Islands of the Western Pacific

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Disease duration in autosomal dominant familial Alzheimer disease

OBJECTIVE: To use survival modeling to estimate disease duration in autosomal dominant familial Alzheimer disease (ADAD) and ascertain whether factors influencing age at onset also affect survival. METHODS: Symptomatic mutation carriers (201 presenilin 1 [PSEN1] and 55 amyloid precursor protein [APP]) from ADAD families referred to the Dementia Research Centre, between 1987 and 2019, were included. Survival was assessed with respect to age at onset, year of birth, APOE ε4 status, cognitive presentation, and sex using multilevel mixed-effects Weibull survival models. The contribution of mutation and family to variance in age at onset and duration was also assessed. RESULTS: Estimated mean survival was 11.6 (10.4–12.9) years and was similar for APP and PSEN1 mutations. Sixty-seven percent of the variance in age at onset was explained by mutation and 72% by mutation and family together. In contrast, only 6% of the variance in disease duration was explained by mutation specificity and 18% by family membership. Irrespective of gene, survival appeared longer for successive generations and in individuals with atypical presentations. Older age at onset was associated with longer duration within PSEN1 and shorter duration within APP mutation carriers. No differences in survival time were found between sexes or between mutations located before or beyond codon 200 within PSEN1. CONCLUSIONS: Survival is influenced by mutation to a much lesser extent than age at onset. Survival time has increased over time and is longer in atypical presentations. These insights may inform the interpretation of disease-modifying therapy trials in ADAD

The impact of heavy-quark loops on LHC dark matter searches

If only tree-level processes are included in the analysis, LHC monojet searches give weak constraints on the dark matter-proton scattering cross section arising from the exchange of a new heavy scalar or pseudoscalar mediator with Yukawa-like couplings to quarks. In this letter we calculate the constraints on these interactions from the CMS 5.0/fb and ATLAS 4.7/fb searches for jets with missing energy including the effects of heavy-quark loops. We find that the inclusion of such contributions leads to a dramatic increase in the predicted cross section and therefore a significant improvement of the bounds from LHC searches.Comment: 12 pages, 1 table, 3 figures, v2: extended discussion and improved relic density calculation - matches published versio

Visual short-term memory impairments in presymptomatic familial Alzheimer's disease: A longitudinal observational study

Visual short-term memory (VSTM) deficits including VSTM binding have been associated with Alzheimer's disease (AD) from preclinical to dementia stages, cross-sectionally. Yet, longitudinal investigations are lacking. The objective of this study was to evaluate VSTM function longitudinally and in relation to expected symptom onset in a cohort of familial Alzheimer's disease. Ninety-nine individuals (23 presymptomatic; 9 symptomatic and 67 controls) were included in an extension cross-sectional study and a sub-sample of 48 (23 presymptomatic carriers, 6 symptomatic and 19 controls), attending two to five visits with a median interval of 1.3 years, included in the longitudinal study. Participants completed the "What was where?" relational binding task (which measures memory for object identification, localisation and object-location binding under different conditions of memory load and delay), neuropsychology assessments and genetic testing. Compared to controls, presymptomatic carriers within 8.5 years of estimated symptom onset showed a faster rate of decline in localisation performance in long-delay conditions (4 seconds) and in traditional neuropsychology measures of verbal episodic memory. This study represents the first longitudinal VSTM investigation and shows that changes in memory resolution may be sensitive to tracking cognitive decline in preclinical AD at least as early as changes in the more traditional verbal episodic memory tasks

Earlier versus later start of antiretroviral therapy in HIV-infected adults with tuberculosis.

Tuberculosis remains an important cause of death among patients infected with the human immunodeficiency virus (HIV). Robust data are lacking with regard to the timing for the initiation of antiretroviral therapy (ART) in relation to the start of antituberculosis therapy

Energy-Efficient Multiprocessor Scheduling for Flow Time and Makespan

We consider energy-efficient scheduling on multiprocessors, where the speed of each processor can be individually scaled, and a processor consumes power $s^{\alpha}$ when running at speed $s$, for $\alpha>1$. A scheduling algorithm needs to decide at any time both processor allocations and processor speeds for a set of parallel jobs with time-varying parallelism. The objective is to minimize the sum of the total energy consumption and certain performance metric, which in this paper includes total flow time and makespan. For both objectives, we present instantaneous parallelism clairvoyant (IP-clairvoyant) algorithms that are aware of the instantaneous parallelism of the jobs at any time but not their future characteristics, such as remaining parallelism and work. For total flow time plus energy, we present an $O(1)$-competitive algorithm, which significantly improves upon the best known non-clairvoyant algorithm and is the first constant competitive result on multiprocessor speed scaling for parallel jobs. In the case of makespan plus energy, which is considered for the first time in the literature, we present an $O(\ln^{1-1/\alpha}P)$-competitive algorithm, where $P$ is the total number of processors. We show that this algorithm is asymptotically optimal by providing a matching lower bound. In addition, we also study non-clairvoyant scheduling for total flow time plus energy, and present an algorithm that achieves $O(\ln P)$-competitive for jobs with arbitrary release time and $O(\ln^{1/\alpha}P)$-competitive for jobs with identical release time. Finally, we prove an $\Omega(\ln^{1/\alpha}P)$ lower bound on the competitive ratio of any non-clairvoyant algorithm, matching the upper bound of our algorithm for jobs with identical release time

Treatment Outcomes and Cost-Effectiveness of Shifting Management of Stable ART Patients to Nurses in South Africa: An Observational Cohort

Lawrence Long and colleagues report that “down-referring” stable HIV patients from a doctor-managed, hospital-based ART clinic to a nurse-managed primary health facility provides good health outcomes and cost-effective treatment for patients

Probing the Nature of High-z Short GRB 090426 with Its Early Optical and X-ray Afterglows

GRB 090426 is a short duration burst detected by Swift ($T_{90}\sim 1.28$ s in the observer frame, and $T_{90}\sim 0.33$ s in the burst frame at $z=2.609$). Its host galaxy properties and some $\gamma$-ray related correlations are analogous to those seen in long duration GRBs, which are believed to be of a massive-star origin (so-called Type II GRBs). We present the results of its early optical observations with the 0.8-m TNT telescope at Xinglong observatory, and the 1-m LOAO telescope at Mt. Lemmon Optical Astronomy Observatory in Arizona. Our well-sampled optical afterglow lightcurve covers from $\sim 90$ seconds to $\sim 10^4$ seconds post the GRB trigger. It shows two shallow decay episodes that are likely due to energy injection, which end at $\sim 230$ seconds and $\sim 7100$ seconds, respectively. The decay slopes post the injection phases are consistent with each other ($\alpha\simeq 1.22$). The X-ray afterglow lightcurve appears to trace the optical, although the second energy injection phase was missed due to visibility constraints introduced by the {\em Swift} orbit. The X-ray spectral index is $\beta_X\sim 1.0$ without temporal evolution. Its decay slope is consistent with the prediction of the forward shock model. Both X-ray and optical emission is consistent with being in the same spectral regime above the cooling frequency ($\nu_c$). The fact that $\nu_c$ is below the optical band from the very early epoch of the observation provides a constraint on the burst environment, which is similar to that seen in classical long duration GRBs. We therefore suggest that death of a massive star is the possible progenitor of this short burst.Comment: 7 pages, 1 figures, 2 tables, revised version, MNRAS, in pres

Prolonged Survival in a Patient with Neuroendocrine Tumor of the Cecum and Diffuse Peritoneal Carcinomatosis

Peritoneal carcinomatosis is a well-known factor of poor prognosis in patients with digestive adenocarcinomas. Peritoneal dissemination may also occur in midgut well-differentiated neuroendocrine tumors, but its influence on survival is ill-defined. We report here the history of a 64-year-old woman who had a neuroendocrine tumor of the cecum with multiple synchronous metastases in the liver and diffuse peritoneal carcinomatosis. She underwent surgical resection of the primary tumor and cytoreduction of liver metastases, and received subsequently chemotherapy and somatostatin analogs. In spite of the widespread extension of the disease, she survived for 13 years and died from a carcinoid heart disease. We discuss the natural history and prognostic factors in patients with midgut well-differentiated neuroendocrine tumors, with a focus on the impact of the peritoneal carcinomatosis

Subjective cognitive complaints at age 70: associations with amyloid and mental health.

OBJECTIVE: To investigate subjective cognitive decline (SCD) in relation to β-amyloid pathology and to test for associations with anxiety, depression, objective cognition and family history of dementia in the Insight 46 study. METHODS: Cognitively unimpaired ~70-year-old participants, all born in the same week in 1946 (n=460, 49% female, 18% amyloid-positive), underwent assessments including the SCD-Questionnaire (MyCog). MyCog scores were evaluated with respect to 18F-Florbetapir-PET amyloid status (positive/negative). Associations with anxiety, depression, objective cognition (measured by the Preclinical Alzheimer Cognitive Composite, PACC) and family history of dementia were also investigated. The informant's perspective on SCD was evaluated in relation to MyCog score. RESULTS: Anxiety (mean (SD) trait anxiety score: 4.4 (3.9)) was associated with higher MyCog scores, especially in women. MyCog scores were higher in amyloid-positive compared with amyloid-negative individuals (adjusted means (95% CIs): 5.3 (4.4 to 6.1) vs 4.3 (3.9 to 4.7), p=0.044), after accounting for differences in anxiety. PACC (mean (SD) -0.05 (0.68)) and family history of dementia (prevalence: 23.9%) were not independently associated with MyCog scores. The informant's perception of SCD was generally in accordance with that of the participant. CONCLUSIONS: This cross-sectional study demonstrates that symptoms of SCD are associated with both β-amyloid pathology, and more consistently, trait anxiety in a population-based cohort of older adults, at an age when those who are destined to develop dementia are still likely to be some years away from symptoms. This highlights the necessity of considering anxiety symptoms when assessing Alzheimer's disease pathology and SCD