Heat bounds and the blowtorch theorem

We study driven systems with possible population inversion and we give optimal bounds on the relative occupations in terms of released heat. A precise meaning to Landauer's blowtorch theorem (1975) is obtained stating that nonequilibrium occupations are essentially modified by kinetic effects. Towards very low temperatures we apply a Freidlin-Wentzel type analysis for continuous time Markov jump processes. It leads to a definition of dominant states in terms of both heat and escape rates.Comment: 11 pages; v2: minor changes, 1 reference adde

The utility of chest ultrasound-guided fine-needle biopsy in the diagnosis of plasmacytoma

Background. Plasmacytoma is a plasma cell dyscrasia originating from a single clone of plasma cells of B-lymphocyte lineage and produces a monoclonal immunoglobulin. Transthoracic fine-needle aspiration (TTNA) under ultrasound (US) guidance is a well-validated technique for the diagnosis of many neoplasms and has been shown to be safe and cost effective, with diagnostic yields comparable to more invasive techniques. However, the role of TTNA in the diagnosis of thoracic plasmacytoma is not well established. Objective. The aim of this study was to assess the utility of TTNA and cytology in confirming a diagnosis of plasmacytoma. Methods. All cases of plasmacytoma diagnosed from January 2006 to December 2017 by the Division of Pulmonology, Tygerberg Hospital, were retrospectively identified. All patients who underwent an US-guided TTNA and of whose clinical records could be retrieved were included in this cohort. The International Myeloma Working Group’s definition of a plasmacytoma was used as the gold standard. Results. A total of 12 cases of plasmacytoma were identified and 11 patients included (one patient was excluded owing to missing medical records). Six of the 11 patients (mean age 59.5 ± 8.5 years) were male. Radiologically, most had multiple lesions (n=7), most commonly bony (n=6) with vertebral body involvement (n=5) and pleural-based lesions (n=2). Rapid onsite evaluation (ROSE) was performed and documented in 6 of the 11 cases, and a provisional diagnosis of plasmacytoma was suggested in 5 of the 6 patients (83.3%). The final laboratory cytological diagnoses of all 11 cases were compatible with plasmacytoma which was further confirmed via a bone marrow biopsy (n=4) and by serum electrophoresis (n=7). Conclusion. US-guided fine-needle aspiration is feasible and is useful to confirm a diagnosis of plasmacytoma. Its minimally invasive nature may be the ideal investigation of choice in suspected cases

Perception versus reality: A National Cohort Analysis of the surgery-first approach for resectable pancreatic cancer

INTRODUCTION: Although surgical resection is necessary, it is not sufficient for long-term survival in pancreatic ductal adenocarcinoma (PDAC). We sought to evaluate survival after up-front surgery (UFS) in anatomically resectable PDAC in the context of three critical factors: (A) margin status; (B) CA19-9; and (C) receipt of adjuvant chemotherapy. METHODS: The National Cancer Data Base (2010-2015) was reviewed for clinically resectable (stage 0/I/II) PDAC patients. Surgical margins, pre-operative CA19-9, and receipt of adjuvant chemotherapy were evaluated. Patient overall survival was stratified based on these factors and their respective combinations. Outcomes after UFS were compared to equivalently staged patients after neoadjuvant chemotherapy on an intention-to-treat (ITT) basis. RESULTS: Twelve thousand and eighty-nine patients were included (n = 9197 UFS, n = 2892 ITT neoadjuvant). In the UFS cohort, only 20.4% had all three factors (median OS = 31.2 months). Nearly 1/3rd (32.7%) of UFS patients had none or only one factor with concomitant worst survival (median OS = 14.7 months). Survival after UFS decreased with each failing factor (two factors: 23 months, one factor: 15.5 months, no factors: 7.9 months) and this persisted after adjustment. Overall survival was superior in the ITT-neoadjuvant cohort (27.9 vs. 22 months) to UFS. CONCLUSION: Despite the perceived benefit of UFS, only 1-in-5 UFS patients actually realize maximal survival when known factors highly associated with outcomes are assessed. Patients are proportionally more likely to do worst, rather than best after UFS treatment. Similarly staged patients undergoing ITT-neoadjuvant therapy achieve survival superior to the majority of UFS patients. Patients and providers should be aware of the false perception of \u27optimal\u27 survival benefit with UFS in anatomically resectable PDAC

Basic Subsistence Needs and Overall Health Among Human Immunodeficiency Virus-infected Homeless and Unstably Housed Women

Some gender differences in the progression of human immunodeficiency virus (HIV) infection have been attributed to delayed treatment among women and the social context of poverty. Recent economic difficulties have led to multiple service cuts, highlighting the need to identify factors with the most influence on health in order to prioritize scarce resources. The aim of this study was to empirically rank factors that longitudinally impact the health status of HIV-infected homeless and unstably housed women. Study participants were recruited between 2002 and 2008 from community-based venues in San Francisco, California, and followed over time; marginal structural models and targeted variable importance were used to rank factors by their influence. In adjusted analysis, the factor with the strongest effect on overall mental health was unmet subsistence needs (i.e., food, hygiene, and shelter needs), followed by poor adherence to antiretroviral therapy, not having a close friend, and the use of crack cocaine. Factors with the strongest effects on physical health and gynecologic symptoms followed similar patterns. Within this population, an inability to meet basic subsistence needs has at least as much of an effect on overall health as adherence to antiretroviral therapy, suggesting that advances in HIV medicine will not fully benefit indigent women until their subsistence needs are met

Global report on preterm birth and stillbirth (2 of 7): discovery science

<p>Abstract</p> <p>Background</p> <p>Normal and abnormal processes of pregnancy and childbirth are poorly understood. This second article in a global report explains what is known about the etiologies of preterm births and stillbirths and identifies critical gaps in knowledge. Two important concepts emerge: the continuum of pregnancy, beginning at implantation and ending with uterine involution following birth; and the multifactorial etiologies of preterm birth and stillbirth. Improved tools and data will enable discovery scientists to identify causal pathways and cost-effective interventions.</p> <p>Pregnancy and parturition continuum</p> <p>The biological process of pregnancy and childbirth begins with implantation and, after birth, ends with the return of the uterus to its previous state. The majority of pregnancy is characterized by rapid uterine and fetal growth without contractions. Yet most research has addressed only uterine stimulation (labor) that accounts for <0.5% of pregnancy.</p> <p>Etiologies</p> <p>The etiologies of preterm birth and stillbirth differ by gestational age, genetics, and environmental factors. Approximately 30% of all preterm births are indicated for either maternal or fetal complications, such as maternal illness or fetal growth restriction. Commonly recognized pathways leading to preterm birth occur most often during the gestational ages indicated: (1) inflammation caused by infection (22-32 weeks); (2) decidual hemorrhage caused by uteroplacental thrombosis (early or late preterm birth); (3) stress (32-36 weeks); and (4) uterine overdistention, often caused by multiple fetuses (32-36 weeks). Other contributors include cervical insufficiency, smoking, and systemic infections. Many stillbirths have similar causes and mechanisms. About two-thirds of late fetal deaths occur during the antepartum period; the other third occur during childbirth. Intrapartum asphyxia is a leading cause of stillbirths in low- and middle-income countries.</p> <p>Recommendations</p> <p>Utilizing new systems biology tools, opportunities now exist for researchers to investigate various pathways important to normal and abnormal pregnancies. Improved access to quality data and biological specimens are critical to advancing discovery science. Phenotypes, standardized definitions, and uniform criteria for assessing preterm birth and stillbirth outcomes are other immediate research needs.</p> <p>Conclusion</p> <p>Preterm birth and stillbirth have multifactorial etiologies. More resources must be directed toward accelerating our understanding of these complex processes, and identifying upstream and cost-effective solutions that will improve these pregnancy outcomes.</p

Oral abstracts of the 21st International AIDS Conference 18-22 July 2016, Durban, South Africa

The rate at which HIV-1 infected individuals progress to AIDS is highly variable and impacted by T cell immunity. CD8 T cell inhibitory molecules are up-regulated in HIV-1 infection and associate with immune dysfunction. We evaluated participants (n=122) recruited to the SPARTAC randomised clinical trial to determine whether CD8 T cell exhaustion markers PD-1, Lag-3 and Tim-3 were associated with immune activation and disease progression.Expression of PD-1, Tim-3, Lag-3 and CD38 on CD8 T cells from the closest pre-therapy time-point to seroconversion was measured by flow cytometry, and correlated with surrogate markers of HIV-1 disease (HIV-1 plasma viral load (pVL) and CD4 T cell count) and the trial endpoint (time to CD4 count <350 cells/μl or initiation of antiretroviral therapy). To explore the functional significance of these markers, co-expression of Eomes, T-bet and CD39 was assessed.Expression of PD-1 on CD8 and CD38 CD8 T cells correlated with pVL and CD4 count at baseline, and predicted time to the trial endpoint. Lag-3 expression was associated with pVL but not CD4 count. For all exhaustion markers, expression of CD38 on CD8 T cells increased the strength of associations. In Cox models, progression to the trial endpoint was most marked for PD-1/CD38 co-expressing cells, with evidence for a stronger effect within 12 weeks from confirmed diagnosis of PHI. The effect of PD-1 and Lag-3 expression on CD8 T cells retained statistical significance in Cox proportional hazards models including antiretroviral therapy and CD4 count, but not pVL as co-variants.Expression of ‘exhaustion’ or ‘immune checkpoint’ markers in early HIV-1 infection is associated with clinical progression and is impacted by immune activation and the duration of infection. New markers to identify exhausted T cells and novel interventions to reverse exhaustion may inform the development of novel immunotherapeutic approaches

ADHD in idiopathic epilepsy

Our aim was to clarify the correlation of attention deficit hyperactivity disorder (ADHD) with epilepsy and behavior problems. This was a cross-sectional study. Sixty children with idiopathic epilepsy were interviewed using the MTA-SNAP IV Teacher and Parent Rating Scale, Vineland Adaptive Behavior Scales and Conners’ Rating Scales. We used the chi-square test to analyze the correlation of epilepsy variables in patients with and without ADHD with a significance level of 0.05. Eight patients had ADHD symptoms (13%), seven had the inattentive ADHD subtype and only three had behavioral problems. When epileptic patients with and without ADHD symptoms were compared we found no significant difference in regard to epilepsy variables. All patients were controlled and 43% were either without AED or undergoing withdrawal. Our study revealed a low comorbidity of ADHD symptoms and epilepsy due to low interference of seizures and drug treatment on the comorbid condition

Products of cultured neuroglial cells: II. The production of fibronectin by C6 glioma cells

The possibility of fibronectin production by C6 glioma cells was examined with assays which require protein synthesis. Proteins produced by C6 cells using radiolabeled amino acid precursors were tested for affinity to collagen by binding to immobilized gelatin. The predominant collagen binding protein made by C6 coelectrophoresed with fibronectin synthesized by control fibroblasts and with the larger of the two proteins in unlabeled fibronectin when applied to polyacrylamide gels with sodium dodecyl sulfate (SDS). In addition, C6 produced a larger collagen binding protein of approximately 270,000 molecular weight. Solubilities in urea solutions of the collagen-binding proteins made by C6 cells and fibroblasts were similar. Immunofluorescence showed fibronectin associated with the C6 cell monolayer, but less abundant than the fibronectin associated with fibroblasts. Results provide evidence for the production of fibronectin by the C6 glioma cell line.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45400/1/11064_2004_Article_BF00964399.pd

Revisiting ‘place’ in a realist novel: ‘Thinking space’ in Galdós’s Torquemada en la hoguera (1889)

Departing from the premise that Galdós’s close engagement with space and place deserves to be at the forefront of scholarly attention, this article provides an in-depth study of their significance in Torquemada en la hoguera. It begins by analysing the relationship between the novel’s locations and the real world, demonstrating that the author codes the city of Madrid to express social concerns and promote reader engagement. It then proceeds to examine the public and private spheres, before highlighting the “place of the imagination” in the novel. It reveals that, as in Galdós’s press articles, reality is used as a springboard in Torquemada en la hoguera and, drawing upon recent theories, it posits that places serve as a framework for engaging readers with contemporary concerns and as an imaginative springboard for Galdós. They trigger what is effectively a “thinking space” for the author and it is through unravelling their significance that we can fully appreciate Galdós’s psychological sensitivity, the novel’s modernity, its symbolic value, and imaginative depth. The article concludes by proposing that Galdós’s works deserve to be re-examined as “Novels of the Geographical Imagination” and urges readers to revisit the significance of space and place therein