk2KI mice than pharmacological alone. Thus, combination of gene therapy with substrate enhancement is a promising therapeutic approach for TK2 deficiency and potentially other metabolic disorders. ANN NEUROL 2021;90:640–652 [ABSTRACT FROM AUTHOR]

Early-life inflammatory stress increases seizure susceptibility later in life. However, possible sex- and age-specific differences and the associated mechanisms are largely unknown. C57BL/6 mice were bred in house, and female and male pups were injected with lipopolysaccharide (LPS; 100 lg/kg, i.p.) or vehicle control (saline solution) at postnatal day 14 (P14). Seizure threshold was assessed in response to pentylenetetrazol (1% solution, i.v.) in adolescence (;P40) and adulthood (;P60). We found that adult, but not adolescent, mice treated with LPS displayed; 34% lower seizure threshold compared with controls. Females and males showed similar increased seizure susceptibility, suggesting that altered brain excitability was age dependent, but not sex dependent. Whole-cell recordings revealed no differences in excitatory synaptic activity onto CA1 pyramidal neurons from control or neonatally inflamed adolescent mice of either sex. However, adult mice of both sexes previously exposed to LPS displayed spontaneous EPSC frequency approximately twice that of controls, but amplitude was unchanged. Although these changes were not associated with alterations in dendritic spines or in the NMDA/AMPA receptor ratio, they were linked to an increased glutamate release probability from Schaffer collateral, but not temporoammonic pathway. This glutamate increase was associated with reduced activity of presynaptic GABAB receptors and was independent of the endocannabinoid-mediated suppression of excitation. Our new findings demonstrate that early-life inflammation leads to long-term increased hippocampal excitability in adult female and male mice associated with changes in glutamatergic synaptic transmission. These alterations may contribute to enhanced vulnerability of the brain to subsequent pathologic challenges such as epileptic seizures. [ABSTRACT FROM AUTHOR]

Metaphors have been widely used to investigate the perspectives of teachers and students in mathematics. In this report, an instrument was developed, the metaphor continuums, to provide a space for four prospective teachers to discuss their projective identities as teachers and mathematics teacher. Using an argumentation perspective on identity, the responses to the instrument were investigated to determine a tentative manifestation of the participants' projective identity. The participants' provided some evidence of their projective identities as teacher and mathematics teachers being aligned. One participant did not provide evidence of distinguishing between her identity as a mathematics teacher and a teacher. The vehicles, or subject of the metaphors, given to the participants provided varying ways for them to explore their ideas of teaching and learning mathematics. The metaphor continuums showed potential for mathematics teacher educators to receive initial information to help in determining targeted interventions for their students. [ABSTRACT FROM AUTHOR]

Background: Proximal medial gastrocnemius release (PMGR) is a technique that is performed to relieve tension in the Achilles-calcaneus-plantar system when a biomechanical overload is present1-3. One of the main indications for this technique is recalcitrant plantar fasciitis. This procedure may also be useful in second-rocker metatarsalgia or midportion Achilles tendinitis4. It is considered to be an easy and safe method for achieving good results5-7. Description: PMGR is performed with the patient in the prone position. A thigh tourniquet is not utilized. We prefer to use spinal anesthesia, but local anesthesia could be applied along with sedation. A posteromedial incision is made on or just below the posterior knee crease. The crural fascia is divided, and the proximal insertion of the medial gastrocnemius is identified. Performing the "hook maneuver" with a curved dissector is helpful at this step. Only the white fibers are sectioned in order to allow for a lengthening of the muscular fibers that is completed with forceful ankle dorsiflexion. After proper hemostasis has been achieved, the subcutaneous layer and skin are closed, leaving the fascia open. Alternatives: Nonoperative treatment should be the first option, including analgesics, insoles, heel cups, calf-stretching, injections, and extracorporeal shock wave therapy8. Some authors have also suggested that application of a walking cast for 3 to 6 weeks should be attempted9,10. Once all of these treatment options have failed, operative treatment is appropriate. Historically, open plantar fasciotomy was offered to patients with recalcitrant plantar fasciitis, and this treatment continues to be a surgical option. Other procedure, like the Strayer, Vulpius, or Baumann techniques, involve the calf system and are called "gastrocnemius recession." However, these techniques act in the more distal aspect of the calf system compared with PMGR. Rationale: PMGR offers patients with recalcitrant plantar fasciitis rapid recovery and good results. This procedure obviates the complications associated with plantar fasciotomy, in which the medial aspect of the proximal plantar fascia is divided to relieve the overload. A plantar fasciotomy (either open or endoscopic11) risks lateral column overload12 or a painful flatfoot if >50% of the fascia is divided. A long recovery period following plantar fasciotomy has also been described7. On the other hand, other procedures have been utilized to lengthen the Achilles-calcaneus-plantar system to an even greater extent. Techniques like the Silfverskiöld (i.e., medial and lateral proximal gastrocnemius release) or Strayer (i.e., division of the distal aspect of the gastrocnemius fascia) technique present a higher rate of complications (up to 38%), specifically nerve injuries13,14. We consider these procedures (classified as gastrocnemius recession procedures) more properly indicated for patients with neurological diseases or with an equinus contracture. The medial gastrocnemius is the more powerful of the 2 bellies. Releasing the medial head alone offers a robust decrease in tension and is safer than approaching the lateral head of the gastrocnemius15. At the same time, this technique provides a quick recovery for the patient. PMGR can also help those patients with other clinical signs related to gastrocnemius tightness, such as calf cramps and pain or repeated muscle injuries. Moreover, it can be effective in patients with second-rocker metatarsalgia or midportion Achilles tendinitis1,16. Expected Outcomes: PMGR has a reported rate of satisfaction of >80%. Most patients undergoing this procedure experience substantial pain relief within the first 2 to 3 months6,17. PMGR is an outpatient procedure with a short operative time and a rapid return to recreational and labor activities. The complication rate is low, and the most common complications are calf hematomas and delayed wound healing. The present article demonstrates a reduction in pain and good functional results. An improvement in the perception of health-related quality of life, especially in the physical and pain domains of the Short Form-36 questionnaire, was also observed. Important Tips: The prone position allows for direct access to the proximal medial head of the gastrocnemius. Preferably, perform PMGR without a tourniquet in order to assure proper hemostasis. Keep the ankle joint free at the end of operating table because ankle dorsiflexion is a helpful maneuver at some stages in this procedure. Digital (index finger) dissection should be performed among the medial head of the gastrocnemius, the hamstrings, and the posterior aspect of the proximal tibia. The hook maneuver, performed with use of a blunt dissector, is helpful to identify all of the white fibers. Only white fibers should be divided. The surgeon must also make sure to cut the more anterior part of the aponeurosis that is hidden by red fibers. After cutting the white fibers, forceful ankle dorsiflexion is required to obtain full lengthening of the muscle. Proper hemostasis should be achieved to prevent formation of a calf hematoma. Advise the patient to do calf-stretches as soon as pain permits in order to prevent a contracting muscle scar. Acronyms & Abbreviations: PMGR = proximal medial gastrocnemius release ESWT = extracorporeal shock wave therapy SD = standard deviation [ABSTRACT FROM AUTHOR]

Cooney, Shealy, and Arvold (1998) wrote a widely cited article describing the belief structures of prospective teachers and argued that the structures can aid in describing how beliefs change and the influence of authority on the individual. We investigate the impact of this manuscript on the field. To do this, we conducted a literature review (n = 59) of journal articles and proceedings published since 1998 covering the same population and goals of Cooney, Shealy, and Arvold (changing prospective teachers' beliefs) and then conducted an analysis of 101 journal articles citing Cooney, Shealy, and Arvold (1998) to see why the authors cited the piece. We conclude that the impact of Cooney, Shealy, and Arvold's article differs from that of their results and suggest that belief structures should be more carefully investigated by the field. [ABSTRACT FROM AUTHOR]

The topic of open justice has only been little explored perhaps due to its traditionally having been considered a "closed" field. There is still a need to know what open justice really means, to explore the use of information and technology in enabling open justice, and to understand what openness in the judiciary can do to improve government, society, and democracy. This special issue aims to shed light on the concept of openness in the judiciary by identifying and analyzing initiatives across the world. [ABSTRACT FROM AUTHOR]

Early life, systemic inflammation causes long-lasting changes in behavior. To unmask possible mechanisms associated with this phenomenon, we asked whether the intrinsic membrane properties in hippocampal neurons were altered as a consequence of early life inflammation. C57BL/6 mice were bred in-house and both male and female pups from multiple litters were injected with lipopolysaccharide (LPS; 100 µg/kg, i.p.) or vehicle at postnatal day (P)14, and kept until adolescence (P35-P45) or adulthood (P60-P70), when brain slices were prepared for whole-cell and perforated-patch recordings from CA1 hippocampal pyramidal neurons. In neurons of adult male mice pretreated with LPS, the number of action potentials elicited by depolarizing current pulses was significantly increased compared with control neurons, concomitant with increased input resistance, and a lower action potential threshold. Although these changes were not associated with changes in relevant sodium channel expression or differences in capacitance or dendritic architecture, they were linked to a mechanism involving intracellular chloride overload, revealed through a depolarized GABA reversal potential and increased expression of the chloride transporter, NKCC1. in contrast, no significant changes were observed in neurons of adult female mice pretreated with LPS, nor in adolescent mice of either sex. These data uncover a potential mechanism involving neonatal inflammationinduced plasticity in chloride homeostasis, which may contribute to early life inflammation-induced behavioral alterations. [ABSTRACT FROM AUTHOR]

Multiple sclerosis is an autoimmune demyelinating disorder of the CNS, characterized by inflammatory lesions and an underlying neurodegenerative process, which is more prominent in patients with progressive disease course. It has been proposed that mitochondrial dysfunction underlies neuronal damage, the precise mechanism by which this occurs remains uncertain. To investigate potential mechanisms of neurodegeneration, we conducted a functional screening of mitochondria in neurons exposed to the CSF of multiple sclerosis patients with a relapsing remitting (n = 15) or a progressive (secondary, n = 15 or primary, n = 14) disease course. Live-imaging of CSF-treated neurons, using a fluorescent mitochondrial tracer, identified mitochondrial elongation as a unique effect induced by the CSF from progressive patients. These morphological changes were associated with decreased activity of mitochondrial complexes I, III and IV and correlated with axonal damage. The effect of CSF treatment on the morphology of mitochondria was characterized by phosphorylation of serine 637 on the dynamin-related protein DRP1, a post-translational modification responsible for unopposed mitochondrial fusion in response to low glucose conditions. The effect of neuronal treatment with CSF from progressive patients was heat stable, thereby prompting us to conduct an unbiased exploratory lipidomic study that identified specific ceramide species as differentially abundant in the CSF of progressive patients compared to relapsing remitting multiple sclerosis. Treatment of neurons with medium supplemented with ceramides, induced a time-dependent increase of the transcripts levels of specific glucose and lactate transporters, which functionally resulted in progressively increased glucose uptake from the medium. Thus ceramide levels in the CSF of patients with progressive multiple sclerosis not only impaired mitochondrial respiration but also decreased the bioavailability of glucose by increasing its uptake. Importantly the neurotoxic effect of CSF treatment could be rescued by exogenous supplementation with glucose or lactate, presumably to compensate the inefficient fuel utilization. Together these data suggest a condition of 'virtual hypoglycosis' induced by the CSF of progressive patients in cultured neurons and suggest a critical temporal window of intervention for the rescue of the metabolic impairment of neuronal bioenergetics underlying neurodegeneration in multiple sclerosis patients. [ABSTRACT FROM AUTHOR]

Objective: To define the relationship between chronic chikungunya post-viral arthritis disease severity, cytokine response and T cell subsets in order to identify potential targets for therapy. Methods: Participants with chikungunya arthritis were recruited from Colombia from 2019–2021. Arthritis disease severity was quantified using the Disease Activity Score-28 and an Arthritis-Flare Questionnaire adapted for chikungunya arthritis. Plasma cytokine concentrations (interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, interferon-γ and tumor necrosis factor (TNF)) were measured using a Meso Scale Diagnostics assay. Peripheral blood T cell subsets were measured using flow cytometry. Results: Among participants with chikungunya arthritis (N = 158), IL-2 levels and frequency of regulatory T cells (Tregs) were low. Increased arthritis disease activity was associated with higher levels of inflammatory cytokines (IL-6, TNF and CRP) and immunoregulatory cytokine IL-10 (p<0.05). Increased arthritis flare activity was associated with higher Treg frequencies (p<0.05) without affecting T effector (Teff) frequencies, Treg/Teff ratios and Treg subsets. Finally, elevated levels of IL-2 were correlated with increased Treg frequency, percent Tregs out of CD4+ T cells, and Treg subsets expressing immunosuppressive markers, while also correlating with an increased percent Teff out of live lymphocytes (p<0.05). Conclusion: Chikungunya arthritis is characterized by increased inflammatory cytokines and deficient IL-2 and Treg responses. Greater levels of IL-2 were associated with improved Treg numbers and immunosuppressive markers. Future research may consider targeting these pathways for therapy. [ABSTRACT FROM AUTHOR]

Indeed, among ITRs with CDI during indexed admission, CDI was the leading cause of 30-day readmission but overall, the 30-day readmission rate was comparable between CDI and non-CDI ITRs (36.7% vs. 38%, I p i = .95). Compared with the general population, solid-organ transplant (SOT) recipients experience a greater incidence and severity of I Clostridioides difficile i infection (CDI), often leading to significant morbidity and mortality.[1] Risk factors for recurrent CDI such as advanced age, immunocompromised state, and severe infection at initial presentation are well described in SOT recipients. [Extracted from the article]

The risk of infection after heart transplantation is highest within the first year and represents the leading cause of early mortality. In this cohort of patients enrolled in the Outcomes AlloMap Registry (OAR), we sought to describe infection episodes (IEp) resulting in hospitalization, in the early (<1 year) and late (≥1 year) post-transplant period and determine the impact of immunosuppression on incidence of infection. The primary aim was to assess the incidence and nature of IEp. The secondary aim was to evaluate the effect of potential risk factors, such as recipient age; sex; body mass index; panel-reactive antibodies; cytomegalovirus (CMV) primary mismatch; prednisone, tacrolimus, and sirolimus levels; and gene expression profile (GEP) score, in the development of IEp. The OAR comprises 1,504 patients, of whom 220 patients (14.6%) had an IEp during a median follow-up period of 382 days (interquartile range [IQR] 230 to 579 days). The cause-specific 5-year hazard ratio for any infection was 2.029 (p = 0.12). The pattern of early infection was consistent with nosocomial and opportunistic causes, whereas later infection was consistent with late-onset opportunistic and community-acquired etiologies. Sixty-two percent of the infections occurred early. In the time-dependent analysis, higher prednisone dose (log prednisone, hazard ratio [HR] 1.30, p = 0.022) was the most significant risk factor for all IEp. In the OAR cohort, the majority of infections occurred within 1 year after transplantation. Clinicians may consider more aggressive prednisone withdrawal in low-risk patients to reduce IEp. [ABSTRACT FROM AUTHOR]

• Belief structures provide more information than belief content for changing beliefs. • A new belief structure, adaptive idealist, is introduced. • An adaptive idealist interprets experiences and vocabulary to justify beliefs. One goal of teacher mathematics education is to transform teachers' beliefs to more closely align with beliefs that promote desired teaching practices. However, beliefs are difficult to change. A construct that helps to explain how and why mathematics teachers' beliefs change is that of belief structures (Cooney et al., 1998). We expand upon belief structures to add a new construct: adaptive idealist. In this case study, we used information gleaned from interviews and reflective papers to introduce a prospective secondary mathematics teacher, describe her beliefs and shifts in beliefs, identify a resistance to change that resonated with our other experiences, and conclude that this new belief structure allows us to explain her reactions and interpretations within our secondary mathematics education program. [ABSTRACT FROM AUTHOR]

Diarrhea in hematopoietic stem‐cell transplantation (HSCT) remains a multifactorial challenge that demands a nuanced diagnostic approach. The causes of infectious diarrhea in HSCT recipients are diverse and influenced by patient‐specific risk factors, the post‐transplant timeline, and local epidemiology. During the past decade, our understanding of diarrhea in HSCT has witnessed a transformative shift through the incorporation of gastrointestinal (GI) multiplex polymerase chain reaction (PCR) panels. However, the judicious application of these panels is imperative to avoid overtesting and prevent adverse outcomes. The challenge lies in distinguishing between the diverse causes of diarrhea, ascertaining the clinical significance of detected pathogens, and navigating the diagnostic uncertainty presented by several non‐infectious conditions such as mucositis, intestinal dysbiosis, and acute graft‐versus‐host disease (aGvHD), all of which mimic infection. This review examines the landscape of infectious diarrhea in the HSCT population, encompassing both established (e.g., Cytomegalovirus, Clostridioides difficile, and norovirus) and emerging pathogens (e.g., sapoviruses, astroviruses). We propose a multifaceted diagnostic algorithm that combines clinical assessment, risk stratification, and tailored utilization of molecular platforms. While multiplex GI panels present invaluable opportunities for rapid and comprehensive pathogen detection, their judicious use is pivotal in preserving diagnostic stewardship. Customization of diagnostic algorithms tailored to local epidemiology ensures optimal patient care and resource utilization. [ABSTRACT FROM AUTHOR]

In analyzing the actions undertaken by victimized women forced disappearance in Granada, (Antioquia) and the incidents that these actions have on their senses of life, it is necessary to investigate the ways that victimized women have given a new meaning to the fact related to disappearance, due to the lack of significance between the state and the citizenry. In this sense, the research project becomes relevant in the phenomenological study as a way of analyzing each one of the phenomena represented in the forced disappearance, which allows to narrate and to describe each one of the affections, actions and incidents of each of the victimized women of the Association of Victims of Granada (Asovida). For this reason, the logotherapeutic approach is necessary as a methodological proposal for the resignification of the senses of life in order to channel each of the experiences as a guideline for the restoration of each one of their rights, in the construction of peace. [ABSTRACT FROM AUTHOR]

The shaping of individual cells requires a tight coordination of cell mechanics and growth. However, it is unclear how information about the mechanical state of the wall is relayed to the molecular processes building it, thereby enabling the coordination of cell wall expansion and assembly during morphogenesis. Combining theoretical and experimental approaches, we show that a mechanical feedback coordinating cell wall assembly and expansion is essential to sustain mating projection growth in budding yeast (Saccharomyces cerevisiae). Our theoretical results indicate that the mechanical feedback provided by the Cell Wall Integrity pathway, with cell wall stress sensors Wsc1 and Mid2 increasingly activating membrane-localized cell wall synthases Fks1/2 upon faster cell wall expansion, stabilizes mating projection growth without affecting cell shape. Experimental perturbation of the osmotic pressure and cell wall mechanics, as well as compromising the mechanical feedback through genetic deletion of the stress sensors, leads to cellular phenotypes that support the theoretical predictions. Our results indicate that while the existence of mechanical feedback is essential to stabilize mating projection growth, the shape and size of the cell are insensitive to the feedback. [ABSTRACT FROM AUTHOR]

Background. Identification of fungi causing invasive fungal disease (IFD) is critical for guiding antifungal therapy. We describe the performance and clinical impact of a targeted panfungal polymerase chain reaction (PCR) amplicon sequencing assay for culture-independent diagnosis of IFD. Methods. Between January 2009 and September 2016, 233 specimens, consisting of fresh and formalin-fixed, paraffin-embedded (FFPE) tissues and sterile body fluids with known diagnosis of IFD based on reference method results (n = 117), and specimens with negative fungal culture, but with microscopic and ancillary findings indicative of IFD (n = 116), were included. PCR amplicons from the internal transcribed spacer 2 and the D2 region of 28S ribosomal RNA gene were sequenced and fungi identified. Results. Sensitivity and specificity of fungal sequencing in specimens with known diagnosis were 96.6% (95% confidence interval [CI], 87.4%-99.4%; 58/60) and 98.2% (95% CI, 89.4%-99.9%; 56/57). In patients with suspected IFD, the diagnostic yield of fungal sequencing was 62.9% (73/116) overall and 71.3% (57/80) in patients classified with proven IFD based on the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and Mycoses Study Group (EORTC/MSG) criteria. Samples obtained by open biopsy had a significantly higher diagnostic yield (71.5% [40/56]) compared with core-needle biopsy (50% [17/34] P = .04) and fine needle aspiration (0% [0/2]; P = .009). Additionally, D2 sequencing diagnosed 5 cases of invasive protozoal infections due to Toxoplasma gondii (n = 3), Trypanosoma cruzi, and Leishmania species. Sequencing results altered patient management in the majority of suspected cases. Conclusions. The targeted fungal sequencing assay allowed accurate identification of fungi causing IFD and additionally provided partial-protozoal coverage. The diagnostic yield was dependent on the amount of tissue available for testing. [ABSTRACT FROM AUTHOR]

Surface topography measurement for metal additive manufacturing (AM) is a challenging task for contact and noncontact methods. We present an experimental investigation of the use of coherence scanning interferometry (CSI) for measuring AM surfaces. Our approach takes advantage of recent technical enhancements in CSI, including high dynamic range for light level and adjustable data acquisition rates for noise reduction. The investigation covers several typical metal AM surfaces made from different materials and AM processes. Recommendations for measurement optimization balance three aspects: data coverage, measurement area, and measurement time. This study also presents insight into areas of interest for future rigorous examination, such as measuring noise and further development of guidelines for measuring metal AM surfaces. [ABSTRACT FROM AUTHOR]

Objective: Thymidine kinase 2 (TK2), a critical enzyme in the mitochondrial pyrimidine salvage pathway, is essential for mitochondrial DNA (mtDNA) maintenance. Mutations in the nuclear gene, TK2, cause TK2 deficiency, which manifests predominantly in children as myopathy with mtDNA depletion. Molecular bypass therapy with the TK2 products, deoxycytidine monophosphate (dCMP) and deoxythymidine monophosphate (dTMP), prolongs the life span of Tk2-deficient (Tk2-/- ) mice by 2- to 3-fold. Because we observed rapid catabolism of the deoxynucleoside monophosphates to deoxythymidine (dT) and deoxycytidine (dC), we hypothesized that: (1) deoxynucleosides might be the major active agents and (2) inhibition of deoxycytidine deamination might enhance dTMP+dCMP therapy.Methods: To test these hypotheses, we assessed two therapies in Tk2-/- mice: (1) dT+dC and (2) coadministration of the deaminase inhibitor, tetrahydrouridine (THU), with dTMP+dCMP.Results: We observed that dC+dT delayed disease onset, prolonged life span of Tk2-deficient mice and restored mtDNA copy number as well as respiratory chain enzyme activities and levels. In contrast, dCMP+dTMP+THU therapy decreased life span of Tk2-/- animals compared to dCMP+dTMP.Interpretation: Our studies demonstrate that deoxynucleoside substrate enhancement is a novel therapy, which may ameliorate TK2 deficiency in patients. Ann Neurol 2017;81:641-652. [ABSTRACT FROM AUTHOR]

During the last decades natural polymers have become more and more frequent to replace traditional inorganic stabilizers in building materials. The purpose of this research is to establish a comparison between the most conventional building material solutions for load-bearing walls and a type of biomaterial. This comparison will focus on load-bearing walls as used in a widespread type of twentieth century dwelling construction in Europe and still used in developing countries nowadays. To carry out this analysis, the structural and thermal insulation characteristics of different construction solutions are balanced. The tool used for this evaluation is the life cycle assessment throughout the whole lifespan of these buildings. This research aims to examine the environmental performance of each material assessed: fired clay brick masonry walls (BW), concrete block masonry walls (CW), and stabilized soil block masonry walls (SW) stabilized with natural fibers and alginates. These conventional and new materials are evaluated from the point of view of both operational and embodied energy. [ABSTRACT FROM AUTHOR]

Fungal mesh infections are a rare complication of hernia repairs with mesh. The first case of Coccidioides spp. mesh infection is described, and a systematic literature review of all known fungal mesh infections was performed. Nine cases of fungal mesh infection are reviewed. Female and male patients are equally represented, median age is 49.5 years, and critical illness and preinfection antibiotic use were common. Fungal mesh infections are rare, but potentially fatal, complications of hernias repaired with mesh. [ABSTRACT FROM AUTHOR]

This paper is concerned with a scalar nonlinear convolution equation, which appears naturally in the theory of traveling waves for monostable evolution models. First, we prove that, at each end of the real line, every bounded positive solution of the convolution equation should either be separated from zero or be exponentially converging to zero. This dichotomy principle is then used to establish a general theorem guaranteeing the uniform persistence and existence of semi-wavefront solutions to the convolution equation. Finally, we apply our theoretical results to several well-studied classes of evolution equations with asymmetric non-local and non-monotone response. We show that, contrary to the symmetric case, these equations can possess simultaneously stationary, expansion and extinction waves. [ABSTRACT FROM AUTHOR]

Abstract: We present a monostable delayed reaction–diffusion equation with the unimodal birth function which admits only non-monotone wavefronts. Moreover, these fronts are either eventually monotone (in particular, such is the minimal wave) or slowly oscillating. Hence, for the Mackey–Glass type diffusive equations, we answer affirmatively the question about the existence of non-monotone non-oscillating wavefronts. As it was recently established by Hasik et al. and Ducrot et al., the same question has a negative answer for the KPP-Fisher equation with a single delay. [Copyright &y& Elsevier]

Simple Summary: Early-stage cervical cancer treatment modalities changed over the decades from open radical hysterectomy to minimally invasive surgery (MIS) and back to laparotomy after the results of a randomized controlled trial that showed a higher risk of disease recurrence in MIS. We aimed to evaluate the overall survival and recurrence-free survival and to assess disease recurrence in early-stage cervical cancer patients treated with minimally invasive surgery over a period of 20 years. Our results show that MIS can still be considered for tumors ≤ 2 cm subject to first conization followed by surgery with the Schautheim procedure and extended pelvic lymphadenectomy. We also found that tumors > 3 cm should preferably be managed with concomitant chemoradiation and brachytherapy. (1) This study aims to evaluate the overall survival (OS) and recurrence-free survivals (RFS) and assess disease recurrence of early-stage cervical cancer (ESCC) patients treated with minimally invasive surgery (MIS). (2) This single-center retrospective analysis was performed between January 1999 and December 2018, including all patients managed with MIS for ESCC. (3) All 239 patients included in the study underwent pelvic lymphadenectomy followed by radical hysterectomy without the use of an intrauterine manipulator. Preoperative brachytherapy was performed in 125 patients with tumors measuring 2 to 4 cm. The 5-year OS and RFS rates were 92% and 86.9%, respectively. Multivariate analysis found two significant factors associated with recurrence: previous conization with HR = 0.21, p = 0.01, and tumor size > 3 cm with HR = 2.26, p = 0.031. Out of the 33 cases of disease recurrence, we witnessed 22 disease-related deaths. Recurrence rates were 7.5%, 12.9%, and 24.1% for tumors measuring ≤ 2 cm, 2 to 3 cm, and > 3 cm, respectively. Tumors ≤ 2 cm were mostly associated with local recurrences. Tumors > 2 cm were frequently associated with common iliac or presacral lymph node recurrences. (4) MIS may still be considered for tumors ≤ 2 cm subject to first conization followed by surgery with the Schautheim procedure and extended pelvic lymphadenectomy. Due to the increased rate of recurrence, a more aggressive approach might be considered for tumors > 3 cm. [ABSTRACT FROM AUTHOR]

We develop an explicit algebraic Reynolds stress model (EARSM) for high-speed compressible shear flows and validate the model with direct numerical simulation (DNS) data of homogeneous shear flow and experimental data of high-speed mixing-layers. Starting from a pressure-strain correlation model that incorporates compressibility effects, the weak-equilibrium assumption is invoked to derive the EARSM closure expression. The resulting closure is fully explicit and physically realizable and is a function of mean flow strain rate, rotation rate, turbulent kinetic energy, dissipation rate, and gradient Mach number. Homogeneous shear flow calculations show that the model captures the asymptotic behavior of DNS quite well. Linear EARSM calculations of a plane supersonic mixing-layer are performed, and comparison with experimental data shows good agreement. Salient results are agreement of streamwise velocity similarity profiles, mixing-layer spreading rates, and capturing the Langley curve trend. [ABSTRACT FROM AUTHOR]

Abstract: The process of designing and calculating railway catenary infrastructure, as the way it is carried out currently, is very complex and time consuming. It is necessary expert knowledge of different fields, like design and structural calculus, technical security, legal normative, topography, etc. This process consists of several stages aimed at choosing a design, checking requirements, and calculating structural feasibility, so the communication among the experts may be quite slow. In order to reduce time and effort invested in this process, we propose a system that allows to automate its stages and tasks. Our system provides a valid solution per structure, that complies with design and structural constraints, and with existing railway regulations. The proposed system has been integrated in a high-productivity software tool, that avoids human mistakes due to hand-calculation, allows users a fast design and calculation, and exploits the ability of current computers to run tasks concurrently so as to speed up the process. The computational performance and complexity of the tool, as well as statistics values, are analysed by designing and calculating up to 2048 heterogeneous support structures. Besides, the tool is evaluated through a study case based on a real railway route, obtaining an overall improvement of 82.33% in time invested over the existing process. [Copyright &y& Elsevier]

Abstract: The design of overhead knuckle junctions in railway electrification is a crucial and complex problem. Non-optimal overhead knuckle junction designs cause limitations in train speed and, most important, malfunctions and breakages. Most railway companies have regulations for the design of overhead knuckle junctions. Those regulations have been defined by the experience, but, as far as we know, there are no computerized software tools to help with the task of designing and testing optimal solutions for overhead knuckle junctions. In this paper we present a simulator that allows to look for optimal configurations of overhead knuckle junctions. The simulator starts from a model based on the description of the problem that includes all the significant elements that may affect the design process, in order to find an optimal solution in terms of reliability and safety. The obtained design will be the more reliable to face failures, such as excessive wire and pantograph wears, wrong geometry configurations of the catenary, or electricity supply notches. The simulator also allows to evaluate current designs, so as to prove their possible flaws. This paper describes the simulation algorithm developed, the input data needed to define the experiments, and the achieved results. As the simulator requires heavy computational resources, high productivity parallel issues have been included in the implementation to exploit current multi-core processors. The validation and performance evaluations were made in the paper through the simulation of overhead knuckle junction designs over real switches. Their analysis will show the feasibility and applicability of our simulator. [Copyright &y& Elsevier]

Modern water policy requires new kinds of economic information in order to improve the ability of stakeholders and water authorities to analyze the whole set of alternatives available, to provide transparency and to assess and adapt water decisions to the emerging water management challenges. Considering this, we present an overview of the main drivers of economic information in the European water policy agenda as defined by the Water Framework Directive. After a brief introduction, the paper explains how basic economic statistics have been used to carry out the economic analysis of water use for the preparation of river basin management plans. We present the strategies used to enhance the usefulness of the economic information already available. The paper ends with a reflection on what parts of the economic information gaps have been satisfactorily dealt with and what the remaining gaps are. [ABSTRACT FROM AUTHOR]

P. micra is an anaerobic Gram-positive cocci, and a known commensal organism of the human oral cavity and gastrointestinal tract. Although it has been classically described in association with endodontic disease and peritonsillar infection, recent reports have highlighted the role of P. micra as the primary pathogen in the setting of invasive infections. In its most recent taxonomic classification, P. micra has never been reported causing infectious endocarditis in humans. Here, we describe a 71 year-old man who developed severe native valve endocarditis complicated by aortic valvular destruction and perivalvular abscess, requiring emergent surgical intervention. Molecular sequencing enabled identification of P. micra . [ABSTRACT FROM AUTHOR]

The article discusses the diet of Eleutherodactylus coqui, a tree frog with a wide distribution throughout the island of Puerto Rico.

OBJECTIVES: Brushing, the standard sampling method at endoscopic retrograde cholangiography (ERC), lacks sensitivity for cancer detection. We assessed a novel sampling method using a grasping basket. METHODS: Fifty-six patients with a suspected malignant biliary stricture were randomized to biliary sampling at ERC using a basket (basket group, N = 30) or a brush (brush group, N = 26), followed by the alternate device. When deemed necessary, strictures were dilated (using 6-mm balloons exclusively). The primary end point was sensitivity for cancer detection at cytopathological examination of the first sample collected in each patient; the cytopathologist was blinded to clinical details and sampling method. All analyses followed an intention-to-treat principle. RESULTS: All 56 patients had successful sampling with both techniques; 50 (89%) had a final diagnosis of malignant stricture. Sensitivity for cancer detection with the first sample collected in each patient was significantly higher in the basket compared to brush group (20/25 [80%] vs 12/25 [48%], respectively, P= 0.018, OR 4.33, 95% CI 1.24–15.21). Seventeen (34%) of the 50 sample pairs collected from malignant cases showed discordant cytopathological results: 15 patients had a positive basket and a negative brush result while two had the inverse association ( P= 0.002, OR 7.5, 95% CI 1.65–47.44). Basketting more frequently yielded positive samples from malignant strictures in case of presampling balloon dilation (27/32 [84%] vs 10/18 [56%], respectively, P= 0.043, OR 4.32, 95% CI 1.14–16.37). Specificity was 100% (both methods). CONCLUSION: Biliary sampling at ERC using a dedicated basket provided a significantly higher sensitivity for cancer detection than brushing; presampling stricture dilation significantly increased sensitivity. [ABSTRACT FROM AUTHOR]

The development of relational databases from which simulation models can access data needed to describe the systems being modeled is fundamental to integrated river basin management, especially in shared, transboundary basins. Creating a geographically referenced database, a geodatabase, for the Rio Grande/Rio Bravo Basin represents the first major attempt to establish a more complete understanding of the basin as a whole, using both Mexican and United States geospatial and temporal water resources data. From the geodatabase, it is possible to obtain information about climatology, water availability, water uses, hydraulic infrastructure, and watershed properties in the basin. These data can be used in simulation models to calculate the state of basin water availability under different climatic and development scenarios and management plans in the future. This geodatabase is intended to be a tool to assist in sharing data to enhance binational cooperation between Mexico and the United States concerning water in this basin, providing accurate and reliable data necessary for analysis and resolution of water resources issues. [ABSTRACT FROM AUTHOR]

Introduction. Anaerobic bacteria are important etiological agents of infections linked to human morbidity and mortality. Nevertheless, the limited development of most Costa Rican health care facilities with respect to the isolation and manipulation of anaerobic bacteria prevents the compilation of precise data on the prevalence of this sort of bacteria in the country. Objective. To assess the occurrence of anaerobic bacteria in clinical samples collected in a regional hospital in Costa Rica. Material and Methods. During 18 months, anaerobic bacteria were cultivated from diverse aspirates following a standardized protocol for sample collection and isolation developed for this study. Results. Forty seven anaerobic bacteria were isolated from 22 of 46 samples analyzed (48% of prevalence). While 25 of these organisms exhibited Gram-negative staining (53%), 22 isolates were characterized as Gram-positive (47%). Mostbacteria were allocated to the genus Bactero ides (42%), followed by Eggerthella (13%) and Propionibacterium (11%). A limited number of isolates was identified as Prevotella sp., Bifidobacterium sp., Porphyromonas sp., or Fusobacterium sp. Discussion. Although traditional procedures for sample collection and isolation of anaerobic bacteria are painstaking, a diversity of anaerobic species, including very strict and fastidious species, was isolated with the practical method applied in the current investigation. On account of this remark, we urge others to implement our protocol in their health care facilities, as this would likely help to define more precisely the role that anaerobic bacteria play in clinical infections. [ABSTRACT FROM AUTHOR]

The tubby mouse, which shows late-onset obesity and neurosensory deficits, arises from a mutation in the Tub gene. Tub shares homology with the genes for tubby-like proteins Tulp1, Tulp2 and Tulp3. Ablation of Tub, Tulp1 or Tulp3 causes disease phenotypes that are indicative of their importance in nervous-system function and development. Despite this importance, the biochemical functions of tubby-like proteins are only now beginning to be understood. At present, data indicate that tubby-like proteins might function as heterotrimeric-G-protein-responsive intracellular signalling factors, although an array of data also implicates them in other processes. [ABSTRACT FROM AUTHOR]

Reveals the discovery of frameshift mutations within the 5' coding region of recombination activating gene 1 in Omenn's syndrome . Nucleotide mutations and corresponding alterations in the protein sequence of the patients; Proposed mechanism for the development of immunodeficiency in a subset of Ommen's syndrome patients.

• Vaginal brachytherapy remains the main treatment for intermediate operated endometrial cancer, with very low rates of local relapse and an acceptable toxicity profile. Brachytherapy of the vaginal dome is the recommended adjuvant treatment for intermediate-risk endometrial cancer. This study assessed the results of dosimetric planning of high-dose-rate brachytherapy exclusively in the first treatment session. Study design: This retrospective study included all patients who underwent hysterectomy for endometrial cancer followed by adjuvant brachytherapy of the vaginal dome between 2012 and 2015. Local recurrence rates, overall survival (OS) rates, recurrence-free survival (RFS) rates, and related acute and late toxicity rates were evaluated. This analysis included 250 patients, of whom 208 were considered to be at high–intermediate risk of disease recurrence. After a median follow-up of 56 months, the cumulative incidence of local recurrence was 4.8% at 3 years [95% confidence interval (CI) 2.8–8.3] and 7.8% at 5 years (95% CI 4.8–12.6). The 5-year OS rate was 86.2% (95% CI 80.6–90.3), and the 5-year RFS rate was 77.5% (95% CI 71.1–82.7). Acute toxicity occurred in 20 (8%) patients, of which two patients had grade ≥3 toxicity. Only one patient (0.4%) presented with late grade ≥3 toxicity. These findings confirm the tolerability of this brachytherapy approach, indicating minimal cases of late grade ≥3 toxicity, associated with a good 5-year OS rate. With the advent of molecular prognostic factors, the current focus revolves around discerning those individuals who gain the greatest benefit from adjuvant therapy, and tailoring treatment more effectively. [ABSTRACT FROM AUTHOR]

Background: Clinical prevention is a critical component of primary care residency training. How well residents do preventive services is one measure of the adequacy of their training.Methods: To assess the level of preventive health care in a university internal medicine residency clinic, we conducted a randomized retrospective review of 225 patient records.Results: We documented preventive services in only 39% of potentially appropriate instances. Cholesterol screening occurred in 53% of eligible cases, breast examination in 41%, mammogram in 69%, Papanicolaou's smear in 53%, estrogen replacement therapy (ERT) in 41%, fecal occult blood testing in 30%, flexible sigmoidoscopy in 18%, influenza vaccination in 65%, pneumococcal vaccination in 44%, and tetanus immunization in only 9%. Male residents were significantly less likely than females to order mammograms or offer ERT.Conclusions: Compared to earlier studies of similar design, we found that the level of preventive health care has improved during residency training, but remains unacceptably low. [ABSTRACT FROM AUTHOR]

Proposes a mathematical model based on the competition between neural networks. Competition between the neural network controlling lever-pressing response during variable-interval schedules of reinforcement with other behavior-controlling networks; Expression of the behavior by a winner-take-all mechanism.