Triangulating evidence from observational and Mendelian randomization studies of ketone bodies for cognitive performance

BACKGROUND: Ketone bodies (KBs) are an alternative energy supply for brain functions when glucose is limited. The most abundant ketone metabolite, 3-β-hydroxybutyrate (BOHBUT), has been suggested to prevent or delay cognitive impairment, but the evidence remains unclear. We triangulated observational and Mendelian randomization (MR) studies to investigate the association and causation between KBs and cognitive function. METHODS: In observational analyses of 5506 participants aged ≥ 45 years from the Whitehall II study, we used multiple linear regression to investigate the associations between categorized KBs and cognitive function scores. Two-sample MR was carried out using summary statistics from an in-house KBs meta-analysis between the University College London-London School of Hygiene and Tropical Medicine-Edinburgh-Bristol (UCLEB) Consortium and Kettunen et al. (N = 45,031), and publicly available summary statistics of cognitive performance and Alzheimer's disease (AD) from the Social Science Genetic Association Consortium (N = 257,841), and the International Genomics of Alzheimer's Project (N = 54,162), respectively. Both strong (P < 5 × 10-8) and suggestive (P < 1 × 10-5) sets of instrumental variables for BOHBUT were applied. Finally, we performed cis-MR on OXCT1, a well-known gene for KB catabolism. RESULTS: BOHBUT was positively associated with general cognitive function (β = 0.26, P = 9.74 × 10-3). In MR analyses, we observed a protective effect of BOHBUT on cognitive performance (inverse variance weighted: βIVW = 7.89 × 10-2, PIVW = 1.03 × 10-2; weighted median: βW-Median = 8.65 × 10-2, PW-Median = 9.60 × 10-3) and a protective effect on AD (βIVW =  - 0.31, odds ratio: OR = 0.74, PIVW = 3.06 × 10-2). Cis-MR showed little evidence of therapeutic modulation of OXCT1 on cognitive impairment. CONCLUSIONS: Triangulation of evidence suggests that BOHBUT has a beneficial effect on cognitive performance. Our findings raise the hypothesis that increased BOHBUT may improve general cognitive functions, delaying cognitive impairment and reducing the risk of AD

Entanglement-based quantum communication secured by nonlocal dispersion cancellation

Quantum key distribution (QKD) enables participants to exchange secret information over long distances with unconditional security. However, the performance of today's QKD systems is subject to hardware limitations, such as those of available nonclassical-light sources and single-photon detectors. By encoding photons in high-dimensional states, the rate of generating secure information under these technical constraints can be maximized. Here, we demonstrate a complete time-energy entanglement-based QKD system with proven security against the broad class of arbitrary collective attacks. The security of the system is based on nonlocal dispersion cancellation between two time-energy entangled photons. This resource-efficient QKD system is implemented at telecommunications wavelength, is suitable for optical fiber and free-space links, and is compatible with wavelength-division multiplexing.United States. Army Research Office (Defense Advanced Research Projects Agency. Information in a Photon (InPho) Program (Grant W911NF-10-1-0416))National Science Foundation (U.S.). Integrative Graduate Education and Research Traineeship (Grant DGE-1069420

Photon-efficient quantum key distribution using time–energy entanglement with high-dimensional encoding

Conventional quantum key distribution (QKD) typically uses binary encoding based on photon polarization or time-bin degrees of freedom and achieves a key capacity of at most one bit per photon. Under photon-starved conditions the rate of detection events is much lower than the photon generation rate, because of losses in long distance propagation and the relatively long recovery times of available single-photon detectors. Multi-bit encoding in the photon arrival times can be beneficial in such photon-starved situations. Recent security proofs indicate high-dimensional encoding in the photon arrival times is robust and can be implemented to yield high secure throughput. In this work we demonstrate entanglement-based QKD with high-dimensional encoding whose security against collective Gaussian attacks is provided by a high-visibility Franson interferometer. We achieve unprecedented key capacity and throughput for an entanglement-based QKD system because of four principal factors: Franson interferometry that does not degrade with loss; error correction coding that can tolerate high error rates; optimized time–energy entanglement generation; and highly efficient WSi superconducting nanowire single-photon detectors. The secure key capacity yields as much as 8.7 bits per coincidence. When optimized for throughput we observe a secure key rate of 2.7 Mbit s[superscript −1] after 20 km fiber transmission with a key capacity of 6.9 bits per photon coincidence. Our results demonstrate a viable approach to high-rate QKD using practical photonic entanglement and single-photon detection technologies.United States. Army Research Office (Defense Advanced Research Projects Agency. Information in a Photon (InPho) Program Grant W911NF-10-1-0416

Association Between Parkinsonism and Participation in Agriculture in Korea

BACKGROUND AND PURPOSE: Environmental factors might influence the pathogenesis of Parkinson's disease (PD) or multiple-system atrophy (MSA), and previous examinations of pesticide exposure, well-water drinking, and farming have produced inconclusive results. Because agriculture has been of considerable importance to Korean society, and hence the risk of exposure to pesticides was high in Korea, this study investigated whether such exposure is associated with elevated risks of developing PD and MSA. METHODS: Two hundred and thirty-five PD patients, 133 MSA patients, and 77 normal control subjects were examined. Data concerning environmental factors were collected by face-to-face interviews using a structured questionnaire. Odds ratios (ORs) were calculated by binary logistic regression. RESULTS: ORs for environmental risk factors for developing PD were 1.06 [95% confidence interval (CI) = 1.02-1.10] for age and 2.37 (95% CI = 1.32-4.27) for rural well-water drinking for >10 years. Smoking >10 pack-years (OR = 0.31; 95% CI = 0.11-0.64) was a preventable factor for developing PD in this study. However, no significant risk factors were identified for MSA. CONCLUSIONS: These results suggest that exposure to certain environmental risk factors plays a role in the development of PD. However, the development of MSA appears to be independent of environmental risk factors in Korean patients

Laparoscopy in management of appendicitis in high-, middle-, and low-income countries: a multicenter, prospective, cohort study.

BACKGROUND: Appendicitis is the most common abdominal surgical emergency worldwide. Differences between high- and low-income settings in the availability of laparoscopic appendectomy, alternative management choices, and outcomes are poorly described. The aim was to identify variation in surgical management and outcomes of appendicitis within low-, middle-, and high-Human Development Index (HDI) countries worldwide. METHODS: This is a multicenter, international prospective cohort study. Consecutive sampling of patients undergoing emergency appendectomy over 6 months was conducted. Follow-up lasted 30 days. RESULTS: 4546 patients from 52 countries underwent appendectomy (2499 high-, 1540 middle-, and 507 low-HDI groups). Surgical site infection (SSI) rates were higher in low-HDI (OR 2.57, 95% CI 1.33-4.99, p = 0.005) but not middle-HDI countries (OR 1.38, 95% CI 0.76-2.52, p = 0.291), compared with high-HDI countries after adjustment. A laparoscopic approach was common in high-HDI countries (1693/2499, 67.7%), but infrequent in low-HDI (41/507, 8.1%) and middle-HDI (132/1540, 8.6%) groups. After accounting for case-mix, laparoscopy was still associated with fewer overall complications (OR 0.55, 95% CI 0.42-0.71, p < 0.001) and SSIs (OR 0.22, 95% CI 0.14-0.33, p < 0.001). In propensity-score matched groups within low-/middle-HDI countries, laparoscopy was still associated with fewer overall complications (OR 0.23 95% CI 0.11-0.44) and SSI (OR 0.21 95% CI 0.09-0.45). CONCLUSION: A laparoscopic approach is associated with better outcomes and availability appears to differ by country HDI. Despite the profound clinical, operational, and financial barriers to its widespread introduction, laparoscopy could significantly improve outcomes for patients in low-resource environments. TRIAL REGISTRATION: NCT02179112

Pooled analysis of WHO Surgical Safety Checklist use and mortality after emergency laparotomy

Background The World Health Organization (WHO) Surgical Safety Checklist has fostered safe practice for 10 years, yet its place in emergency surgery has not been assessed on a global scale. The aim of this study was to evaluate reported checklist use in emergency settings and examine the relationship with perioperative mortality in patients who had emergency laparotomy. Methods In two multinational cohort studies, adults undergoing emergency laparotomy were compared with those having elective gastrointestinal surgery. Relationships between reported checklist use and mortality were determined using multivariable logistic regression and bootstrapped simulation. Results Of 12 296 patients included from 76 countries, 4843 underwent emergency laparotomy. After adjusting for patient and disease factors, checklist use before emergency laparotomy was more common in countries with a high Human Development Index (HDI) (2455 of 2741, 89.6 per cent) compared with that in countries with a middle (753 of 1242, 60.6 per cent; odds ratio (OR) 0.17, 95 per cent c.i. 0.14 to 0.21, P <0001) or low (363 of 860, 422 per cent; OR 008, 007 to 010, P <0.001) HDI. Checklist use was less common in elective surgery than for emergency laparotomy in high-HDI countries (risk difference -94 (95 per cent c.i. -11.9 to -6.9) per cent; P <0001), but the relationship was reversed in low-HDI countries (+121 (+7.0 to +173) per cent; P <0001). In multivariable models, checklist use was associated with a lower 30-day perioperative mortality (OR 0.60, 0.50 to 073; P <0.001). The greatest absolute benefit was seen for emergency surgery in low- and middle-HDI countries. Conclusion Checklist use in emergency laparotomy was associated with a significantly lower perioperative mortality rate. Checklist use in low-HDI countries was half that in high-HDI countries.Peer reviewe