A Failure of Imagination

In the wake of increased behavioral issues in the peri- and post-COVID environment, schools have resorted to zero-tolerance policies that imposed uniform and predetermined punishments for even the slightest infraction. In this article, the authors argue that these policies represent a failure of imagination that installs punitive policies that do more harm than good. Further, they suggest that restorative justice and/or school-wide positive behavior support systems are better means of creating educational environments in which all students flourish

Effect of Transmission Reduction by Insecticide-Treated Bednets (ITNs) on Antimalarial Drug Resistance in Western Kenya

Despite the clear public health benefit of insecticide-treated bednets (ITNs), the impact of malaria transmission-reduction by vector control on the spread of drug resistance is not well understood. In the present study, the effect of sustained transmission reduction by ITNs on the prevalence of Plasmodium falciparum gene mutations associated with resistance to the antimalarial drugs sulfadoxine-pyrimethamine (SP) and chloroquine (CQ) in children under the age of five years was investigated during an ITN trial in Asembo area, western Kenya. During the ITN trial, the national first line antimalarial treatment changed from CQ to SP. Smear-positive samples collected from cross sectional surveys prior to ITN introduction (baseline, n = 250) and five years post-ITN intervention (year 5 survey, n = 242) were genotyped for single nucleotide polymorphisms (SNPs) at dhfr-51, 59, 108, 164 and dhps-437, 540 (SP resistance), and pfcrt-76 and pfmdr1-86 (CQ resistance). The association between the drug resistance mutations and epidemiological variables was evaluated. There were significant increases in the prevalence of SP dhps mutations and the dhfr/dhps quintuple mutant, and a significant reduction in the proportion of mixed infections detected at dhfr-51, 59 and dhps-437, 540 SNPs from baseline to the year 5 survey. There was no change in the high prevalence of pfcrt-76 and pfmdr1-86 mutations. Multivariable regression analysis further showed that current antifolate use and year of survey were significantly associated with more SP drug resistance mutations. These results suggest that increased antifolate drug use due to drug policy change likely led to the high prevalence of SP mutations 5 years post-ITN intervention and reduced transmission had no apparent effect on the existing high prevalence of CQ mutations. There is no evidence from the current study that sustained transmission reduction by ITNs reduces the prevalence of genes associated with malaria drug resistance

A Two-cohort Phase I Study of Weekly Oxaliplatin and Gemcitabine, Then Oxaliplatin, Gemcitabine, and Erlotinib During Radiotherapy for Unresectable Pancreatic Carcinoma

Gemcitabine is a potent radiosensitizer. When combined with standard radiotherapy (XRT) the gemcitabine dose must be reduced to about 10% of its conventional dose. Oxaliplatin and erlotinib also have radiosensitizing properties. In vitro, oxaliplatin and gemcitabine have demonstrated synergy. We aimed to determine the maximum tolerated dose of oxaliplatin and gemcitabine with concurrent XRT, then oxaliplatin, gemcitaibine and erlotinib with XRT in the treatment of locally advanced and low volume metastatic pancreatic or biliary cancer

A Phase II Trial of Gemcitabine, 5-Florouracil, and Radiation Therapy in Locally Advanced Non-Metastatic Pancreatic Adenocarcinoma: Cancer and Leukemia Group B (CALGB) 80003

To assess the efficacy and safety of 5-fluorouracil (5FU) and gemcitabine administered concurrently with radiation in patients with locally advanced, non-metastatic pancreatic cancer

Water quality is a poor predictor of recreational hotspots in England

Maintaining and improving water quality is key to the protection and restoration of aquatic ecosystems, which provide important benefits to society. In Europe, the Water Framework Directive (WFD) defines water quality based on a set of biological, hydro-morphological and chemical targets, and aims to reach good quality conditions in all river bodies by the year 2027. While recently it has been argued that achieving these goals will deliver and enhance ecosystem services, in particular recreational services, there is little empirical evidence demonstrating so. Here we test the hypothesis that good water quality is associated with increased utilization of recreational services, combining four surveys covering walking, boating, fishing and swimming visits, together with water quality data for all water bodies in eight River Basin Districts (RBDs) in England. We compared the percentage of visits in areas of good water quality to a set of null models accounting for population density, income, age distribution, travel distance, public access, and substitutability. We expect such association to be positive, at least for fishing (which relies on fish stocks) and swimming (with direct contact to water). We also test if these services have stronger association with water quality relative to boating and walking alongside rivers, canals or lakeshores. In only two of eight RBDs (Northumbria and Anglian) were both criteria met (positive association, strongest for fishing and swimming) when comparing to at least one of the null models. This conclusion is robust to variations in dataset size. Our study suggests that achieving the WFD water quality goals may not enhance recreational ecosystem services, and calls for further empirical research on the connection between water quality and ecosystem services

Schedule-selective biochemical modulation of 5-fluorouracil in advanced colorectal cancer – a phase II study

BACKGROUND: 5-fluorouracil remains the standard therapy for patients with advanced/metastatic colorectal cancer. Pre-clinical studies have demonstrated the biological modulation of 5-fluorouracil by methotrexate and leucovorin. This phase II study was initiated to determine the activity and toxicity of sequential methotrexate – leucovorin and 5-fluorouracil chemotherapy in patients with advanced colorectal cancer. METHODS: Ninety-seven patients with metastatic colorectal cancer were enrolled onto the study. Methotrexate – 30 mg/m(2) was administered every 6 hours for 6 doses followed by a 2 hour infusion of LV – 500 mg/m(2). Midway through the leucovorin infusion, patients received 5-fluorouracil – 600 mg/m(2). This constituted a cycle of therapy and was repeated every 2 weeks until progression. RESULTS: The median age was 64 yrs (34–84) and the Eastern Cooperative Group Oncology performance score was 0 in 37%, 1 in 55% and 2 in 8% of patients. Partial and complete responses were seen in 31% of patients with a median duration of response of 6.4 months. The overall median survival was 13.0 months. The estimated 1-year survival was 53.7%. Grade III and IV toxic effects were modest and included mucositis, nausea and vomiting. CONCLUSIONS: This phase II study supports previously reported data demonstrating the modest clinical benefit of 5-FU modulation utilizing methotrexate and leucovorin in patients with metastatic colorectal cancer. Ongoing studies evaluating 5-fluorouracil modulation with more novel agents (Irinotecan and/or oxaliplatin) are in progress and may prove encouraging