Benefit Plan Cybersecurity Considerations: A Recordkeeper and Plan Perspective

The U.S. has no comprehensive national law governing cybersecurity and no uniform framework for measuring the effectiveness of protections, though retirement plan record keepers maintain the personally identifiable information on millions of workers, collecting names, birth dates, social security numbers, and beneficiaries. Plan sponsors frequently engage consultants and attorneys to help them secure sensitive data, but more work is necessary to engage a larger discussion around this issue. The SPARK Institute has outlined a flexible approach for an independent third-party reporting of cyber security capabilities with several key control objectives

Cumulative Network Meta-Analysis and Clinical Practice Guidelines: A Case Study on First-Line Medical Therapies for Primary Open-Angle Glaucoma

Background: Clinical practice guidelines are statements of recommendations for patient care. Studies have shown that guideline recommendations do not always depend on evidence from clinical trials or systematic reviews. It is unknown whether no high quality evidence exists, evidence exists but authors were unaware of it, or advanced statistical methods were not available to them to address their questions. Our objective was to compare the guideline recommendations for first-line medical therapy for primary open-angle glaucoma (POAG) from each major update of the American Academy of Ophthalmology’s (AAO) Preferred Practice Patterns (PPPs) with the actual evidence base available at the time. Methods: We identified and extracted recommendations relevant to first-line medical therapy for POAG from each version of the AAO PPP. We searched MEDLINE, EMBASE, and CENTRAL for randomized controlled trials published up to March 2014. We analyzed intraocular pressure (IOP) outcome data as available at the time of each major guideline update. We used network meta-analysis to determine which of all drugs “works best.” Results: We identified 9 versions of AAO’s guideline for POAG published between 1989 and 2010. Based on similarity in treatment recommendations or discussion, we grouped these guidelines into 5 sets: 1989-1992, 1996, 2000-2003; 2005-2006, and 2010. The 2010 guideline recommended prostaglandins as initial treatment, but previous sets presented treatment options without recommending one drug (or class) over another. Based on a series of network meta-analyses of trials published up to around the time of the latest guideline in each set, all drugs are more effective than placebo or no treatment at each time point, but effect size appears to decrease over time. Network meta-analysis indicated that the most effective drug and class (at time point analyzed) were: levobunolol and beta blockers (1991), levobunolol and alpha agonists (1995), travoprost and prostaglandins (2002), bimatoprost and prostaglandins (2004 and 2009). Conclusions: Network meta-analysis improves our understanding of the comparative effectiveness of multiple interventions. Had network meta-analysis been available, the AAO POAG PPP could have recommended prostaglandins (current first-line treatment) seven years before it actually did. Guideline developers should consider using results from network meta-analyses in forming future recommendations

Combinatorial Proofs of Fermat\u27s, Lucas\u27s, and Wilson\u27s Theorems

No abstract provided in this article

Freezing of Spinodal Decompostion by Irreversible Chemical Growth Reaction

We present a description of the freezing of spinodal decomposition in systems, which contain simultaneous irreversible chemical reactions, in the hydrodynamic limit approximation. From own results we conclude, that the chemical reaction leads to an onset of spinodal decomposition also in the case of an initial system which is completely miscible and can lead to an extreme retardation of the dynamics of the spinodal decomposition, with the probability of a general freezing of this process, which can be experimetally observed in simultaneous IPN formation.Comment: 10 page

Treatment for HIV-associated cryptococcal meningitis.

BACKGROUND: Cryptococcal meningitis is a severe fungal infection that occurs primarily in the setting of advanced immunodeficiency and remains a major cause of HIV-related deaths worldwide. The best induction therapy to reduce mortality from HIV-associated cryptococcal meningitis is unclear, particularly in resource-limited settings where management of drug-related toxicities associated with more potent antifungal drugs is a challenge. OBJECTIVES: To evaluate the best induction therapy to reduce mortality from HIV-associated cryptococcal meningitis; to compare side effect profiles of different therapies. SEARCH METHODS: We searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL, MEDLINE (PubMed), Embase (Ovid), LILACS (BIREME), African Index Medicus, and Index Medicus for the South-East Asia Region (IMSEAR) from 1 January 1980 to 9 July 2018. We also searched the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), ClinicalTrials.gov, and the ISRCTN registry; and abstracts of select conferences published between 1 July 2014 and 9 July 2018. SELECTION CRITERIA: We included randomized controlled trials that compared antifungal induction therapies used for the first episode of HIV-associated cryptococcal meningitis. Comparisons could include different individual or combination therapies, or the same antifungal therapies with differing durations of induction (less than two weeks or two or more weeks, the latter being the current standard of care). We included data regardless of age, geographical region, or drug dosage. We specified no language restriction. DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles and abstracts identified by the search strategy. We obtained the full texts of potentially eligible studies to assess eligibility and extracted data using standardized forms. The main outcomes included mortality at 2 weeks, 10 weeks, and 6 months; mean rate of cerebrospinal fluid fungal clearance in the first two weeks of treatment; and Division of AIDS (DAIDS) grade three or four laboratory events. Using random-effects models we determined pooled risk ratio (RR) and 95% confidence interval (CI) for dichotomous outcomes and mean differences (MD) and 95% CI for continuous outcomes. For the direct comparison of 10-week mortality, we assessed the certainty of the evidence using the GRADE approach. We performed a network meta-analysis using multivariate meta-regression. We modelled treatment differences (RR and 95% CI) and determined treatment rankings for two-week and 10-week mortality outcomes using surface under the cumulative ranking curve (SUCRA). We assessed transitivity by comparing distribution of effect modifiers between studies, local inconsistency through a node-splitting approach, and global inconsistency using design-by-treatment interaction modelling. For the network meta-analysis, we applied a modified GRADE approach for assessing the certainty of the evidence for 10-week mortality. MAIN RESULTS: We included 13 eligible studies that enrolled 2426 participants and compared 21 interventions. All studies were carried out in adults, and all but two studies were conducted in resource-limited settings, including 11 of 12 studies with 10-week mortality data.In the direct pairwise comparisons evaluating 10-week mortality, one study from four sub-Saharan African countries contributed data to several key comparisons. At 10 weeks these data showed that those on the regimen of one-week amphotericin B deoxycholate (AmBd) and flucytosine (5FC) followed by fluconazole (FLU) on days 8 to 14 had lower mortality when compared to (i) two weeks of AmBd and 5FC (RR 0.62, 95% CI 0.42 to 0.93; 228 participants, 1 study), (ii) two weeks of AmBd and FLU (RR 0.58, 95% CI 0.39 to 0.86; 227 participants, 1 study), (iii) one week of AmBd with two weeks of FLU (RR 0.49, 95% CI 0.34 to 0.72; 224 participants, 1 study), and (iv) two weeks of 5FC and FLU (RR 0.68, 95% CI 0.47 to 0.99; 338 participants, 1 study). The evidence for each of these comparisons was of moderate certainty. For other outcomes, this shortened one-week AmBd and 5FC regimen had similar fungal clearance (MD 0.05 log10 CFU/mL/day, 95% CI -0.02 to 0.12; 186 participants, 1 study) as well as lower risk of grade three or four anaemia (RR 0.31, 95% CI 0.16 to 0.60; 228 participants, 1 study) compared to the two-week regimen of AmBd and 5FC.For 10-week mortality, the comparison of two weeks of 5FC and FLU with two weeks of AmBd and 5FC (RR 0.92, 95% CI 0.69 to 1.23; 340 participants, 1 study) or two weeks of AmBd and FLU (RR 0.85, 95% CI 0.64 to 1.13; 339 participants, 1 study) did not show a difference in mortality, with moderate-certainty evidence for both comparisons.When two weeks of combination AmBd and 5FC was compared with AmBd alone, pooled data showed lower mortality at 10 weeks (RR 0.66, 95% CI 0.46 to 0.95; 231 participants, 2 studies, moderate-certainty evidence).When two weeks of AmBd and FLU was compared to AmBd alone, there was no difference in 10-week mortality in pooled data (RR 0.94, 95% CI 0.55 to 1.62; 371 participants, 3 studies, low-certainty evidence).One week of AmBd and 5FC followed by FLU on days 8 to 14 was the best induction therapy regimen after comparison with 11 other regimens for 10-week mortality in the network meta-analysis, with an overall SUCRA ranking of 88%. AUTHORS' CONCLUSIONS: In resource-limited settings, one-week AmBd- and 5FC-based therapy is probably superior to other regimens for treatment of HIV-associated cryptococcal meningitis. An all-oral regimen of two weeks 5FC and FLU may be an alternative in settings where AmBd is unavailable or intravenous therapy cannot be safely administered. We found no mortality benefit of combination two weeks AmBd and FLU compared to AmBd alone. Given the absence of data from studies in children, and limited data from high-income countries, our findings provide limited guidance for treatment in these patients and settings

Biodiversity on the Rocks : Macrofauna Inhabiting Authigenic Carbonate at Costa Rica Methane Seeps

Carbonate communities:The activity of anaerobic methane oxidizing microbes facilitates precipitation of vast quantities of authigenic carbonate at methane seeps. Here we demonstrate the significant role of carbonate rocks in promoting diversity by providing unique habitat and food resources for macrofaunal assemblages at seeps on the Costa Rica margin (400–1850 m). The attendant fauna is surprisingly similar to that in rocky intertidal shores, with numerous grazing gastropods (limpets and snails) as dominant taxa. However, the community feeds upon seep-associated microbes. Macrofaunal density, composition, and diversity on carbonates vary as a function of seepage activity, biogenic habitat and location. The macrofaunal community of carbonates at non-seeping (inactive) sites is strongly related to the hydrography (depth, temperature, O2) of overlying water, whereas the fauna at sites of active seepage is not. Densities are highest on active rocks from tubeworm bushes and mussel beds, particularly at the Mound 12 location (1000 m). Species diversity is higher on rocks exposed to active seepage, with multiple species of gastropods and polychaetes dominant, while crustaceans, cnidarians, and ophiuroids were better represented on rocks at inactive sites. Macro-infauna (larger than 0.3 mm) from tube cores taken in nearby seep sediments at comparable depths exhibited densities similar to those on carbonate rocks, but had lower diversity and different taxonomic composition. Seep sediments had higher densities of ampharetid, dorvilleid, hesionid, cirratulid and lacydoniid polychaetes, whereas carbonates had more gastropods, as well as syllid, chrysopetalid and polynoid polychaetes. Stable isotope signatures and metrics: The stable isotope signatures of carbonates were heterogeneous, as were the food sources and nutrition used by the animals. Carbonate δ13Cinorg values (mean = -26.98‰) ranged from -53.3‰to +10.0‰, and were significantly heavier than carbonate δ13Corg (mean = -33.83‰), which ranged from -74.4‰to -20.6‰. Invertebrates on carbonates had average δ13C (per rock) = -31.0‰ (range -18.5‰to -46.5‰) and δ15N = 5.7‰(range -4.5‰to +13.4‰). Average δ13C values did not differ between active and inactive sites; carbonate fauna from both settings depend on chemosynthesis-based nutrition. Community metrics reflecting trophic diversity (SEAc, total Hull Area, ranges of δ13C and δ15N) and species packing (mean distance to centroid, nearest neighbor distance) also did not vary as a function of seepage activity or site. However, distinct isotopic signatures were observed among related, co-occurring species of gastropods and polychaetes, reflecting intense microbial resource partitioning. Overall, the substrate and nutritional heterogeneity introduced by authigenic seep carbonates act to promote diverse, uniquely adapted assemblages, even after seepage ceases. The macrofauna in these ecosystems remain largely overlooked in most surveys, but are major contributors to biodiversity of chemosynthetic ecosystems and the deep sea in general

Climatic and geographic predictors of life history variation in Eastern Massasauga (Sistrurus catenatus): A range-wide synthesis

Elucidating how life history traits vary geographically is important to understanding variation in population dynamics. Because many aspects of ectotherm life history are climate-dependent, geographic variation in climate is expected to have a large impact on population dynamics through effects on annual survival, body size, growth rate, age at first reproduction, size-fecundity relationship, and reproductive frequency. The Eastern Massasauga (Sistrurus catenatus) is a small, imperiled North American rattlesnake with a distribution centered on the Great Lakes region, where lake effects strongly influence local conditions. To address Eastern Massasauga life history data gaps, we compiled data from 47 study sites representing 38 counties across the range. We used multimodel inference and general linear models with geographic coordinates and annual climate normals as explanatory variables to clarify patterns of variation in life history traits. We found strong evidence for geographic variation in six of nine life history variables. Adult female snout-vent length and neonate mass increased with increasing mean annual precipitation. Litter size decreased with increasing mean temperature, and the size-fecundity relationship and growth prior to first hibernation both increased with increasing latitude. The proportion of gravid females also increased with increasing latitude, but this relationship may be the result of geographically varying detection bias. Our results provide insights into ectotherm life history variation and fill critical data gaps, which will inform Eastern Massasauga conservation efforts by improving biological realism for models of population viability and climate change