The Hamilton Watch Company is a Swiss manufacturer of wristwatches based in Bienne, Switzerland. The Hamilton Watch Company had its genesis as an American watch design and manufacturing company, which incorporated in 1892 and produced its first watch in 1893. After its formation, the Hamilton Watch Company went on to manufacture and market pocket watches and wristwatches, ending American manufacture in 1969. Through a series of mergers and acquisitions, the Hamilton Watch Company became a diversified conglomerate itself and was subsequently integrated into the Swatch Group. Today the brand is one of more than twenty watch brands belonging to the Swatch Group, the world's largest watch manufacturer and marketer.
OBJECTIVES:To perform an updated systematic review and meta-analysis of the efficacy and safety of intensive (INT) vs. conventional (CONV) blood glucose (BG) targets for critically ill adults on insulin infusions. DATA SOURCES:We conducted a comprehensive search of Embase and OVID Medline databases from inception to October 16, 2023. We manually excluded studies published before 2000 due to potential lack of relevance as glycemic control in the ICU was not routinely practiced before 2000. STUDY SELECTION:We included randomized controlled trials (RCTs) evaluating adult, critically ill patients on insulin infusions comparing INT vs. CONV targets for efficacy and safety outcomes. DATA EXTRACTION:Data were screened and extracted with accuracy confirmed by a second reviewer. Study methodological characteristics, patient population, interventions, and outcome data were recorded. Studies without numerical outcomes were summarized as text statements. DATA SYNTHESIS:Forty-five RCTs were included involving 32,215 patients. No differences were seen between INT and CONV targets for hospital mortality or ICU mortality. INT targets were associated with lower ICU length of stay (LOS), infections, and critical illness polyneuropathy (CIP); however, INT targets demonstrated a 3.6-fold higher risk of severe hypoglycemia. Most of the studies with significant differences contained serious inconsistencies or risk of bias. In the subgroup analyses, INT targets demonstrated favorable neurologic outcomes in neurologic ICU patients, lower ICU LOS in mixed ICU patients, and lower ICU mortality in the cardiac surgery subgroup. CONCLUSIONS:INT BG targets demonstrated mild to moderate improvements in several important morbidity secondary outcomes, including LOS, infections, and CIP, but were associated with a 3.6-fold higher risk of severe hypoglycemia. No differences were seen in ICU or hospital mortality. INT targets should not be routinely used over CONV targets when trying to minimize hypoglycemia as a marker of patient safety. However, as stated in the Society of Critical Care Medicine guidelines, a lower target within the INT range (110-140 mg/dL; 6.1-7.8 mmol/L) may be considered acceptable in select centers where the risk of hypoglycemia is documented to be negligible based on routine assessment and with the use of optimized glycemic management protocols.
ABSTRACT The Janzen‐Connell hypothesis proposed that conspecific negative density or distance dependence (CNDDD) helps maintain the species richness of tropical rainforests through the action of specialist natural enemies that suppress conspecific recruitment beneath canopy trees. Empirical studies have since shown that CNDDD occurs not only in tropical rainforests but in a wide range of other vegetation types. Studies of CNDDD have invariably focused on its implications for species coexistence and diversity; rarely has its potential relevance to successional replacement patterns been explored. Here we present evidence for CNDDD that may shed new light on a long‐standing problem in New Zealand forest dynamics—the failure of relatively shade‐tolerant conifers (in particular Dacrydium cupressinum , Podocarpaceae) to regenerate beneath their own canopies in dense podocarp stands. We mapped tree positions on a 3‐ha plot in a central North Island podocarp/broadleaf forest in which diameter distributions indicated two discrete cohorts of D. cupressinum trees and used pair‐correlation functions to measure hetero‐ and conspecific spatial associations between small and large trees. Small trees (5–60 cm diameter) of D. cupressinum were significantly negatively associated with large conspecific trees of the older cohort at radii of up to 7 m. This pattern cannot readily be explained by light requirements, as small trees of a less shade‐tolerant podocarp ( Phyllocladus trichomanoides ) were distributed independently of large D. cupressinum . Small trees of the only other species well‐represented by large diameters (the broadleaved species Elaeocarpus dentatus , Elaeocarpaceae) were also negatively associated with large conspecific trees, albeit across a narrower range of radii. Our results suggest CNDDD might contribute to the characteristic failure of D. cupressinum to regenerate in central North Island dense podocarp stands, regeneration resuming only when attrition or exogenous disturbance reduces the D. cupressinum overstorey to scattered emergent trees.
Introduction and Objective: The dangers of Type I diabetes stem from its potential to cause severe, long-term health complications affecting multiple organ systems. While islet transplantation is a viable clinical option, it remainsconstrained by limited donor availability and the requirement for lifelong immunosuppression. To overcome this challenge, we are developing synthetic hydrogels that physically protect transplanted cells from both allo and autoimmune attack, while allowing metabolic exchange. Allarta’s proprietary hydrogels have shown extended survival and function for primary rat as well as primary and stem cell-derived human islets, in vitro and in vivo. Building on these results, we are advancing toward a first-in-human clinical trial with donor islets. Methods: Islets derived from human donor pancreata, human pluripotent stem cells, and Wistar and Lewis rats were studied. Blood glucose and C-peptide of encapsulated islets were measured following implantation into streptozotocin (STZ)-induced diabetic immunocompromised and immunocompetent rodents. Viability and function were tested before implantation and after explantation. Further analyses included hydrogel diffusion limits and mechanical strength, and pericapsular overgrowth (PCO). Results: Protein exclusion could be fine-tuned to exclude IgG, while maintaining good cell viability and function after encapsulation. Encapsulated rat islets demonstrated rapid and sustained blood glucose control for weeks in mice and rats while the functionality of human donor and stem cell-derived islet could be extended in mice, as indicated by reduced blood glucose and increased C-peptide levels. Conclusion: Our proprietary, retrievable hydrogels showed strong immune protection for both allogenic and xenogeneic transplantation, without any immunosuppression. We are currently running CTA/FDA-enabling studies to prepare for a first-in-human clinical trial with donor-derived islets. Disclosure H. Stover: None. Funding JDRF (2-IND-2023-1449-I-X)
AIMS:Diabetes prevention programs (DPPs) that target the risk factors of type 2 diabetes (T2D) are critical for women with gestational diabetes mellitus (GDM). A new postpartum DPP developed in Toronto, Canada, has undergone successful pilot and feasibility testing. Preparation is now underway to implement this multi-centre DPP in Ontario, Canada. We aimed to explore the perspectives and preferences of women with GDM to inform program refinements and implementation strategy design for this DPP. METHODS:We used qualitative descriptive methods to elicit the perspectives of women with GDM regarding preferences for a postpartum DPP. The results of semi-structured interviews were analyzed using directed content analysis. We mapped the resulting findings to the Capability, Opportunity, Motivation - Behavior (COM-B) Model of Behavior Change. RESULTS:We identified three findings and six sub-findings that coincided with the components and sub-components of the COM-B Model of Behavior Change: (1) Capability-(a) physical and (b) psychological, balancing the ability to make behavior changes and the emotional impact of those changes; (2) Opportunity-(a) physical and (b) social, considering physical limitations of behavior changes and participating in a community of new mothers; and (3) Motivation-(a) reflexive and (b) automatic, examining the reasons for avoiding diabetes and understanding the correlation between diet, physical activity and well-being. CONCLUSIONS:Women with GDM desire the support of a DPP to avoid diabetes that considers their unique needs. A tailored approach that accounts for the capabilities, opportunities and motivations distinct to new mothers may optimize DPP uptake and engagement.
The endoplasmic reticulum (ER) has crucial roles in metabolically active cells, including protein translation, protein folding and quality control, lipid biosynthesis, and calcium homeostasis. Adverse metabolic conditions or pathogenic genetic variants that cause misfolding and accumulation of proteins within the ER of kidney cells initiate an injurious process known as ER stress that contributes to kidney disease and its cardiovascular complications. Initiation of ER stress activates the unfolded protein response (UPR), a cellular defence mechanism that functions to restore ER homeostasis. However, severe or chronic ER stress rewires the UPR to activate deleterious pathways that exacerbate inflammation, apoptosis and fibrosis, resulting in kidney injury. This insidious crosstalk between ER stress, UPR activation, oxidative stress and inflammation forms a vicious cycle that drives kidney disease and vascular damage. Furthermore, genetic variants that disrupt protein-folding mechanisms trigger ER stress, as evidenced in autosomal-dominant tubulointerstitial kidney disease and Fabry disease. Emerging therapeutic strategies that enhance protein-folding capacity and reduce the burden of ER stress have shown promising results in kidney diseases. Thus, integrating knowledge of how genetic variants cause protein misfolding and ER stress into clinical practice will enhance treatment strategies and potentially improve outcomes for various kidney diseases and their vascular complications. Endoplasmic reticulum (ER) stress is known to exacerbate chronic kidney disease and cardiovascular disease. Here, the authors discuss the role of ER stress in kidney disease and the link between ER stress, chronic kidney disease and cardiovascular disease.
