Canonical Distribution Law and KCl: Sm2+ Fluorescence: The C2v Paradox

A combination of critical experiments has been carried out in order to elucidate the recent conclusions of Bradbury and Wong, who attributed all the dominant KCl: Sm2+ fluorescence lines to the nearest-neighbor C2v(1,1,0)Sm2+−K+ vacancy site. In an extensive investigation into the radiationless quenching, characteristic lifetimes, excitation spectra, and Zeeman polarization of KCl: Sm2+ fluorescence lines, all the prominent lines are unequivocally attributed to a distribution of three different Sm2+ - K+ vacancy sites. In addition, 18 weak lines are shown to originate from dimeric cluster and O2− compensated sites. The paradoxical C2v interpretations of Bradbury and Wong are shown to be based on incorrect premises, inadequate experimentation, and confusion in the identity of samples with different dopant concentrations

Zeeman Anisotropy Fluorescence Spectroscopy, Characteristic Radiative Lifetimes, and Novel Site Symmetries in KCl: Sm 2+

By means of Zeeman anisotropy fluorescence (ZAF) and its field dependence (up to 55.8 kG), the authors have investigated the 4.2 K narrow-line fluorescence of KCl:Sm2+ and identified some hitherto unreported Sm2+ sites. The strong no-field line at 7693.5 Å (5D0→7F3) and a very weak no-field line at 8742.8 Å (5D0→7F5) are shown to be of C3v symmetry origin. The 24.5-kG ZAF pattern observed in the 7696-7700-Å (5D0→7F3) region has been identified to originate from a type-II Cs site. The 26.5-kG ZAF patterns of the C3v no-field line at 7693.5 Å and the type-I Cs no-field line at 7694.5 Å overlap in the 7693-7695.3-Å region, and are elucidated through the field dependence of their Zeeman components. Characteristic radiative lifetimes of the 5D0 level in several Sm2+ symmetry types have been determined from dominant transitions to the 7FJ (J\u3c~4) levels. There are two distinct C4v sites: one with a lifetime of 9.5 msec, and the other 11.2 msec. C2v and type-I Cs sites have lifetimes of 10.5 and 10.8 msec, respectively, which are indistinguishable within the experimental error. The role of O2− compensation of Sm2+ in addition to K+ vacancy compensation in KCl is discussed in terms of these findings

The burden of proof: the current state of atrial fibrillation prevention and treatment trials

Atrial fibrillation (AF) is an age-related arrhythmia of enormous socioeconomic significance. In recent years, our understanding of the basic mechanisms that initiate and perpetuate AF has evolved rapidly, catheter ablation of AF has progressed from concept to reality, and recent studies suggest lifestyle modification may help prevent AF recurrence. Emerging developments in genetics, imaging, and informatics also present new opportunities for personalized care. However, considerable challenges remain. These include a paucity of studies examining AF prevention, modest efficacy of existing antiarrhythmic therapies, diverse ablation technologies and practice, and limited evidence to guide management of high-risk patients with multiple comorbidities. Studies examining the long-term effects of AF catheter ablation on morbidity and mortality outcomes are not yet completed. In many ways, further progress in the field is heavily contingent on the feasibility, capacity, and efficiency of clinical trials to incorporate the rapidly evolving knowledge base and to provide substantive evidence for novel AF therapeutic strategies. This review outlines the current state of AF prevention and treatment trials, including the foreseeable challenges, as discussed by a unique forum of clinical trialists, scientists, and regulatory representatives in a session endorsed by the Heart Rhythm Society at the 12th Global CardioVascular Clinical Trialists Forum in Washington, DC, December 3–5, 2015

Dynamics of forest cover conversion in and around Bwindi impenetrable forest, Southwestern Uganda

Forest cover has been converted to agricultural land use in and around the protected areas of Uganda. The objectives of this study were; to examine the dynamics of forest cover change in and around Bwindi impenetrable forest between 1973 and 2010 and to identify the drivers of forest cover change. The trend in forest cover change was assessed by analyzing a series of orthorectified landsat imageries of 1973, 1987 and 2001 using unsupervised and supervised classification. Land use/cover map for 2010 was reconstructed by analyzing 2001 image, validated and/or reconstructed by ground truthing, use of secondary data and key informant interviews. A series of focused group discussions and key informant interviews were also used to identify drivers of land use/cover change. Policies and institutional arrangements that could have affected forest cover change for the studied time period were also identified. Results showed that protected forest and woodlot in unprotected area had declined by 7.8% and 70.7% respectively as small scale farming and tea plantations had increased by 13.9% and 78.3% respectively between 1973 and 2010. The conversions were attributed to land use pressure due to population growth, change in socio-economic conditions and institutional arrangements. The severe loss of woodlot outside the protected area not only poses a potential threat to the protected forest but also calls for intervention measures if efforts to mitigate climate change impacts are to be realized

Phase I dose-escalation trial of the oral AKT inhibitor uprosertib in combination with the oral MEK1/MEK2 inhibitor trametinib in patients with solid tumors.

PurposeThis study aimed to determine the safety, tolerability, and recommended phase II doses of trametinib plus uprosertib (GSK2141795) in patients with solid tumors likely to be sensitive to MEK and/or AKT inhibition.MethodsThis was a phase I, open-label, dose-escalation, and dose-expansion study in patients with triple-negative breast cancer or BRAF-wild type advanced melanoma. The primary outcome of the expansion study was investigator-assessed response. Among 126 enrolled patients, 63 received continuous oral daily dosing of trametinib and uprosertib, 29 received various alternative dosing schedules, and 34 were enrolled into expansion cohorts. Doses tested in the expansion cohort were trametinib 1.5 mg once daily (QD) + uprosertib 50 mg QD.ResultsAdverse events (AEs) were consistent with those reported in monotherapy studies but occurred at lower doses and with greater severity. Diarrhea was the most common dose-limiting toxicity; diarrhea and rash were particularly difficult to tolerate. Overall, 59% and 6% of patients reported AEs with a maximum severity of grade 3 and 4, respectively. Poor tolerability prevented adequate delivery of uprosertib with trametinib at a concentration predicted to have clinical activity. The study was terminated early based on futility in the continuous-dosing expansion cohorts and a lack of pharmacological or therapeutic advantage with intermittent dosing. The objective response rate was < 5% (1 complete response, 5 partial responses).ConclusionsContinuous and intermittent dosing of trametinib in combination with uprosertib was not tolerated, and minimal clinical activity was observed in all schedules tested

Evidence of Limited Recruitment of Pallid Sturgeon in the Lower Missouri River

Pallid Sturgeon Scaphirhynchus albus are endemic to the Missouri and Mississippi river basins and are rare throughout their range. The species was listed as federally endangered with little to no evidence of natural recruitment. Since population augmentation was initiated as a recovery objective in the early 1990s, thousands of hatchery-origin Pallid Sturgeon have been stocked in the lower Missouri River (Gavins Point Dam [river kilometer 1,305.1] to the confluence of the Mississippi River [river kilometer 0.0]). Efforts to discriminate natural reproduction and recruitment of wild-origin Pallid Sturgeon from hatchery-origin fish has been hampered by tag loss in hatchery-origin sturgeon, inconsistent documentation of hatchery parental crosses, and the failure to collect tissue samples for genotyping all broodstock. However, the recent reconstruction of missing parental genotypes from known hatchery-origin progeny and from cryopreserved milt made it possible to examine Pallid Sturgeon recruitment. Therefore, our objectives were to 1) determine the likelihood that unmarked Pallid Sturgeon captured from the lower Missouri River were the result of natural recruitment and 2) examine the length distribution of wild- and hatchery-origin fish to determine if a difference exists by origin and examine the life-stage distribution. Genetic analysis showed that from 2003 to 2015, 358 ‘‘presumptive wild-origin’’ Pallid Sturgeon were captured in the lower Missouri River and the comparison between the length distributions of wild- and hatchery-origin fish did not provide any additional clarification into potential wildorigin fish. Low recruitment may be due to a small breeding population, high mortality of early life stages, hybridization with Shovelnose Sturgeon Scaphirhynchus platorynchus, or transport of drifting free embryos or larvae into inhospitable habitats. Determining what factors are limiting recruitment is the important next step for the recovery of Pallid Sturgeon in the lower Missouri River

Dynamics of forest cover conversion in and around Bwindi impenetrable forest, Southwestern Uganda

Forest cover has been converted to agricultural land use in and around the protected areas of Uganda. The objectives of this study were; to examine the dynamics of forest cover change in and around Bwindi impenetrable forest between 1973 and 2010 and to identify the drivers of forest cover change. The trend in forest cover change was assessed by analyzing a series of orthorectified landsat imageries of 1973, 1987 and 2001 using unsupervised and supervised classification. Land use/cover map for 2010 was reconstructed by analyzing 2001 image, validated and/or reconstructed by ground truthing, use of secondary data and key informant interviews. A series of focused group discussions and key informant interviews were also used to identify drivers of land use/cover change. Policies and institutional arrangements that could have affected forest cover change for the studied time period were also identified. Results showed that protected forest and woodlot in unprotected area had declined by 7.8% and 70.7% respectively as small scale farming and tea plantations had increased by 13.9% and 78.3% respectively between 1973 and 2010. The conversions were attributed to land use pressure due to population growth, change in socio-economic conditions and institutional arrangements. The severe loss of woodlot outside the protected area not only poses a potential threat to the protected forest but also calls for intervention measures if efforts to mitigate climate change impacts are to be realized

Brief Report: Safety and Antitumor Activity of Alectinib Plus Atezolizumab From a Phase 1b Study in Advanced ALK-Positive NSCLC

INTRODUCTION: Alectinib is a preferred first-line treatment option for advanced ALK-positive NSCLC. Combination regimens of alectinib with immune checkpoint inhibitors are being evaluated for synergistic effects. METHODS: Adults with treatment-naive, stage IIIB/IV, or recurrent ALK-positive NSCLC were enrolled into a two-stage phase 1b study. Patients received alectinib 600 mg (twice daily during cycle 1 and throughout each 21-d cycle thereafter) plus atezolizumab 1200 mg (d8 of cycle 1 and then d1 of each 21-d cycle). Primary objectives were to evaluate safety and tolerability of alectinib plus atezolizumab. Secondary objectives included assessments of antitumor activity. RESULTS: In total, 21 patients received more than or equal to 1 dose of alectinib or atezolizumab. As no dose-limiting toxicities were observed in stage 1 (n = 7), the starting dose and schedule were continued into stage 2 (n = 14). Median duration of follow-up was 29 months (range: 1-39). Grade 3 treatment-related adverse events occurred in 57% of the patients, most often rash (19%). No grade 4 or 5 treatment-related adverse events were reported. Confirmed objective response rate was 86% (18 of 21; 95% confidence interval [CI]: 64-97). Median progression-free survival was not estimable (NE) (95% CI: 13 mo-NE), neither was median overall survival (95% CI: 33 mo-NE). CONCLUSIONS: The combination of alectinib and atezolizumab is feasible, but increased toxicity was found compared with the individual agents. With small sample sizes and relatively short follow-up, definitive conclusions regarding antitumor activity cannot be made

Population structure, connectivity, and demographic history of an apex marine predator, the bull shark <i>Carcharhinus leucas</i>

Knowledge of population structure, connectivity, and effective population size remains limited for many marine apex predators, including the bull shark Carcharhinus leucas. This large‐bodied coastal shark is distributed worldwide in warm temperate and tropical waters, and uses estuaries and rivers as nurseries. As an apex predator, the bull shark likely plays a vital ecological role within marine food webs, but is at risk due to inshore habitat degradation and various fishing pressures. We investigated the bull shark\u27s global population structure and demographic history by analyzing the genetic diversity of 370 individuals from 11 different locations using 25 microsatellite loci and three mitochondrial genes (CR, nd4, and cytb). Both types of markers revealed clustering between sharks from the Western Atlantic and those from the Western Pacific and the Western Indian Ocean, with no contemporary gene flow. Microsatellite data suggested low differentiation between the Western Indian Ocean and the Western Pacific, but substantial differentiation was found using mitochondrial DNA. Integrating information from both types of markers and using Bayesian computation with a random forest procedure (ABC‐RF), this discordance was found to be due to a complete lack of contemporary gene flow. High genetic connectivity was found both within the Western Indian Ocean and within the Western Pacific. In conclusion, these results suggest important structuring of bull shark populations globally with important gene flow occurring along coastlines, highlighting the need for management and conservation plans on regional scales rather than oceanic basin scale