Activity of high-dose epirubicin combined with gemcitabine in advanced non-small-cell lung cancer: a multicenter phase I and II study

The aim of the study was to evaluate efficacy and tolerance of epirubicin and gemcitabine as first-line chemotherapy in patients with advanced non-small-cell lung cancer. A phase I study was performed with the combination of escalating doses of epirubicin intravenously on day 1 and a fixed dose of gemcitabine on days 1 and 8 of a 21-day cycle. Eighteen patients were included in the phase I part of the study before the maximum tolerated dose was found. Dose-limiting toxicity was febrile neutropenia. The phase II part of the study was continued with epirubicin 100 mg m−2on day 1 and gemcitabine 1125 mg m−2on days 1 and 8 of a 21-day cycle. Forty-three chemotherapy-naive patients were included. The median age of the patients was 60 years (range 26–75). Most patients (74%) were in stage IV. Granulocytopenia CTC grade 4 occurred in 32.5% and thrombocytopenia grade 4 in 11.6% of cycles. Febrile neutropenia occurred in six patients. Non-haematological toxicity was mainly mucositis CTC grade 2 and 3 in 35% of patients. The tumour response rate was 49% (95% confidence interval (CI) 35–63%). The median survival time for the patients was 42 weeks (95% CI 13–69). © 2000 Cancer Research Campaig

Institutions for Asian Connectivity

To make Asia more economically sustainable and resilient against external shocks, regional economies need to be rebalanced toward regional demand- and trade-driven growth through increased regional connectivity. The effectiveness of connectivity depends on the quality of hard and soft infrastructure. Of particular importance in terms of soft infrastructure which makes hard infrastructure work are the facilitating institutions that support connectivity through appropriate policies, reforms, systems, and procedures and through promoting effective coordination and cooperation. Asia has many overlapping subregional institutions involved in national and regional energy, transport, and telecommunications infrastructure connectivity. However, these institutions are characterized as being less effective, informal, and lacking a clear and binding system of rules and policies. This paper draws linkages between connectivity, growth and development, governance, and institutions. It details the benefits the region could achieve by addressing needed connectivity enhancements and the connectivity and financing challenges it faces. In addition, it presents various institutional options for regional infrastructure financing. To build seamless Asian connectivity, Asia needs an effective, formal, and rules-based institutional framework. The paper presents a new institutional framework together with the organizational structures of two new regional institutional mechanisms, namely the Pan-Asian Infrastructure Forum and the Asian Infrastructure Fund

Letter from Frank Nabers, Gager Lime Manufacturing Company, Sherwood, Tennessee, to J.H. Woodward, Woodward Iron Company, Woodward, Alabama, April 8, 1940

This is an item in the Woodward Family Papers collection

Letter from Joseph H. Woodward, II, to Frank Nabers, Gager Lime Manufacturing Company, Sherwood, Tennessee, March 29, 1940

This is an item in the Woodward Family Papers collection

A beta misfolding in blood plasma is inversely associated with body mass index even in middle adulthood

Background To understand the potential for early intervention and prevention measures in Alzheimer's disease, the association between risk factors and early pathological change needs to be assessed. Hence, the aim of this study was to determine whether risk factors of Alzheimer's clinical syndrome (clinical AD), such as body mass index (BMI), are associated with A beta misfolding in blood, a strong risk marker for AD among older adults. Methods Information on risk factors and blood samples were collected at baseline in the ESTHER study, a population-based cohort study of older adults (age 50-75 years) in Germany. A beta misfolding in blood plasma was analyzed using an immuno-infrared-sensor in a total of 872 participants in a nested case-control design among incident dementia cases and matched controls. Associations between risk factors and A beta misfolding were assessed by multiple logistic regression. For comparison, the association between the risk factors and AD incidence during 17 years of follow-up was investigated in parallel among 5987 cohort participants. Results An inverse association with A beta misfolding was seen for BMI at age 50 based on reported weight history (aOR 0.64, 95% CI 0.43-0.96, p = 0.03). Similar but not statistically significant associations were seen for BMI at baseline (i.e., mean age 68) and at age 40. No statistically significant associations with A beta misfolding were found for other risk factors, such as diabetes, smoking, and physical activity. On the other hand, low physical activity was associated with a significantly reduced risk of developing clinical AD compared to physical inactivity. Conclusions Our results support that AD pathology may be detectable and associated with reduced weight even in middle adulthood, many years before clinical diagnosis of AD. Physical activity might reduce the risk of onset of AD symptoms

A beta misfolding in blood plasma measured by immuno-infrared-sensor as an age-independent risk marker of Alzheimer's disease

Introduction Determining potential risk factors of amyloid beta (A beta) misfolding in blood, a risk marker for clinical Alzheimer's disease (AD), could have important implications for its utility in future research and clinical settings. Methods Participants aged 50 to 75 years attending a general health examination were recruited for a prospective community-based cohort study in Saarland, Germany, in 2000 to 2002. For these analyses, participants with available A beta misfolding measurements and clinical AD information at 17-year follow-up were included (n = 444). Results Age did not show any association with A beta misfolding in plasma; however, a strong association of both age and A beta misfolding with the incidence of clinical AD was evident. Education and cardiovascular diseases were likewise not associated with A beta misfolding. Discussion Structural measurement of A beta misfolding in blood plasma is an age-independent risk marker of clinical AD among older adults, supporting that risk of clinical AD is already largely determined before older adulthood

Prediction of Alzheimer's disease diagnosis within 14 years through A beta misfolding in blood plasma compared to APOE4 status, and other risk factors

Introduction: Alzheimer's disease (AD) has a long prodromal stage and identifying high-risk individuals is critical. We aimed to investigate the ability of A beta misfolding in blood plasma, APOE4 status, and dementia risk factors to predict diagnosis of AD. Methods: Within a community-based cohort, A beta misfolding in plasma measured by immuno-infrared sensor and APOE genotypewere determined at baseline in 770 participants followed over 14 years. Associations between A beta misfolding, APOE4, and other predictors with clinical AD, vascular dementia, and mixed dementia diagnoses were assessed. Results: A beta misfolding was associated with a 23-fold increased odds of clinical AD diagnosis within 14 years. No association was observed with vascular dementia/mixed dementia diagnoses. APOE4-positive participants had a 2.4-fold increased odds of clinical AD diagnosis within 14 years. Discussion: A beta misfolding in blood plasma was a strong, specific risk prediction marker for clinical AD evenmany years before diagnosis in a community-based setting

Genetic predisposition, A beta misfolding in blood plasma, and Alzheimer's disease

Alzheimer's disease is highly heritable and characterized by amyloid plaques and tau tangles in the brain. The aim of this study was to investigate the association between genetic predisposition, A beta misfolding in blood plasma, a unique marker of Alzheimer associated neuropathological changes, and Alzheimer's disease occurrence within 14 years. Within a German community-based cohort, two polygenic risk scores (clinical Alzheimer's disease and A beta (42) based) were calculated, APOE genotype was determined, and A beta misfolding in blood plasma was measured by immuno-infrared sensor in 59 participants diagnosed with Alzheimer's disease during 14 years of follow-up and 581 participants without dementia diagnosis. Associations between each genetic marker and A beta misfolding were assessed through logistic regression and the ability of each genetic marker and A beta misfolding to predict Alzheimer's disease was determined. The Alzheimer's disease polygenic risk score and APOE epsilon 4 presence were associated to A beta misfolding (odds ratio, 95% confidence interval: per standard deviation increase of score: 1.25, 1.03-1.51; APOE epsilon 4 presence: 1.61, 1.04-2.49). No association was evident for the A beta polygenic risk score. All genetic markers were predictive of Alzheimer's disease diagnosis albeit much less so than A beta misfolding (areas under the curve: A beta polygenic risk score: 0.55; AD polygenic risk score: 0.59; APOE epsilon 4: 0.63; A beta misfolding: 0.84). Clinical Alzheimer's genetic risk was associated to early pathological changes (A beta misfolding) measured in blood, however, predicted Alzheimer's disease less accurately than A beta misfolding itself. Genetic predisposition may provide information regarding disease initiation, while A beta misfolding could be important in clinical risk prediction