Association of β-Amyloid Burden With Sleep Dysfunction and Cognitive Impairment in Elderly Individuals With Cognitive Disorders.

Importance: Evidence shows that sleep dysfunction and β-amyloid (Aβ) deposition work synergistically to impair brain function in individuals with normal cognition, increasing the risk of developing dementia later in life. However, whether Aβ continues to play an integral role in sleep dysfunction after the onset of cognitive decline in individuals with dementia is unclear. Objective: To determine whether Aβ deposition in the brain is associated with subjective measures of sleep quality and cognition in elderly individuals with cognitive disorders. Design, Setting, and Participants: A nested survey study was conducted at the Cognitive Disorders and Comprehensive Alzheimer Disease Center of Thomas Jefferson University Hospital in Philadelphia, Pennsylvania. Participants included patients aged 65 years and older with cognitive disorders verified by neuropsychological testing. Eligible participants were identified from a referral center-based sample of patients who underwent fluorine 18-labeled florbetaben positron emission tomography imaging at Thomas Jefferson University Hospital as part of the multicenter Imaging Dementia-Evidence for Amyloid Scanning study. Data collection and analysis occurred between November 2018 and March 2019. Main Outcomes and Measures: Sleep quality was measured via responses to sleep questionnaires, Aβ deposition was measured via fluorine 18-labeled florbetaben positron emission tomography, and cognition was measured via Mini-Mental State Examination (MMSE) performance. Results: Of the 67 eligible participants, 52 (77.6%) gave informed consent to participate in the study. Of the 52 enrolled participants (mean [SD] age, 76.6 [7.4] years), 27 (51.9%) were women. Daytime sleepiness was associated with Aβ deposition in the brainstem (B = 0.0063; 95% CI, 0.001 to 0.012; P = .02), but not MMSE performance (B = -0.01; 95% CI, -0.39 to 0.37; P = .96). The number of nocturnal awakenings was associated with Aβ deposition in the precuneus (B = 0.11; 95% CI, 0.06 to 0.17; P \u3c .001) and poor MMSE performance (B = -2.13; 95% CI, -3.13 to -1.13; P \u3c .001). Mediation analysis demonstrated an indirect association between Aβ deposition and poor MMSE performance that relied on nocturnal awakenings as an intermediary (B = -3.99; 95% CI, -7.88 to -0.83; P = .01). Conclusions and Relevance: Nighttime sleep disruption may mediate the association between Aβ and cognitive impairment, suggesting that there is an underlying sleep-dependent mechanism that links Aβ burden in the brain to cognitive decline. Further elucidation of this mechanism may improve understanding of disease processes associated with Aβ accumulation

An unmanned aerial vehicle sampling platform for atmospheric water vapor isotopes in polar environments

Above polar ice sheets, atmospheric water vapor exchange occurs across the planetary boundary layer (PBL) and is an important mechanism in a number of processes that affect the surface mass balance of the ice sheets. Yet, this exchange is not well understood and has substantial implications for modeling and remote sensing of the polar hydrologic cycle. Efforts to characterize the exchange face substantial logistical challenges including the remoteness of ice sheet field camps, extreme weather conditions, low humidity and temperature that limit the effectiveness of instruments, and dangers associated with flying manned aircraft at low altitudes. Here, we present an unmanned aerial vehicle (UAV) sampling platform for operation in extreme polar environments that is capable of sampling atmospheric water vapor for subsequent measurement of water isotopes. This system was deployed to the East Greenland Ice-core Project (EastGRIP) camp in northeast Greenland during summer 2019. Four sampling flight missions were completed. With a suite of atmospheric measurements aboard the UAV (temperature, humidity, pressure, GPS) we determine the height of the PBL using online algorithms, allowing for strategic decision-making by the pilot to sample water isotopes above and below the PBL. Water isotope data were measured by a Picarro L2130-i instrument using flasks of atmospheric air collected within the nose cone of the UAV. The internal repeatability for δD and δ18O was 2.8 ‰ and 0.45 ‰, respectively, which we also compared to independent EastGRIP tower-isotope data. Based on these results, we demonstrate the efficacy of this new UAV-isotope platform and present improvements to be utilized in future polar field campaigns. The system is also designed to be readily adaptable to other fields of study, such as measurement of carbon cycle gases or remote sensing of ground conditions.publishedVersio

Factors associated with survival in small cell lung cancer: an analysis of real-world national audit, chemotherapy and radiotherapy data

Background: The mainstay of treatment for small cell lung cancer (SCLC) involves platinum doublet chemotherapy but the optimal duration, 4 vs. 6 cycles, is not known. Concurrent thoracic radiotherapy followed by prophylactic cranial irradiation (PCI) is recommended for fit individuals with limited stage. However, outside of clinical trials, the efficacy of sequential thoracic radiotherapy and PCI for extensive stage is uncertain.Methods: This retrospective, observational, cohort study used English national lung cancer data to determine the factors associated with survival for all people diagnosed with SCLC. More precisely, for individuals who received chemotherapy, we examined survival by the chemotherapy duration, thoracic radiotherapy dose and the use of PCI.Results: In total 6,438 people were diagnosed with SCLC. We identified that male sex (OR 0.7; 95% CI: 0.62–0.80), increasing age (P=0.01) greater comorbidity (P≤0.01), extensive stage (OR 0.21; 95% CI: 0.19–0.25) and worse performance status (PS2 vs. PS0 adjusted OR 0.38 95% CI: 0.31–0.48) were associated with reduced 1-year survival. Receipt of chemotherapy augmented survival. We analysed data for 1,761 people who had received chemotherapy. Thoracic radiotherapy (≥30 Gy for extensive stage and ≥40 Gy for limited stage) and PCI were independently associated with better survival (P≤0.01 for each), but 6 cycles of chemotherapy instead of 4 was not (limited stage adjusted OR 0.97; 95% CI: 0.48–1.97) extensive stage adjusted OR 1.34; 95% CI: 0.81–2.21).Conclusions: Extending chemotherapy beyond 4 cycles to 6 does not augment survival. Appropriately prescribed thoracic radiotherapy and PCI can prolong survival in both limited and extensive stage SCLC

The Antiviral Efficacy of HIV-Specific CD8+ T-Cells to a Conserved Epitope Is Heavily Dependent on the Infecting HIV-1 Isolate

A major challenge to developing a successful HIV vaccine is the vast diversity of viral sequences, yet it is generally assumed that an epitope conserved between different strains will be recognised by responding T-cells. We examined whether an invariant HLA-B8 restricted Nef90–97 epitope FL8 shared between five high titre viruses and eight recombinant vaccinia viruses expressing Nef from different viral isolates (clades A–H) could activate antiviral activity in FL8-specific cytotoxic T-lymphocytes (CTL). Surprisingly, despite epitope conservation, we found that CTL antiviral efficacy is dependent on the infecting viral isolate. Only 23% of Nef proteins, expressed by HIV-1 isolates or as recombinant vaccinia-Nef, were optimally recognised by CTL. Recognition of the HIV-1 isolates by CTL was independent of clade-grouping but correlated with virus-specific polymorphisms in the epitope flanking region, which altered immunoproteasomal cleavage resulting in enhanced or impaired epitope generation. The finding that the majority of virus isolates failed to present this conserved epitope highlights the importance of viral variance in CTL epitope flanking regions on the efficiency of antigen processing, which has been considerably underestimated previously. This has important implications for future vaccine design strategies since efficient presentation of conserved viral epitopes is necessary to promote enhanced anti-viral immune responses

Spongivory in the Wakatobi Marine National Park, Southeast Sulawesi, Indonesia

Sponges are functionally important coral reef fauna and there is strong evidence from the Caribbean that predation has important impacts on sponge-Assemblage dynamics; whether the same is true for Indo-Pacific sponges remains unknown. As a first step toward understanding the potential effects of spongivores on sponge diversity and abundance, we identified sponge predators at nine sites in Wakatobi Marine National Park, Indonesia, and conducted a short-Term caging experiment to examine the effects of excluding predators on noncryptic reef sponges at this location. Nudibranchs were the most abundant invertebrate spongivores, although their low densities are likely to limit their influence on sponges. Fish were the most abundant vertebrate spongivores with 16 species from six families observed feeding on sponges. Based on their abundance and our feeding observations, the fish with the greatest potential to influence sponge assemblages in Wakatobi Marine National Park were Zanclus cornutus, Chaetodon kleinii, Pygoplites diacanthus, and Pomacanthus sexstriatus. We did not detect an effect of excluding spongivores on noncryptic reef sponge abundance in our caging experiment, which may be due to these species having evolved chemical defenses against predators. Important areas for further research include the chemical ecology of Indo-Pacific sponges and whether spongivory currently restricts some species to cryptic or nonreef habitats

Canine Morphology: Hunting for Genes and Tracking Mutations

In this essay, Abigail Shearin and Elaine Ostrander discuss the proposed genomic mechanisms for the extraordinary level of phenotypic variation observed in the domestic dog and the evidence detailing the variants responsible for the many shapes, sizes, textures, and colors of man's best friend

Державне регулювання системи факторів оцінки та мінімізації ризиків легалізації коштів, одержаних злочинним шляхом в процесі фінансового моніторингу комерційних банків України

Основною ціллю данної статті є формулювання важливості впливу чітко визначених факторів, які впливають на процеси фінансового моніторингу в комерційних банків України. Виходячи з поставлених цілей, завданнями даної статті є розроблення моделі оцінки ризиків банківської установи щодо протидії легалізації коштів одержаних злочинним шляхом в системі внутрішньобанківського фінансового моніторингу, та використання в подальшому запропонованих стратегій управління наслідками даних ризиків

Lassa Fever in Post-Conflict Sierra Leone

Background: Lassa fever (LF), an often-fatal hemorrhagic disease caused by Lassa virus (LASV), is a major public health threat in West Africa. When the violent civil conflict in Sierra Leone (1991 to 2002) ended, an international consortium assisted in restoration of the LF program at Kenema Government Hospital (KGH) in an area with the world's highest incidence of the disease. Methodology/Principal Findings Clinical and laboratory records of patients presenting to the KGH Lassa Ward in the post-conflict period were organized electronically. Recombinant antigen-based LF immunoassays were used to assess LASV antigenemia and LASV-specific antibodies in patients who met criteria for suspected LF. KGH has been reestablished as a center for LF treatment and research, with over 500 suspected cases now presenting yearly. Higher case fatality rates (CFRs) in LF patients were observed compared to studies conducted prior to the civil conflict. Different criteria for defining LF stages and differences in sensitivity of assays likely account for these differences. The highest incidence of LF in Sierra Leone was observed during the dry season. LF cases were observed in ten of Sierra Leone's thirteen districts, with numerous cases from outside the traditional endemic zone. Deaths in patients presenting with LASV antigenemia were skewed towards individuals less than 29 years of age. Women self-reporting as pregnant were significantly overrepresented among LASV antigenemic patients. The CFR of ribavirin-treated patients presenting early in acute infection was lower than in untreated subjects. Conclusions/Significance: Lassa fever remains a major public health threat in Sierra Leone. Outreach activities should expand because LF may be more widespread in Sierra Leone than previously recognized. Enhanced case finding to ensure rapid diagnosis and treatment is imperative to reduce mortality. Even with ribavirin treatment, there was a high rate of fatalities underscoring the need to develop more effective and/or supplemental treatments for LF