During cluster investigation, index patients name social contacts that are not sex or drug-sharing partners. The likelihood of identifying new HIV infections among social contacts is unknown. We ...hypothesized greater odds of identifying new infections among social contacts identified by men who report sex with men (MSM). We reviewed North Carolina HIV diagnoses during 2002–2005 and used logistic regression to compare testing results among social contacts of MSM, men who report sex with women only (MSW) and women. HIV was newly diagnosed among 54/601 (9.0 %) social contacts tested named by MSM, 16/522 (3.1 %) named by MSW, and 23/639 (3.6 %) named by women. Compared with those named by MSW, odds of new HIV diagnosis were greater among MSM social contacts (adjusted odds ratio: 2.5; 95 % confidence interval: 1.3–4.7). Testing social contacts identified previously undiagnosed HIV infections and could provide an opportunity to interrupt transmission.
Tracking human immunodeficiency virus-type 1 (HIV-1) infection at the cellular level in tissue reservoirs provides opportunities to better understand the pathogenesis of infection and to rationally ...design and monitor therapy A quantitative technique was developed to determine viral burden in two important cellular compartments in lymphoid tissues. Image analysis and in situ hybridization were combined to show that in the presymptomatic stages of infection there is a large, relatively stable pool of virions on the surfaces of follicular dendritic cells and a smaller pool of productively infected cells Despite evidence of constraints on HIV-1 replication in the infected cell population in lymphoid tissues, estimates of the numbers of these cells and the virus they could produce are consistent with the quantities of virus that have been detected in the bloodstream. The cellular sources of virus production and storage in lymphoid tissues can now be studied with this approach over the course of infection and treatment.
Bacterial blood stream infections (BSI) are a common cause of mortality and morbidity globally. As the causative agents and the resulting treatment decisions vary, near-patient testing and ...surveillance tools are necessary to monitor bacterial causes and resistance to antimicrobial agents. The gold standard to identify BSIs is blood culture (BC), a methodology not widely available in resource-limited settings. The aim of the study was to map out a target product profile of a simplified BC system (SBCS) to inform product development efforts. To identify the desired characteristics of a SBCS, we enlisted a small group of specialists working in Africa and Asia. Questions were used to understand challenges and how these constraints inform system requirements. The specialists were infectious disease physicians, public health/clinical microbiologists, clinical researchers, and technology experts with different geographical backgrounds. All suggested that BC should ideally be available at the district hospital level. Many of the same operational challenges, such as limited availability of culture bottles, electricity and internet connectivity, profuse dust, the lack of ambient temperature control, and human capacity constraints were identified across the different regions. BCs, although the accepted gold standard for diagnosis of BSIs, are not widely available outside of reference/research centers in Africa and Asia. To extend the reach of this important tool, it is crucial to engage product developers and academic research partners to develop accessible alternatives.
Continuous observations are an accurate method for behavioral measurements but are difficult to conduct on large numbers of animals because of extensive labor requirements. Thus, we sought to develop ...methods of behavioral data collection in feedlot cattle production systems that reasonably approximated continuous sampling. Standing, lying, feeding, drinking, and walking behaviors were examined from 224 h of continuous video from 64 heifers. Experiment 1 (n = 24 heifers) compared continuous behavioral sampling techniques (Continuous) with scan sampling using intervals of 1, 5, 10, 15, 30, and 60 min and time sampling (a technique for the periodic recording of behavior) for the first 10 min out of every 60 min. Means for each scan sampling method did not differ in estimated percentage of duration of behaviors (P > 0.05) from continuous sampling, except for scan sampling with a 60-min interval. Scan sampling with a 60-min interval differed from more frequent scan sampling intervals for all behaviors except lying. Scan sampling with short intervals (1 and 5 min) was correlated highly with Continuous for all behaviors. The longer the scan interval, the lower the correlations, especially for behaviors with short duration. Time sampling was not an accurate technique for measuring the sampled behaviors. Focal animal sampling (using continuous sampling of individuals) indicated that one heifer was representative of the entire pen of 10 animals (Continuous) for all maintenance behaviors except drinking. Scan sampling methods (1-, 5-, 10-, and 15-min intervals) were accurate methods of behavioral sampling for feedlot cattle, but scan intervals of 30 or 60 min were less accurate and less precise. Time sampling was not an accurate method because it overestimated standing and underestimated lying behaviors. Experiment 2 (n = 40 heifers) investigated the number of focal animals required to accurately represent continuous behavioral sampling for all animals. Focal animal sampling was accurate for most behaviors using as few as 1 animal out of 10 but was not an accurate method for drinking behavior unless 40% of the animals in the pen were observed. Estimates of sample sizes needed for experimental protocols are provided. Behavioral means, standard deviations, and coefficients of variation are presented along with estimates of required sample sizes. These results validate accurate, precise, and efficient methods for quantifying feedlot cattle behavior.
Nutrient availability influences intestinal epithelial stem cell proliferation and tissue growth. Increases in food result in a greater number of epithelial cells, villi height and crypt depth. We ...investigated whether this nutrient-driven expansion of the tissue is the result of a change in the mode of intestinal epithelial stem cell division and if LKB1-AMPK signaling plays a role. We utilized in vivo and in vitro experiments to test this hypothesis. C57BL/6J mice were separated into four groups and fed varying amounts of chow for 18 h: (1) ad libitum, (2) 50% of their average daily intake (3) fasted or (4) fasted for 12 h and refed. Mice were sacrificed, intestinal sections excised and immunohistochemically processed to determine the mitotic spindle orientation. Epithelial organoids in vitro were treated with no (0 mM), low (5 mM) or high (20 mM) amounts of glucose with or without an activator (Metformin) or inhibitor (Compound C) of LKB1-AMPK signaling. Cells were then processed to determine the mode of stem cell division. Fasted mice show a greater % of asymmetrically dividing cells compared with the other feeding groups. Organoids incubated with 0 mM glucose resulted in a greater % of asymmetrically dividing cells compared with the low or high-glucose conditions. In addition, LKB1-AMPK activation attenuated the % of symmetric division normally seen in high-glucose conditions. In contrast, LKB1-AMPK inhibition attenuated the % of asymmetric division normally seen in no glucose conditions. These data suggest that nutrient availability dictates the mode of division and that LKB1-AMPK mediates this nutrient-driven effect on intestinal epithelial stem cell proliferation.
Impact statement
The underlying cell biology of changes in the polarity of mitotic spindles and its relevance to tissue growth is a new concept and, thus, these data provide novel findings to begin to explain how this process contributes to the regeneration and growth of tissues. We find that short-term changes in food intake in vivo or glucose availability in vitro dictate the mode of division of crypt cells. In addition, we find that LKB1-AMPK signaling modulates the glucose-induced changes in the mode of division in vitro. Identifying mechanisms involved in the mode of division may provide new targets to control tissue growth.
Background and objectives
Outpatient parenteral antimicrobial therapy (OPAT) for infections has been in use for nearly 40 years, and although it has been found safe and efficacious, its use has been ...studied primarily among otherwise healthy patients. We aimed to develop and evaluate an OPAT program for patients with cancer, particularly solid tumors.
Methods
We implemented multiple quality improvement interventions between June 2018 and January 2020. We retrospectively and prospectively collected data on demographics, the completeness of infectious diseases (ID) physician consultation notes, rates of laboratory test result monitoring, ID clinic follow-up, and 30-day outcomes, including unplanned OPAT-related readmissions, OPAT-related emergency center visits, and deaths.
Results
Completeness of ID provider notes improved from a baseline of 77 to 100% (
p
< .0001) for antimicrobial recommendations, 75 to 97% (
p
< .0001) for follow-up recommendations, and 19 to 98% (
p
< .0001) for laboratory test result monitoring recommendations. Completion of laboratory tests increased from a baseline rate of 24 to 56% (
p
= .027). Thirty-day unplanned OPAT-related readmission, ID clinic follow-up, 30-day emergency center visit, and death rates improved without reaching statistical significance.
Conclusions
Sustained efforts, multiple interventions, and multidisciplinary engagement can improve laboratory test result monitoring among solid tumor patients discharged with OPAT. Although demonstrating a decrease in unplanned readmissions through institution of a formal OPAT program among patients with solid malignancies may be more difficult compared with the general population, the program may still result in improved safety.
The intestinal epithelium plays an essential role in nutrient absorption, hormone release, and barrier function. Maintenance of the epithelium is driven by continuous cell renewal by intestinal ...epithelial stem cells located in the intestinal crypts. Obesity affects this process and results in changes in the size and function of the tissue. Because both the amount of food intake and the composition of the diet are contributing factors to developing and maintaining obesity, it is necessary to tease apart the separate contributions of obesity versus the type/amount of diet in driving the epithelial changes. C57BL/6J mice were fed a 60% high-fat diet versus a 10% low-fat diet for three months. A pair fed group was included (mice were fed with high-fat diet, but in equal kcal as that eaten by the low-fat diet- fed mice to keep them lean). We investigated the differences in (1) crypt-villus morphology in vivo, (2) the number and function of differentiated epithelial cell types in vivo, and (3) lasting effects on intestinal epithelial stem cell proliferation and growth in vitro. We found that high-fat diet-induced obesity, independent of the high-fat diet, increased crypt depth, villus height, the number of intestinal epithelial stem cells and goblet cells in vivo, and enhanced the size of the enterospheres developed from isolated IESCs in vitro. In addition, there is an interaction of obesity, type of diet, and availability of the diet (pair fed versus ad libitum) on protein and mRNA expression of alkaline phosphatase (an enzyme of enterocytes). These results suggest that high-fat diet-induced obesity, independent of the high-fat diet, induces lasting effects on intestinal epithelial stem cell proliferation, and drives the differentiation into goblet cells, but an interaction of obesity and diet drives alterations in the function of the enterocytes.
Impact statement
This study investigates whether obesity or the type/amount of diet differentially alters the proliferation, differentiation, growth, and function of the intestinal epithelial tissue. Although diet-induced obesity is known to alter the growth and function of the epithelium in vivo and cause lasting effects in intestinal epithelial stem cells (IESCs) in vitro, we are the first to tease apart the separate contributions of obesity versus the type/amount of diet in these processes. We found that high-fat diet (HFD)-induced obesity, independent of the HFD, drives lasting effects on IESC proliferation and differentiation into goblet cells, which may contribute to the growth of the epithelium. In addition, there is an interaction of obesity, type of diet, and availability of the diet (PF versus ad libitum) on the function of enterocytes. Identification of the factors driving the epithelial changes may provide new therapeutic strategies to control altered tissue growth and function associated with obesity.
One hundred twelve crossbred feedlot heifers were used in two experiments to assess the impact of heat stress and its relief by shade and(or) water misting on behavior, physiology, performance, and ...carcass traits. Treatments were 1) no shading or misting (CONT); 2) only misting (MIST); 3) only shading (SHADE); and 4) shading plus misting (SHMI). Head in the feed bunk, head in or above the waterer, walking, standing, and lying behaviors were observed. Rectal temperature, respiration rate, and carcass traits were measured, as well as DMI, ADG, and feed:gain. Dietary NEm and NEg concentrations were calculated from performance data. In Exp. 1, (32 heifers; average BW 288 kg) the CONT heifers spent more time lying down than all others (P < 0.01). In addition, CONT heifers spent less time (P < 0.01) standing than SHADE and MIST heifers. Misting decreased (P < 0.01) rectal temperature and MIST as well as SHADE lowered (P < 0.05) respiration rates. In Exp. 2 (80 heifers; average BW = 336 kg), lying and walking behaviors did not differ among treatments, but shade increased (P < 0.01) standing behavior in heifers. The MIST cattle performed less (P < 0.05) head-above-water behavior than unmisted cattle. Rectal temperatures did not differ among treatments, but respiration rate was lower in shaded than in unshaded heifers (P < 0.05). Shaded compared with unshaded heifers had greater DMI (9.46 vs 8.80 +/- 0.14 kg/d, P < 0.01) and ADG (1.6 vs 1.41 +/- 0.1 kg/d, P < 0.01). Heifers provided with shade reached their target BW 20 d earlier than the unshaded heifers and differed in final BW (547 vs 520 +/- 6 kg, P < 0.01). Feed:gain and calculated NEg and NEm concentrations did not differ among treatments, and carcass traits were generally similar among treatments. In conclusion, cattle without shade had a physiological and behavioral stress response to heat that negatively affected productivity. Providing shade for beef cattle was a suitable solution to decrease heat stress and to lower the negative effects of heat on performance, whereas misting was largely ineffective.
In this paper, the coupled-mode equations for sum-frequency generation (SFG) and difference-frequency generation (DFG) driven by multiple pumps are solved, and the noise figures of idler generation ...are determined. For SFG, the (common) noise figure is n, the number of pumps (and idlers), whereas for DFG, the (common) noise figure is 2, independent of n. Thus, DFG driven by multiple pumps enables the generation of multiple low-noise idlers.
Let R be a commutative Noetherian ring and E the minimal injective cogenerator of the category of R-modules. An R-module M is (Matlis) reflexive if the natural evaluation map M\to \mathrm ...{Hom}_R(\mathrm {Hom}_R(M,E),E) is an isomorphism. We prove that if S is a multiplicatively closed subset of R and M is an R_S-module which is reflexive as an R-module, then M is a reflexive R_S-module. The converse holds when S is the complement of the union of finitely many nonminimal primes of R, but fails in general.
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