Individuality and slow dynamics in bacterial growth homeostasis

Microbial growth and division are fundamental processes relevant to many areas of life science. Of particular interest are homeostasis mechanisms, which buffer growth and division from accumulating fluctuations over multiple cycles. These mechanisms operate within single cells, possibly extending over several division cycles. However, all experimental studies to date have relied on measurements pooled from many distinct cells. Here, we disentangle long-term measured traces of individual cells from one another, revealing subtle differences between temporal and pooled statistics. By analyzing correlations along up to hundreds of generations, we find that the parameter describing effective cell-size homeostasis strength varies significantly among cells. At the same time, we find an invariant cell size which acts as an attractor to all individual traces, albeit with different effective attractive forces. Despite the common attractor, each cell maintains a distinct average size over its finite lifetime with suppressed temporal fluctuations around it, and equilibration to the global average size is surprisingly slow (> 150 cell cycles). To demonstrate a possible source of variable homeostasis strength, we construct a mathematical model relying on intracellular interactions, which integrates measured properties of cell size with those of highly expressed proteins. Effective homeostasis strength is then influenced by interactions and by noise levels, and generally varies among cells. A predictable and measurable consequence of variable homeostasis strength appears as distinct oscillatory patterns in cell size and protein content over many generations. We discuss the implications of our results to understanding mechanisms controlling division in single cells and their characteristic timescalesComment: In press with PNAS. 50 pages, including supplementary informatio

Update of the ICUD-SIU consultation on upper tract urothelial carcinoma 2016: treatment of low-risk upper tract urothelial carcinoma

Introduction The conservative management of upper tract urothelial carcinoma (UTUC) has historically been offered to patients with imperative indications. The recent International Consultation on Urologic Diseases (ICUD) publication on UTUC stratified treatment allocations based on high- and low-risk groups. This report updates the conservative management of the low-risk group. Methods The ICUD for low-risk UTUC working group performed a thorough review of the literature with an assessment of the level of evidence and grade of recommendation for a variety of published studies in this disease space. We update these publications and provide a summary of that original report. Results There are no prospective randomized controlled studies to support surgical management guidelines. A risk-stratified approach based on clinical, endoscopic, and biopsy assessment allows selection of patients who could benefit from kidney-preserving procedures with oncological outcomes potentially similar to radical nephroureterectomy with bladder cuff excision, with the added benefit of renal function preservation. These treatments are aided by the development of high-definition flexible digital URS, multi-biopsies with the aid of access sheaths and other tools, and promising developments in the use of adjuvant topical therapy. Conclusions Recent developments in imaging, minimally invasive techniques, multimodality approaches, and adjuvant topical regimens and bladder cancer prevention raise the hope for improved risk stratification and may greatly improve the endoscopic treatment for low-risk UTUC

Taking stock of 10 years of published research on the ASHA programme: Examining India’s national community health worker programme from a health systems perspective

Background: As India’s accredited social health activist (ASHA) community health worker (CHW) programme enters its second decade, we take stock of the research undertaken and whether it examines the health systems interfaces required to sustain the programme at scale. Methods: We systematically searched three databases for articles on ASHAs published between 2005 and 2016. Articles that met the inclusion criteria underwent analysis using an inductive CHW–health systems interface framework. Results: A total of 122 academic articles were identified (56 quantitative, 29 mixed methods, 28 qualitative, and 9 commentary or synthesis); 44 articles reported on special interventions and 78 on the routine ASHA program. Findings on special interventions were overwhelmingly positive, with few negative or mixed results. In contrast, 55% of articles on the routine ASHA programme showed mixed findings and 23% negative, with few indicating overall positive findings, reflecting broader system constraints. Over half the articles had a health system perspective, including almost all those on general ASHA work, but only a third of those with a health condition focus. The most extensively researched health systems topics were ASHA performance, training and capacity-building, with very little research done on programme financing and reporting, ASHA grievance redressal or peer communication. Research tended to be descriptive, with fewer influence, explanatory or exploratory articles, and no predictive or emancipatory studies. Indian institutions and authors led and partnered on most of the research, wrote all the critical commentaries, and published more studies with negative results. Conclusion: Published work on ASHAs highlights a range of small-scale innovations, but also showcases the challenges faced by a programme at massive scale, situated in the broader health system. As the programme continues to evolve, critical comparative research that constructively feeds back into programme reforms is needed, particularly related to governance, intersectoral linkages, ASHA solidarity, and community capacity to provide support and oversight

Dialysis Modality and Correction of Uremic Metabolic Acidosis: Relationship with All-Cause and Cause-Specific Mortality

BACKGROUND AND OBJECTIVES: Uremic metabolic acidosis is only partially corrected in many hemodialysis patients, and low serum bicarbonate predicts higher death risk. This study determined the comparative efficacy of peritoneal dialysis in correcting uremic metabolic acidosis and the association of serum bicarbonate and death risk with the two therapies. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Data were obtained from 121,351 prevalent ESRD patients (peritoneal dialysis, 10,400; hemodialysis, 110,951) treated in DaVita facilities between July 1, 2001 and June 30, 2006, with follow-up through June of 2007. RESULTS: Serum bicarbonate was <22 mEq/L in 25% and 40% of peritoneal dialysis and hemodialysis patients, respectively. Thus, peritoneal dialysis patients were substantially less likely to have lower serum bicarbonate (adjusted odds ratio<20 mEq/L, 0.45 [0.42, 0.49]; <22 mEq/L, 0.41 [0.39, 0.43]). Time-averaged serum bicarbonate<19 mEq/L was associated with an 18% and 25% higher risk for all-cause and cardiovascular mortality, respectively, in prevalent peritoneal dialysis patients (reference group: serum bicarbonate between 24 and <25 mEq/L). In analyses using the entire cohort of peritoneal dialysis and hemodialysis patients, the adjusted risk for all-cause mortality was higher in most subgroups with serum bicarbonate<22 mEq/L, irrespective of dialysis modality. CONCLUSIONS: The measured bicarbonate is significantly higher in peritoneal dialysis patients, suggesting that the therapy provides a more complete correction of metabolic acidosis than intermittent hemodialysis. Survival data suggest maintaining serum bicarbonate>22 mEq/L for all ESRD patients, irrespective of dialysis modality

A Panda fiber temperature sensor up to 900°C

Publisher Copyright: © 2022 The Author(s).The use of Panda-type polarization-maintaining (PM) fiber for the localized sensing of high temperatures was analyzed with simulations and experiments up to 900°C. Accuracy and repeatability of the results started to decline above 800°C. Fused silica optical fiber melts at 1700°C, which sets an ultimate limit for measurable temperatures. In practice, optical fiber birefringence restricts the maximum temperature to 1060°C where PM fiber loses its ability to maintain polarization. Three sensor fibers (4, 5 and 10 cm long) were spliced at 45° angles to input/output fibers and calibrated in an oven from room temperature to 850-900°C temperature range. Two superluminescent light-emitting diodes (SLEDs) were coupled together as a broadband light source. Birefringence-induced change of the polarization in the sensor fiber was measured with a polarization splitter and an optical spectrum analyzer (OSA) as a function of the wavelength. Temperature-dependent birefringence generates a sinusoidal reflection spectrum fromthe input polarization mode to the orthogonal output polarization mode. Temperature changes could be concluded from variations in these spectra. Finally, a small fusion device, NORTH, at DTU, Denmark was successfully used as a testbed to make sure that the sensors can handle transportation and the instrumentation required for vacuum operation and still produce sensible data from a harsh environment.Peer reviewe