Seasonal water storage fluctuations are critical for evaluating water scarcity linked to climate forcing and human intervention. Here we compare seasonal changes in land total water storage anomalies ...using seven global hydrologic and land surface models (WGHM, PCR‐GLOBWB, and five GLDAS models) to GRACE satellite data in 183 river basins globally. This work builds on previous analysis that focused on total water storage anomaly trends. Results show that most models underestimate seasonal water storage amplitudes in tropical and (semi)arid basins and land surface models generally overestimate amplitudes in northern basins. Some models (CLM‐5.0 and PCR‐GLOBWB) agree better with GRACE than others. Causes of model‐GRACE discrepancies are attributed to missing storage compartments (e.g., surface water and/or groundwater) and underestimation of modeled storage capacities in tropical basins and to variations in modeled fluxes in northern basins. This study underscores the importance of considering water storage, in addition to water fluxes, to improve global models.
Plain Language Summary
We are relying more and more on global models to understand the water cycle, but we need to assess the reliability of model output. In this study we compare seasonal amplitudes in land total water storage from global models with those from GRACE satellite data in river basins globally. We found that seasonal amplitudes in total water storage account for more than half of the total signal, except in semiarid basins. Seasonal amplitudes are highest in tropical basins and lowest in semiarid basins. Some models agree better with GRACE than others (CLM‐5.0 and PCR‐GLOBWB). Most models underestimate GRACE‐derived seasonal amplitudes in tropical and semiarid basins but overestimate seasonal amplitudes in northern high latitude basins. The main cause of the discrepancies in tropical basins is likely insufficient storage capacity and lack of surface water inundation to accommodate the large seasonal storage variations. In northern high latitude basins, differences in snow physics and evapotranspiration increase seasonal amplitudes in water storage in newer versions of land surface models, overestimating GRACE‐derived seasonal amplitudes and reducing agreement with GRACE relative to earlier versions. Reliable models of seasonal variations in water storage are critical for assessing water scarcity, estimating response to climate extremes, and managing water resources.
Key Points
Modeled seasonal amplitudes are underestimated in tropical and semiarid basins and overestimated in northern basins relative to GRACE
Model‐GRACE discrepancies are attributed to insufficient storage capacities in tropical basins and biases in fluxes in northern basins
This study highlights the value of using water storage, in addition to traditional water flux, in assessing and improving global models
The objective of this field trial was to reduce bovine leukemia virus (BLV) transmission and prevalence in commercial dairy herds using proviral load (PVL) and lymphocyte count (LC) measurements as ...indicators of the most infectious animals for culling or segregation. Bovine leukemia virus causes lymphoma in <5% of infected cattle, and increased lymphocyte counts (lymphocytosis) in about one-third. Recent research has shown that dairy cows infected with BLV have altered immune function associated with decreases in milk production and lifespan. Recent findings show that a minority of infected cattle have PVL concentrations in blood and other body fluids of over 1,000 times that of other infected cattle. In combination with a high LC, these animals are thought to be responsible for most transmission of BLV in a herd. Milk or blood samples from adult cows in our 3 Midwestern dairy farm field trials were tested semiannually with ELISA for BLV antibodies, and ELISA-positive cattle were then retested using a blood LC and a quantitative PCR test for PVL to identify the animals presumed to be most infectious. Herd managers were encouraged to consider PVL and LC status when making cull decisions, and to segregate cows with the highest PVL and LC from their BLV ELISA-negative herd mates where possible. After 2 to 2.5 yr of this intervention, the incidence risk of new infections decreased in all 3 herds combined, from 13.8 to 2.2, and the overall herd prevalence decreased in all 3 herds combined from 62.0 to 20.7%, suggesting that this approach can efficiently reduce BLV transmission as well as prevalence. This is encouraging, because a very low prevalence of BLV infection would make it economically feasible to cull the remaining ELISA-positive cattle, as was achieved in national eradication programs in other countries decades ago.
Relative binding free energy (RBFE) calculations have emerged as a powerful tool that supports ligand optimization in drug discovery. Despite many successes, the use of RBFEs can often be limited by ...automation problems, in particular, the setup of such calculations. Atom mapping algorithms are an essential component in setting up automatic large-scale hybrid-topology RBFE calculation campaigns. Traditional algorithms typically employ a 2D subgraph isomorphism solver (SIS) in order to estimate the maximum common substructure. SIS-based approaches can be limited by time-intensive operations and issues with capturing geometry-linked chemical properties, potentially leading to suboptimal solutions. To overcome these limitations, we have developed Kartograf, a geometric-graph-based algorithm that uses primarily the 3D coordinates of atoms to find a mapping between two ligands. In free energy approaches, the ligand conformations are usually derived from docking or other previous modeling approaches, giving the coordinates a certain importance. By considering the spatial relationships between atoms related to the molecule coordinates, our algorithm bypasses the computationally complex subgraph matching of SIS-based approaches and reduces the problem to a much simpler bipartite graph matching problem. Moreover, Kartograf effectively circumvents typical mapping issues induced by molecule symmetry and stereoisomerism, making it a more robust approach for atom mapping from a geometric perspective. To validate our method, we calculated mappings with our novel approach using a diverse set of small molecules and used the mappings in relative hydration and binding free energy calculations. The comparison with two SIS-based algorithms showed that Kartograf offers a fast alternative approach. The code for Kartograf is freely available on GitHub (https://github.com/OpenFreeEnergy/kartograf). While developed for the OpenFE ecosystem, Kartograf can also be utilized as a standalone Python package.
Both postoperative epidural analgesia and intravenous (IV) infusion of local anesthetic have been shown to shorten ileus duration and hospital stay after colon surgery when compared with the use of ...systemic narcotics alone. However, they have not been compared directly with each other.
Prospective, randomized clinical trial was conducted comparing the 2 treatments in open colon surgery patients. Before induction of general anesthesia, patients were randomized either to epidural analgesia (bupivacaine 0.125% and hydromorphone 6 microg/mL were started at 10 mL/hr within 1 hr of the end of surgery) or IV lidocaine (1 mg/min in patients < 70 kg, 2 mg/min in patients > or = 70 kg). Markers of return of bowel function, length of stay, postoperative pain scores, systemic analgesic requirements, and adverse events were recorded and compared between the 2 groups in an intent-to-treat analysis.
Study enrollment took place from April 2005 to July 2006. Twenty-two patients were randomized to IV lidocaine therapy and 20 patients to epidural therapy. No statistically significant differences were found between groups in time to return of bowel function or hospital length of stay. The median pain score difference was not statistically significant. No statistically significant differences were found in pain scores for any specific postoperative day or in analgesic consumption.
No differences were observed between groups in terms of return of bowel function, duration of hospital stay, and postoperative pain control, suggesting that IV infusion of local anesthetic may be an effective alternative to epidural therapy in patients in whom epidural anesthesia is contraindicated or not desired.
: Background. Diarrhea in solid organ transplantation can be a complication with a high morbidity and mortality. Rotavirus (RV) infection normally occurs in children up to 3 years of age and often ...presents with severe diarrhea; however, it can also affect adults. We investigated the prevalence and outcome of RV infections in both adult and pediatric patients after solid organ transplantation.
Patients and methods. Retrospective analysis of RV‐related enteritis in solid organ transplant recipients with a minimum of a 1‐year follow‐up from a single center between 2000 and 2004.
Results. Within our cohort of 1303 solid organ transplants, RV infection was observed in 19 patients (1.5%); 14 of these were liver recipients. Infection was most prevalent among pediatric liver recipients, with 52% (11/21) of the children affected. Five adults acquired the infection during their initial hospitalization. Two adult patients had to be readmitted following late‐onset RV infection. In all cases, infection was self‐limiting, but led to prolonged hospitalization because of significant loss of fluids and electrolytes.
Conclusions. RV enteritis is a common infection in pediatric solid organ recipients but may also affect adult patients.
Objective:
The goal is to evaluate avelumab, an anti-PD-L1 monoclonal immunoglobulin G antibody labeled with zirconium-89 in human PD-L1-expressing cancer cells and mouse xenografts for clinical ...translation.
Methods:
89ZrZr-DFO-PD-L1 monoclonal antibody (mAb) was synthesized using avelumab conjugated to desferrioxamine. In vitro binding studies and biodistribution studies were performed with PD-L1+MDA-MB231 cells and MDA-MB231 xenograft mouse models, respectively. Biodistributions were determined at 1, 2, 3, 5, and 7 days post coinjection of 89ZrZr-DFO-PD-L1 mAb without or with unlabeled avelumab (10, 20, 40, and 400 µg).
Results:
89ZrZr-DFO-PD-L1 mAb exhibited high affinity (Kd ∼ 0.3 nM) and detected moderate PD-L1 expression levels in MDA-MB231 cells. The spleen and lymph nodes exhibited the highest 89ZrZr-DFO-PD-L1 mAb uptakes in all time points, while MDA-MB231 tumor uptakes were lower but highly retained. In the unlabeled avelumab dose escalation studies, spleen tissue–muscle ratios decreased in a dose-dependent manner indicating specific 89ZrZr-DFO-PD-L1 mAb binding to PD-L1. In contrast, lymph node and tumor tissue–muscle ratios increased 4- to 5-fold at 20 and 40 µg avelumab doses.
Conclusions:
89ZrZr-DFO-PD-L1 mAb exhibited specific and high affinity for PD-L1 in vitro and had target tissue uptakes correlating with PD-L1 expression levels in vivo. 89ZrZr-DFO-PD-L1 mAb uptake in PD-L1+tumors increased with escalating doses of avelumab.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
: Combined kidney–pancreas transplantation is the treatment of choice for end‐stage diabetic nephropathy. Post‐transplant weight gain increases the risk for post‐transplant complications and death ...owing to cardiovascular events. Gastric banding is an established treatment for moderate morbid obesity. We report on a patient who experienced significant weight gain and developed type II diabetes mellitus following successful kidney–pancreas transplantation. He underwent laparoscopic gastric banding and initially had good weight loss. However, lack of compliance with dietary guidelines led to transient failure of weight loss therapy. With further adjustment of the gastric band good weight loss was achieved.
E. R. Swenson, T. B. Duncan, S. V. Goldberg, G. Ramirez, S. Ahmad and R. B. Schoene
Medical Service, Veterans Affairs Medical Center, Seattle, Washington, USA.
Acute hypoxia causes increased sodium ...and water excretion. Animal studies
suggest that this renal response is largely driven by direct peripheral
arterial chemoreceptor stimulation, independent of accompanying changes in
ventilation and acid-base status. Whether the diuresis and natriuresis
observed in humans made acutely hypoxic are caused by peripheral
chemoreceptor stimulation is not known, but, if so, we hypothesized that
people with a high ventilatory response to hypoxia (high peripheral
chemosensitivity) should have greater diuresis and natriuresis than those
with a low ventilatory response to hypoxia. The isocapnic hypoxic
ventilatory response (HVR) of 16 subjects on a fixed sodium intake was
measured, as were their urinary volume and sodium and bicarbonate losses
during 6 h of breathing air (in a normobaric environmental chamber) and, on
the subsequent day, 12% O2. The isocapnic HVR correlated positively with
hypoxic diuresis (r = 0.87) and natriuresis (r = 0.76). In contrast, the
isocapnic HVR did not correlate with bicarbonate excretion, despite the
expected respiratory alkalosis of acute hypoxia. The magnitude of diuresis
and natriuresis with hypoxia did not correlate with changes in circulating
aldosterone, renin, atrial natriuretic peptide, vasopressin, or a
digoxin-like immunoreactive substance. These findings are compatible with a
role of the peripheral arterial chemoreceptors in mediating the renal
response to hypoxia in humans. The efferent pathway remains unknown.
Background Anal abscesses are commonly associated with fistulas‐in‐ano and are usually polymicrobial in nature, with gram‐negative rods and anaerobes being the most prevalent isolates. Group Milleri ...Streptococci (GMS) comprise a heterogeneous group of cocci, which are capable of causing severe purulent infection with a high recurrence rate.
Method All anorectal infections caused by GMS, which were identified at our centre during a 4‐year period were retrospectively analysed. The 18 patients with GMS‐positive anorectal abscesses were matched with 36 GMS‐negative anorectal abscesses to identify outcome characteristics of this clinical entity.
Results During the study period, 358 patients underwent surgical treatment for anal infections; GMS were isolated in 46 individuals (13%) including 18 perianal abscesses, 11 pilonidal sinuses, eight fistulae in and nine miscellaneous infections. Seventy‐two per cent of perianal GMS infections were polymicrobial with E. coli and Bacteroides fragilis being the predominant second bacteria. Nine patients (20%) developed recurrent abscesses and fistulae‐in‐ano and underwent additional surgical interventions with resolution at follow‐up. Additional antibiotic treatment was administered in 10 patients with complex anal infections. Matched pair analysis revealed that GMS‐positive perianal abscesses were more commonly polymicrobial, and that the recurrence rate was higher (55.6% GMS‐positive and 22.2% GMS‐negative patients, P = 0.017).
Conclusions Our data confirm the propensity of GMS to form deep and recurrent abscesses with a higher recurrence rate than non‐GMS infections. First‐line treatment includes surgical drainage, and antibiotic treatment may be useful in selected patients.
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