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"Chan, Robert"
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The cross-sectional and longitudinal relationship of diabetic retinopathy to cognitive impairment: a systematic review and meta-analysis
Objectives
To establish a potential relationship between diabetic retinopathy (DR) and different stages of cognitive impairment
Methods
Literature searches were conducted on PubMed and EMBASE, with keywords “diabetic retinopathy” and “cognitive impairment”. Inclusion criteria were original human studies, and English language. Quality of studies was assessed by the Newcastle-Ottawa Quality Assessment (NOSGEN). The register number of this study on the International Prospective Register of Systematic Reviews (PROSPERO) is CRD42021236747. The main outcome measures were odds ratios (OR) and risk ratios (RR) for cross-sectional and longitudinal studies, respectively. Meta-regression was performed to evaluate the effects of potential moderator variables, including, age, onset age of diabetes mellitus (DM), duration of DM, and HbA1c.
Results
Twenty-five studies (17 cross-sectional and 8 longitudinal studies) with a total of 1,963,914 subjects, were included. Among the cross-sectional studies, the pooled ORs of any cognitive impairment, early stage of cognitive impairment and dementia in subjects with DR (95% confidence interval) were 1.48 (1.08–2.02), 1.59 (1.01–2.51), and 1.13 (0.86–1.50), respectively. Among the longitudinal studies, the pooled RRs of any cognitive impairment, early stage of cognitive impairment, and dementia in subjects with DR (95% confidence interval) were 1.35 (1.12–1.65), 1.50 (1.06–2.12), and 1.31 (1.03–1.66), respectively. Meta-regression showed age, onset age of DM, duration of DM, and glycated hemoglobin (HbA1c) were not statistically associated with the outcomes.
Conclusions
The presence of DR in DM patients indicates both higher odds of prevalent cognitive impairment and escalated risks of developing cognitive impairment in the future.
Journal Article
The dam keeper. Book three, Return from the shadows
\"Sunrise Valley is without a dam keeper, and time is running out. In less than twenty-four hours, the poisonous tidal wave of black fog will descend on Pig's home. While Fox, Hippo, and Van hurry east to warn the townspeople, Pig ventures on his own path\"--Publisher marketing.
BOOK
Parafoveal processing of repeated words during reading
In an eye-tracking experiment during reading, we examined the repetition effect, whereby words that are repeated in the same paragraph receive shorter fixation durations. Target words that were either high-frequency or low-frequency words and of which the parafoveal preview was either correct or with all letters replaced were embedded three times in the same paragraph. Shorter fixation times and higher skipping rates were observed for high-frequency compared to low-frequency words, words for which the parafoveal preview was correct versus incorrect, and as the word was being repeated more often. An interaction between frequency and repetition indicated that the reduction in fixation times due to repetition was more pronounced for low-frequency words. We also observed influences of word repetition on parafoveal processing, as repeated words were skipped more often. An interaction between parafoveal preview and repetition indicated an absent repetition effect when the preview was incorrect, but this effect was short lived, as it was restricted to the first fixation duration on the target word.
Journal Article
On explicit two-derivative Runge-Kutta methods
The theory of Runge-Kutta methods for problems of the form
y
′ =
f
(
y
) is extended to include the second derivative
y
′′ =
g
(
y
): =
f
′(
y
)
f
(
y
). We present an approach to the order conditions based on Butcher’s algebraic theory of trees (Butcher, Math Comp 26:79–106,
1972
), and derive methods that take advantage of cheap computations of the second derivatives. Only explicit methods are considered here where attention is given to the construction of methods that involve one evaluation of
f
and many evaluations of
g
per step. Methods with stages up to five and of order up to seven including some embedded pairs are presented. The first part of the paper discusses a theoretical formulation used for the derivation of these methods which are also of wider applicability. The second part presents experimental results for non-stiff and mildly stiff problems. The methods include those with the computation of one second derivative (plus many first derivatives) per step, and embedded methods for changing stepsize as well as those involving one first derivative (plus many second derivatives) per step. The experiments have been performed on standard problems and comparisons made with some standard explicit Runge-Kutta methods.
Journal Article
A positron emission tomography imaging study to confirm target engagement in the lungs of patients with idiopathic pulmonary fibrosis following a single dose of a novel inhaled αvβ6 integrin inhibitor
Background
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease with poor prognosis and a significant unmet medical need. This study evaluated the safety, pharmacokinetics (PK) and target engagement in the lungs, of GSK3008348, a novel inhaled alpha-v beta-6 (αvβ6) integrin inhibitor, in participants with IPF.
Methods
This was a phase 1b, randomised, double-blind (sponsor unblind) study, conducted in the UK (two clinical sites, one imaging unit) between June 2017 and July 2018 (NCT03069989). Participants with a definite or probable diagnosis of IPF received a single nebulised dose of 1000 mcg GSK3008348 or placebo (ratio 5:2) in two dosing periods. In period 1, safety and PK assessments were performed up to 24 h post-dose; in period 2, after a 7-day to 28-day washout, participants underwent a total of three positron emission tomography (PET) scans: baseline, Day 1 (~ 30 min post-dosing) and Day 2 (~ 24 h post-dosing), using a radiolabelled αvβ6-specific ligand, [
18
F]FB-A20FMDV2. The primary endpoint was whole lung volume of distribution (V
T
), not corrected for air volume, at ~ 30 min post-dose compared with pre-dose. The study success criterion, determined using Bayesian analysis, was a posterior probability (true % reduction in V
T
> 0%) of ≥80%.
Results
Eight participants with IPF were enrolled and seven completed the study. Adjusted posterior median reduction in uncorrected V
T
at ~ 30 min after GSK3008348 inhalation was 20% (95% CrI: − 9 to 42%). The posterior probability that the true % reduction in V
T
> 0% was 93%. GSK3008348 was well tolerated with no reports of serious adverse events or clinically significant abnormalities that were attributable to study treatment. PK was successfully characterised showing rapid absorption followed by a multiphasic elimination.
Conclusions
This study demonstrated engagement of the αvβ6 integrin target in the lung following nebulised dosing with GSK3008348 to participants with IPF. To the best of our knowledge this is the first time a target-specific PET radioligand has been used to assess target engagement in the lung, not least for an inhaled drug.
Trial registration
clinicaltrials.gov:
NCT03069989
; date of registration: 3 March 2017.
Journal Article
سر الثراء = The secret to wealth : دراسات
في هذا الكتاب المذهل سر الثراء الجزء الثالث قام كلا من سونيل تولسياني وبراين تريسي بجمع قادة اليوم القادمين من جميع أنحاء العالم للكشف عن إستراتيجياتهم المتطورة لمساعدتك على أن تصبح ثريا بشكل كبير. داخل هذه الصفحات، ستجد تقنيات وأدوات لتغيير الحياة لتحقيق أحلامك. سواء كنت تريد أن تصبح رائد أعمال ومليونير فائق الثروة، أو تشتري العقارات دون استخدام أموالك الخاصة، أو تتقاعد ثريا في سن أصغر، أو تقوم بجذب عملائك ذوي الدخل المرتفع، أو إعداد نفسك لتربح مبالغ ضخمة من الدخل السلبي، فهذا الكتاب مناسب لك تماما.
Book
Computed tomography interobserver agreement in the assessment of aneurysmal subarachnoid hemorrhage and predictors for clinical outcome
BackgroundThe severity of aneurysmal subarachnoid hemorrhage (SAH) is often assessed by the clinical state of the patient on presentation, but radiological evaluation of the extent of hemorrhage has rarely been examined in the literature. Several CT scan based grading systems exist yet only a few studies have investigated interobserver agreement. We evaluated five radiological grading systems and assessed their clinical value for early prognostication.MethodologyThis was a retrospective study of patients diagnosed with aneurysmal SAH with a CT scan performed within 72 hours of symptom onset. Four independent observers, blinded to patient outcome, evaluated each scan using the five grading systems. A separate assessor determined 6 month outcome from clinical records. The primary outcome was interobserver agreement for each grading system using the Fleiss κ statistic. The secondary endpoint was the 6 month modified Rankin Scale score, with poor outcome defined as a score of 4–6.Results165 patients with a mean age of 59 years were assessed. Interobserver agreement for the Fisher, modified Fisher, Claassen, Barrow Neurological Institute, and Hijdra grading systems were as follows: k=0.53 (moderate), k=0.42 (moderate), k=0.38 (mild), k=0.20 (poor), and k=0.66 (good), respectively. The only independent clinical risk factor for poor outcome was a World Federation of Neurological Surgeons (WFNS) grade of 4 or 5 (adjusted OR 6.55; p<0.05). After adjusting for confounders, Fisher grade 4 (adjusted OR 17.84), modified Fisher grade 4 (adjusted OR 5.65), and Hijdra grade 3 (adjusted OR 3.34) were associated with poor outcome. Receiver operator characteristic analysis revealed that the Hijdra grading system (area under the curve=0.76) was more predictive of outcome compared with the Fisher and modified Fisher systems. A Hijdra cut-off score of 22 was associated with poor outcome (adjusted OR 5.92).ConclusionsThe Hijdra grading system had the best interobserver agreement and was a better independent early predictor for 6 month clinical outcome than the other systems. A Hijdra score ≥22 was associated with poor outcome.
Journal Article