Elevated arsenic in Bengal Basin aquifers threatens human health. Most deep (>150 m) groundwater in Pleistocene aquifers is low in arsenic; however higher concentrations have been reported in the ...southwest border region. Here, we establish that this extensive arsenic contamination at depth is not associated with well failure. A combination of geochemistry and flow modeling constrains the factors that contribute to arsenic contamination at depth in this region. Deep groundwater in the affected area is younger (2.0 ± 0.6 kyr) than deep, low‐arsenic groundwater elsewhere (12.0 ± 4.0 kyr) based on radiocarbon. Stratigraphic data indicate pre‐Holocene deposition of the contaminated aquifers, but few low‐permeability strata. Numerical modeling indicates that this stratigraphic anomaly permits a natural flow system that transports shallow groundwater to depth. Thus, in areas lacking low‐permeability layers, arsenic contamination can occur in pre‐Holocene aquifers and is probably not an early sign of future deep contamination in regions with interbedded low‐permeability strata.
Plain Language Summary
Exposure to arsenic in untreated groundwater pumped from millions of shallow wells across rural South Asia causes life‐threatening cardiovascular disease and cancers in adults and reduces intellectual function in children. Deep (>150 m) groundwater low in arsenic is currently the most effective mitigation option in Bangladesh. This study shows that high concentrations of arsenic observed in deep aquifers in the border area between Bangladesh and India are likely confined to that region due to the absence of clay layers vertically dividing the sandy aquifer. Flow modeling constrained by groundwater dating shows that this contamination is therefore of natural origin and unlikely to expand to wider areas in the near future.
Key Points
Groundwater >150 m deep is contaminated with arsenic in a 100‐km‐long latitudinal transect across the southwestern Bengal Basin
Radiocarbon ages of deep groundwater are considerably lower in high‐As area compared to the rest of the basin
Modeling and analysis indicate that naturally deep flow in sand‐dominated stratigraphy likely causes younger ages and high As concentrations
We assessed whether a near-infrared spectroscopy (NIRS)-based algorithm for the personalized optimization of cerebral oxygenation during cardiopulmonary bypass combined with a restrictive red cell ...transfusion threshold would reduce perioperative injury to the brain, heart, and kidneys.
In a randomized controlled trial, participants in three UK centres were randomized with concealed allocation to a NIRS (INVOS 5100; Medtronic Inc., Minneapolis, MN, USA)-based ‘patient-specific’ algorithm that included a restrictive red cell transfusion threshold (haematocrit 18%) or to a ‘generic’ non-NIRS-based algorithm (standard care). The NIRS algorithm aimed to maintain cerebral oxygenation at an absolute value of > 50% or at > 70% of baseline values. The primary outcome for the trial was cognitive function measured up to 3 months postsurgery.
The analysis population comprised eligible randomized patients who underwent valve or combined valve surgery and coronary artery bypass grafts using cardiopulmonary bypass between December 2009 and January 2014 (n=98 patient-specific algorithm; n=106 generic algorithm). There was no difference between the groups for the three core cognitive domains (attention, verbal memory, and motor coordination) or for the non-core domains psychomotor speed and visuo-spatial skills. The NIRS group had higher scores for verbal fluency; mean difference 3.73 (95% confidence interval 1.50, 5.96). Red cell transfusions, biomarkers of brain, kidney, and myocardial injury, adverse events, and health-care costs were similar between the groups.
These results do not support the use of NIRS-based algorithms for the personalized optimization of cerebral oxygenation in adult cardiac surgery.
http://www.controlled-trials.com, ISRCTN 23557269.
Background: The Lung Cancer Cetuximab Study is an open-label, randomized phase II pilot study of cisplatin and vinorelbine combined with the epidermal growth factor receptor (EGFR)-targeted ...monoclonal antibody cetuximab versus cisplatin and vinorelbine alone, in patients with advanced EGFR-expressing, non-small-cell lung cancer (NSCLC). End points of the study are activity, safety and pharmacokinetics. Patients and methods: Following randomization, for a maximum of eight cycles, patients received three-weekly cycles of cisplatin (80 mg/m2, day 1) and vinorelbine (25 mg/m2 on days 1 and 8) alone or following cetuximab treatment (initial dose 400 mg/m2, followed by 250 mg/m2 weekly thereafter). Results: Eighty-six patients were randomly allocated to the study (43 per arm). Confirmed response rates were 28% in the cisplatin/vinorelbine arm (A) and 35% in the cetuximab plus cisplatin/vinorelbine arm (B). Median progression-free survival (PFS) was 4.6 months in arm A and 5.0 months in arm B, with PFS rates at 12 months of 0% and 15%, respectively. Median survival was 7.3 months in arm A and 8.3 months in arm B. The 24-month survival rates were 0% and 16%, respectively. The cetuximab combination was well tolerated. Conclusion: In the first-line treatment of advanced NSCLC, the combination of cetuximab plus cisplatin/vinorelbine demonstrated an acceptable safety profile and the potential to improve activity over cisplatin/vinorelbine alone.
In congenital mitochondrial DNA (mtDNA) disorders, a mixture of normal and mutated mtDNA (termed heteroplasmy) exists at varying levels in different tissues, which determines the severity and ...phenotypic expression of disease. Pearson marrow pancreas syndrome (PS) is a congenital bone marrow failure disorder caused by heteroplasmic deletions in mtDNA. The cause of the hematopoietic failure in PS is unknown, and adequate cellular and animal models are lacking. Induced pluripotent stem (iPS) cells are particularly amenable for studying mtDNA disorders, as cytoplasmic genetic material is retained during direct reprogramming. Here, we derive and characterize iPS cells from a patient with PS. Taking advantage of the tendency for heteroplasmy to change with cell passage, we isolated isogenic PS‐iPS cells without detectable levels of deleted mtDNA. We found that PS‐iPS cells carrying a high burden of deleted mtDNA displayed differences in growth, mitochondrial function, and hematopoietic phenotype when differentiated in vitro, compared to isogenic iPS cells without deleted mtDNA. Our results demonstrate that reprogramming somatic cells from patients with mtDNA disorders can yield pluripotent stem cells with varying burdens of heteroplasmy that might be useful in the study and treatment of mitochondrial diseases. STEM CELLS2013;31:1287–1297
Highbush blueberry (Vaccinium corymbosum L.; Ericales: Ericaceae) is an important crop grown throughout the eastern United States and Canada. Cross-pollination by insects greatly enhances pollination ...and fruit set in highbush blueberry. In Florida, low-chill cultivars that flower during the winter when most bees are dormant are used, thus, making it difficult to utilize and depend on unmanaged bees. We investigated flower visitation rates by managed and wild bees and the subsequent berry formation, berry weight, and number of seeds/berry in highbush blueberry fields in north-central Florida. Additionally, we tested three pollinator treatments: 1) pollinator-excluded flowers, 2) open-pollinated treatments that were available to managed and wild bees, and 3) flowers that were hand pollinated. Overall, we found seven native bee species that contribute to highbush blueberry pollination in Florida, but managed honey bees and bumble bees were the main flower visitors. Additionally, 14.5 times more blueberries formed in the open treatments than in the pollinator exclusion treatments, thus illustrating the economic impact bees have on blueberry pollination. Most of the wild bees observed visiting blueberry flowers were ground-nesting species that need uncultivated areas for nesting sites.Therefore, leaving field edges uncultivated and some undisturbed habitat may increase native bee numbers within blueberry farms over time.
IMPORTANCE: Specialist palliative care benefits patients undergoing medical treatment of cancer; however, data are lacking on whether patients undergoing surgery for cancer similarly benefit from ...specialist palliative care. OBJECTIVE: To determine the effect of a specialist palliative care intervention on patients undergoing surgery for cure or durable control of cancer. DESIGN, SETTING, AND PARTICIPANTS: This was a single-center randomized clinical trial conducted from March 1, 2018, to October 28, 2021. Patients scheduled for specified intra-abdominal cancer operations were recruited from an academic urban referral center in the Southeastern US. INTERVENTION: Preoperative consultation with palliative care specialists and postoperative inpatient and outpatient palliative care follow-up for 90 days. MAIN OUTCOMES AND MEASURES: The prespecified primary end point was physical and functional quality of life (QoL) at postoperative day (POD) 90, measured by the Functional Assessment of Cancer Therapy–General (FACT-G) Trial Outcome Index (TOI), which is scored on a range of 0 to 56 with higher scores representing higher physical and functional QoL. Prespecified secondary end points included overall QoL at POD 90 measured by FACT-G, days alive at home until POD 90, and 1-year overall survival. Multivariable proportional odds logistic regression and Cox proportional hazards regression models were used to test the hypothesis that the intervention improved each of these end points relative to usual care in an intention-to-treat analysis. RESULTS: A total of 235 eligible patients (median IQR age, 65.0 56.8-71.1 years; 141 male 60.0%) were randomly assigned to the intervention or usual care group in a 1:1 ratio. Specialist palliative care was received by 114 patients (97%) in the intervention group and 1 patient (1%) in the usual care group. Adjusted median scores on the FACT-G TOI measure of physical and functional QoL did not differ between groups (intervention score, 46.77; 95% CI, 44.18-49.04; usual care score, 46.23; 95% CI, 43.08-48.14; P = .46). Intervention vs usual care group odds ratio (OR) was 1.17 (95% CI, 0.77-1.80). Palliative care did not improve overall QoL measured by the FACT-G score (intervention vs usual care OR, 1.09; 95% CI, 0.75-1.58), days alive at home (OR, 0.87; 95% CI, 0.69-1.11), or 1-year overall survival (hazard ratio, 0.97; 95% CI, 0.50-1.88). CONCLUSIONS AND RELEVANCE: This randomized clinical trial showed no evidence that early specialist palliative care improves the QoL of patients undergoing nonpalliative cancer operations. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03436290
Across South Asia, millions of villagers have reduced their exposure to high‐arsenic (As) groundwater by switching to low‐As wells. Isotopic tracers and flow modeling are used in this study to ...understand the groundwater flow system of a semi‐confined aquifer of Pleistocene (>10 kyr) age in Bangladesh that is generally low in As but has been perturbed by massive pumping at a distance of about 25 km for the municipal water supply of Dhaka. A 10‐ to 15‐m‐thick clay aquitard caps much of the intermediate aquifer (>40‐ to 90‐m depth) in the 3‐km2 study area, with some interruptions by younger channel sand deposits indicative of river scouring. Hydraulic heads in the intermediate aquifer below the clay‐capped areas are 1–2 m lower than in the high‐As shallow aquifer above the clay layer. In contrast, similar heads in the shallow and intermediate aquifer are observed where the clay layer is missing. The head distribution suggests a pattern of downward flow through interruptions in the aquitard and lateral advection from the sandy areas to the confined portion of the aquifer. The interpreted flow system is consistent with 3H‐3He ages, stable isotope data, and groundwater flow modeling. Lateral flow could explain an association of elevated As with high methane concentrations within layers of gray sand below certain clay‐capped portions of the Pleistocene aquifer. An influx of dissolved organic carbon from the clay layer itself leading to a reduction of initially orange sands has also likely contributed to the rise of As.
Key Points
A clay‐capped Pleistocene aquifer under the influence of municipal pumping is contaminated with arsenic (As)
After pumping started, breaks in the clay aquitard became conduits for accelerated transport of tritium, As, and carbon from the shallow aquifer
Pumping induced transport of reactive carbon or arsenic emanating from the clay aquitard itself could lead to local release of As
Background:
The field of foot and ankle surgery lacks a widely accepted gold-standard patient-reported outcome instrument. With the changing infrastructure of the medical profession, more efficient ...patient-reported outcome tools are needed to reduce respondent burden and increase participation while providing consistent and reliable measurement across multiple pathologies and disciplines. The primary purpose of the present study was to validate 3 Patient-Reported Outcomes Measurement Information System computer adaptive tests (CATs) most relevant to the foot and ankle discipline against the Foot and Ankle Outcome Score (FAOS) and the Short Form 12 general health status survey in patients with 6 common foot and ankle pathologies.
Methods:
Patients (n = 240) indicated for operative treatment for 1 of 6 common foot and ankle pathologies completed the CATs, FAOS, and Short Form 12 at their preoperative surgical visits, 1 week subsequently (before surgery), and at 6 months postoperatively. The psychometric properties of the instruments were assessed and compared.
Results:
The Patient-Reported Outcomes Measurement Information System CATs each took less than 1 minute to complete, whereas the FAOS took 6.5 minutes, and the Short Form 12 took 3 minutes. CAT scores were more normally distributed and had fewer floor and ceiling effects than those on the FAOS, which reached as high as 24%. The CATs were more precise than the FAOS and had similar responsiveness and test-retest reliability. The physical function and mobility CATs correlated strongly with the activities subscale of the FAOS, and the pain interference CAT correlated strongly with the pain subscale of the FAOS. The CATs and FAOS were responsive to changes with operative treatment for 6 common foot and ankle pathologies.
Conclusions:
The CATs performed as well as or better than the FAOS in all aspects of psychometric validity. The Patient-Reported Outcomes Measurement Information System CATs show tremendous potential for improving the study of patient outcomes in foot and ankle research through improved precision and reduced respondent burden.
Level of Evidence:
Level II, prospective comparative study.
We define benchmark models for SUSY searches at the LHC, including the CMSSM, NUHM, mGMSB, mAMSB, MM-AMSB and p19MSSM, as well as models with R-parity violation and the NMSSM. Within the parameter ...spaces of these models, we propose benchmark subspaces, including planes, lines and points along them. The planes may be useful for presenting results of the experimental searches in different SUSY scenarios, while the specific benchmark points may serve for more detailed detector performance tests and comparisons. We also describe algorithms for defining suitable benchmark points along the proposed lines in the parameter spaces, and we define a few benchmark points motivated by recent fits to existing experimental data.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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