Miracle-dz/UniFAR-FTUs huggingface dataset:
NABTT 0306: A randomized phase II trial of EMD 121974 in conjunction with concomitant and adjuvant temozolomide with radiation therapy in patients with newly diagnosed glioblastoma multiforme (GBM).

2001 Background: EMD 121974 (cilengitide) is a selective integrin receptor inhibitor that is well tolerated and has demonstrated biological activity in patients with malignant glioma. The objectives of this phase II trial were to determine safety when combined with chemoradiation and estimate the overall survival for two different doses in newly diagnosed GBM. METHODS A total of 112 patients were accrued onto the trial through the NABTT CNS consortium. Cilengitide was administered by one-hour infusion twice a week with 18 patients treated in a safety run-in phase of 6 patients at the tested dose levels of 500 mg, 1000 mg, and 2000 mg. After safety completion, 94 patients were randomly assigned to either 500 mg or 2000 mg groups. To date, 55 out of 112 (49%) patients have died. Overall survival was estimated using all patients in this trial regardless of their treating dose. RESULTS The median age was 55 years old (range: 22-88) and the median KPS was 90 (range: 60-100). 86 out of the 112 (76.8%) had a craniotomy as their initial surgical procedure and 25 patients (22%) had a biopsy. There were no DLTs during the safety run-in phase. The estimated median survival time is 18.9 months (95% CI: 16.3 -30.0 months) for patients treated with RT+TMZ+EMD. The trial was closed to accrual on December 31, 2007. To date, 89 out of 112 patients were alive 12 months from their initial diagnosis. The overall survival at 12 months for all patients is 79.5% (95% CI: 71-87%). MGMT methylation status and survival based on dose levels received are not currently available. CONCLUSIONS EMD 121974 (cilengitide) is well-tolerated when combined with standard chemoradiation (TMZ+RT) and may improve survival for patients newly diagnosed with GBM given the substantial differences between the estimated median survival and that seen in the EORTC study (Stupp, N Engl J Med, 2005). [Table: see text].
Supratentorial low-grade glioma in adults: an analysis of prognostic factors and timing of radiation.

PURPOSE To review the outcomes of patients with low-grade glioma diagnosed by modern imaging and treated at a center where postponing radiotherapy was common practice. METHODS We reviewed the records of patients (age > or = 18 years) with pathologically confirmed supratentorial low-grade fibrillary astrocytoma, oligodendroglioma, and mixed glioma treated at a regional cancer center in Canada between 1979 and 1995. RESULTS Median survival for the entire group (N = 167; mean age 40.6 years) was 10.5 years with 5- and 10-year survival rates of 72% and 50%, respectively. Median progression-free survival was 4.9 years with 5- and 10-year progression-free rates of 50% and 12%, respectively. Overall and progression-free survivals were longer for patients with an oligodendroglioma or mixed glioma than with astrocytoma (median 13 v 7.5 years, P = .003; progression-free 5.6 v 4.4 years, p = .054). Age at diagnosis < or = 40 years, seizures at presentation, minimal residual tumor after surgery, Karnofsky performance status > or = 70, and oligodendroglioma or mixed glioma pathology were associated with significantly longer median survival on univariate and multivariate analyses. Radiotherapy deferred until tumor progression (v immediate radiotherapy) was associated with longer survival on univariate analysis, but an imbalance in other variables accounted for this advantage such that timing of radiotherapy was not an independent (favorable or adverse) prognostic factor on multivariate analysis. CONCLUSION Patients with low-grade glioma diagnosed by modern imaging can be expected to live a long time; timing of radiotherapy may be a less important determinant of survival than nontreatment variables and residual tumor bulk.
Racial/Ethnic Differences in Stroke in Young Adults

Racial and ethnic differences in the risk of stroke are widely recognized, and these differences are even greater among younger populations. Younger adults have a lower risk of stroke; however, they represent a major public health priority as they live longer with their disabilities, have complications throughout their life, and have a longer period of time of lost productivity [1] . The report by Pathak and Sloan [2] in this issue of Neuroepidemiology presents evidence that blacks are over 3 times more likely than whites to be hospitalized for a stroke, and that Hispanics also have a higher stroke hospitalization rate as compared to whites. In addition, they found that after risk adjustment, the fatality rates for stroke are similar for blacks and whites. Interestingly, even after adjustment, Hispanic patients had a 34% decreased likelihood of dying in hospital. These findings support the idea that the excess stroke mortality in blacks [3, 4] is due to a higher incidence rate, not a higher fatality rate; therefore, it is important that research continue to explore the racial/ethnic differences in risk factors and access to care. Prior research has shown race/ethnic differences in stroke incidence in young adults among specific urban communities. Among 74 young adults, aged 20–44 years, in the Northern Manhattan Stroke Study (NOMASS) [5] , blacks had 2.4 times the risk of stroke as compared to whites. Although not statistically significant, the NOMASS findings suggest that blacks are at greater risk of stroke than whites. These findings were corroborated by similar findings in the Greater Cincinnati/Northern Kentucky region [6] , in which blacks of all younger age groups ( ! 35, 35–44, and 45–54 years) were significantly more likely to have a stroke as compared to whites [RR 2.2 (1.3–3.1), 5.0 (3.9–6.1), and 2.6 (2.0–3.2), respectively]. As part of the Baltimore-Washington Cooperative Young Stroke Study, the odds of ischemic stroke in blacks versus whites were 2.1 (95% CI, 1.2–3.6), and the odds of intracerebral hemorrhage for blacks to whites were 3.1 (95% CI, 1.3–7.4) [7] . The findings of higher stroke incidence for blacks extends beyond the United States, and is consistent with a higher incidence among other black populations. In the United Kingdom, the South London Stroke Registry found an annual incidence rate for cerebral infarction of 1.86 per 1,000 for blacks and 0.79 per 1,000 for whites among individuals age 35–64 years [8] . These higher incidence rates are similar to those of other black populations around the world including those in South Africa [9] , Libya [10] , and Martinique [11] .
Report on the observance of standards and codes (ROSC): Kingdom of Morocco

This report provides an assessment of Moroccan accounting and auditing standards and practices, and the institutional capacity necessary to ensure high-quality financial reporting. The law gives accounting standard-setting responsibility to the National Accounting Council (Conseil National de la Comptabilite). Since the Council was established in 1989, Moroccan accounting standards have improved greatly. However, further progress is impeded by weaknesses in the accounting standard-setting process and, more so, by implementation issues. The Bank Al-Maghrib, Insurance and Social Welfare Directorate (Direction des Assurances et de la Prevoyance Sociales), and Securities Commission (Conseil Deontologique des Valeurs Mobilieres) are responsible for monitoring the quality of financial information and the enforcement of accounting standards for credit institutions, insurance companies, and listed companies, respectively. While the Bank Al-Maghrib has established an institutional framework for bank monitoring that is more advanced than that of other sectors, the overall design and implementation of the three supervisory frameworks need improvement. The legislative framework for the Moroccan accounting profession is adequate. However, significant implementation issues exist, such as the absence of a quality assurance system and the lack of continuing professional education. Moroccan auditing standards are largely inspired by the International Standards on Auditing (IAS). However, the omission of certain standards weakens the Moroccan auditing framework. The large number of chartered accountants that do not even observe Moroccan auditing standards exacerbates this issue. While financial statements in Morocco generally include most of the information necessary to analyze the financial status of a company, certain lesser disclosure standards as compared to the IAS reduce the usefulness and transparency of Moroccan financial reports. Moreover, financial information is not readily available, as the mechanisms to publish statements are inefficient. The policy recommendations in this report focus on strengthening the enforcement of established accounting and auditing requirements, as well as supporting the initiatives that Morocco has been implementing over the last ten years.
Short-term outcomes after surgery for colorectal cancer in Turkish patients aged 70 and above.

BACKGROUND/AIMS We aimed to evaluate the impact of age on short-term surgical outcomes and to investigate the risk factors for postoperative mortality in 660 Turkish colorectal cancer patients. METHODS Between January 2002 and January 2007, 660 consecutive patients who were operated for colorectal cancer at our institution were enrolled in this study. The patients were divided into two groups as: a younger group (<70 years) and an older group (≥70 years). Patient data were recorded prospectively with the use of specially designed forms. Variables and short-term patient results were compared. RESULTS American Society of Anesthesiologists (ASA) scores were significantly higher and albumin levels were lower in the older group compared with the younger group (p<0.05). Morbidity and mortality rates were 16.8% (83/494) and 2.6% (13/494) in the younger group and 22.9% (38/166) and 3.0% (5/166) in the older group, respectively. These differences in rates were not statistically significant. ASA score (ASA 4) and non-resective procedures were found to be independent risk factors for mortality. CONCLUSIONS Age should not be regarded as a reason for limited surgery. Elderly patients should undergo the same standard surgical approach as younger patients. The patient's general state of health is more effective on postoperative mortality.
Role of human papillomavirus testing and cytology in follow‐up after conization

Adequate follow‐up of women who have undergone conization for high‐grade cervical lesions is crucial in cervical cancer screening programs. We evaluated the performance of testing for high‐risk human papillomavirus (HPV) types, cytology alone, and combined testing in predicting cervical intraepithelial neoplasia grade 2 or worse (CIN2+) after conization.
Graded Exercise Therapy Guided Self-Help Trial for Patients with Chronic Fatigue Syndrome (GETSET): Protocol for a Randomized Controlled Trial and Interview Study

Background Chronic fatigue syndrome, also known as myalgic encephalomyelitis (CFS/ME), is characterized by chronic disabling fatigue and other symptoms, which are not explained by an alternative diagnosis. Previous trials have suggested that graded exercise therapy (GET) is an effective and safe treatment. GET itself is therapist-intensive with limited availability. Objective While guided self-help based on cognitive behavior therapy appears helpful to patients, Guided graded Exercise Self-help (GES) is yet to be tested. Methods This pragmatic randomized controlled trial is set within 2 specialist CFS/ME services in the South of England. Adults attending secondary care clinics with National Institute for Health and Clinical Excellence (NICE)-defined CFS/ME (N=218) will be randomly allocated to specialist medical care (SMC) or SMC plus GES while on a waiting list for therapist-delivered rehabilitation. GES will consist of a structured booklet describing a 6-step graded exercise program, supported by up to 4 face-to-face/telephone/Skype™ consultations with a GES-trained physiotherapist (no more than 90 minutes in total) over 8 weeks. The primary outcomes at 12-weeks after randomization will be physical function (SF-36 physical functioning subscale) and fatigue (Chalder Fatigue Questionnaire). Secondary outcomes will include healthcare costs, adverse outcomes, and self-rated global impression change scores. We will follow up all participants until 1 year after randomization. We will also undertake qualitative interviews of a sample of participants who received GES, looking at perceptions and experiences of those who improved and worsened. Results The project was funded in 2011 and enrolment was completed in December 2014, with follow-up completed in March 2016. Data analysis is currently underway and the first results are expected to be submitted soon. Conclusions This study will indicate whether adding GES to SMC will benefit patients who often spend many months waiting for rehabilitative therapy with little or no improvement being made during that time. The study will indicate whether this type of guided self-management is cost-effective and safe. If this trial shows GES to be acceptable, safe, and comparatively effective, the GES booklet could be made available on the Internet as a practitioner and therapist resource for clinics to recommend, with the caveat that patients also be supported with guidance from a trained physiotherapist. The pragmatic approach in this trial means that GES findings will be generalizable to usual National Health Service (NHS) practice. Trial Registration International Standard Randomized Controlled Trial Number (ISRTCTN): 22975026; http://www.isrctn. com/ISRCTN22975026 (Archived by WebCite at http://www.webcitation.org/6gBK00CUX)
What Do We Know About the Tax Planning of German‐Based Multinational Firms?

Research results confirm the existence of various forms of international tax planning by multinational firms. Prominent examples for firms employing tax avoidance strategies are Amazon, Google and Starbucks. Increasing availability of administrative data for Europe has enabled researchers to study behavioural responses of European multinationals to taxation. The present paper summarizes what we can learn from these recent studies in general and about German multinationals in particular.
Comparative pulmonary toxicity of inhaled nickel nanoparticles; role of deposited dose and solubility

In this pilot study, we investigated which physicochemical properties of nickel hydroxide nanoparticles (nano-NH) were mainly responsible in inducing pulmonary toxicity. First, we studied the role of nickel ions solubilized from nano-NH by comparing the toxic effects of nano-NH to those of readily soluble nickel sulfate nanoparticles (nano-NS). Additionally, to test whether there was a non-specific stress response due to particle morphology, we compared the toxicity of nano-NH with that of carbon nanoparticles (nano-C) and titanium dioxide nanoparticles (nano-Ti), both of which had similar physical properties such as particle size and shape, to nano-NH. We exposed mice to each type of nanoparticles for 4 h via a whole-body inhalation system and examined oxidative stress and inflammatory responses in the lung. We also determined the lung burden and clearance of Ni following nano-NH and nano-NS exposures. The results showed that lung deposition of nano-NH was significantly greater than that of nano-NS and nano-NH appeared to have stronger inflammogenic potential than nano-NS even when lung Ni burden taken into consideration. This suggests that the toxicity of nano-NH is not driven solely by released Ni ions from deposited nano-NH particles. However, it is unlikely that the greater toxic potential of nano-NH is attributable to a generic stress response from any nanoparticle exposure, since nano-C and nano-Ti did not elicit toxic responses similar to those of nano-NH. These results indicate that the observed pulmonary toxicity by inhaled nano-NH were chemical-specific and deposited dose and solubility are key factors to understand toxicity induced by nano-NH.
The Effect of Management Incentives and Audit Committee Quality on Internal Auditors' Planning Assessments and Decisions

We examine the sensitivity of internal auditors' fraud risk assessments and audit effort decisions (i.e., budgeted hours) to variations in management's incentives to intentionally misstate their financial position, and in the quality of a firm's audit committee. Internal auditors are an integral part of an organization's monitoring scheme and it is important to understand how, and how well, their judgments are influenced by factors known to be associated with fraudulent financial reporting. We hypothesize that internal auditors' fraud risk judgments and audit effort decisions will vary with management incentives and quality of audit committee, consistent with documented archival evidence and professional prescriptions. The experimental results, based on responses from 60 internal auditors completing a hypothetical case regarding a potential acquisition target, indicate that internal auditors' fraud risk assessments are responsive to management incentives and variations in the quality of the audit committee. Our results also indicate that internal auditors' budgeted audit hours are sensitive to variations in management incentives to misreport financial information, but are not sensitive to variations in audit committee quality. This latter result implies that internal auditors are aware that stronger audit committees decrease the risk of fraudulent financial reporting, but do not use that knowledge to reduce fraud related work. These results generally hold for a second experiment in which another group of internal auditors was asked to complete the same hypothetical case, but rather than evaluating an acquisition target, they made planning judgments for an audit area of the company in which they were employed. Thus, the results generally hold whether the internal auditors are performing due diligence for a possible acquisition or are auditing their own organization where they may have incentives congruent with organization management, and may have familiarity with the audit committee.
What Do Credit Markets Tell Us About the Speed of Adjustment?

This article proposes a methodology to infer investors’ expectations about the speed at which firms adjust to their target leverage. We find that in the long run bond and CDS investors expect leverage to converge towards a target as suggested by the tradeoff theory. On average, the credit markets imply a fairly rapid annual speed of adjustment of 26%. However, we also find strong support that in the short run the expected adjustment process implicit in the prices of credit instruments is affected by transaction costs, pecking order, and market timing. Overall, we show that one can learn about capital structure speed of adjustment not just from realized leverage changes, but also from expectations embedded in market prices.
Cytokine Levels and Phagocytic Activity in Patients with Alzheimer’s Disease

Background: Clinical observations indicate that patients with Alzheimer’s disease show a greater susceptibility to infections. One possible explanation is that this predisposition is due to alterations in their immune system. Objective: To investigate this assumption, pro- and anti-inflammatory cytokines, as well as the phagocytic activity and superoxide anion generation was examined in aged individuals with and without Alzheimer’s disease. Methods: The production of IL-1β, IL-2, IL-6, TNFα and IL-10 by peripheral blood mononuclear cells from 12 patients with Alzheimer’s disease was compared with that of 12 age-matched individuals without any signs of dementia and 12 middle-aged healthy volunteers who served as an additional control. The engulfing capacity of the phagocytic cells was detected by counting cells containing latex beads and the number of particles internalized by each individual cell. Results: The secretion of IL-2 was markedly low in the demented patients, compared with both elderly and middle-aged subjects. IL-1β and TNFα production was similar in the individuals of the 3 groups. The production of IL-6 and IL-10 was significantly lower when compared to that of the middle-aged, but did not differ between the elderly patients with and without dementia. The phagocytic function of both polymorphonuclear cells and monocytes was decreased in individuals of the elderly groups with a low number of engulfed latex particles by each individual polymorphonuclear cell. The production of superoxide anions was increased only by monocytes from the elderly groups. Conclusions: The results suggest that although the impaired immune function in patients with Alzheimer’s disease is related to the aging process, the significant low IL-2 production in these patients may play a role in their increased susceptibility to infections.
A Framework for the Analysis of the Performance and Sustainability of Subsidized Microfinance Organizations with Application to Bancosol of Bolivia and Grameen Bank of Bangladesh

In the next ten years, society will spend more than $20 billion on microfinance organizations (MFOs). Are MFOs the best way to help the poor? Will donors see MFOs as a good development gamble? Will MFOs reward workers well? Will investors buy MFOs and start new ones from scratch? I suggest a framework to help answer these questions with numbers. Performance is meeting goals. Sustainability is meeting goals now and in the long term. An MFO has six groups of stakeholders: society, the poor, poor customers, donors, workers, and investors. Each group constrains the rest. Each group has its own goals and thus its own measures of performance. For society, a good MFO makes more social benefits than social costs. For the poor, a good MFO is the best use of the funds in the budget earmarked to help the poor. It costs more to measure benefits than to measure costs. Cost-effectiveness analysis can help to judge whether unmeasured benefits could exceed measured costs. For poor customers, a good MFO gets repeated use. For donors, a good MFO uses public funds to attract market funds. For the workers of an MFO, a good MFO means a good job. Such an MFO would not shrink if donors withdrew support. For investors, good performance means a market return. I use the framework with two of the best MFOs in the world, BancoSol in Bolivia and Grameen Bank in Bangladesh. I judge both to have been worthwhile. They used public funds to help the poor more than the marginal development project. The net present cost of BancoSol for the poor through 1987-1996 as seen in 1987 was about 6 cents per dollar year of debt produced. At Grameen, the net present cost to the poor through 1983-1994 as seen from 1983 was about $8 per year of membership produced. The customers at both BancoSol and Grameen repeat, and the workers at the both banks have good jobs. BancoSol attracts market funds, and Grameen does not. This suggests that investors may buy the best MFOs once start-up costs are sunk. But investors do not start the best MFOs, and much less the worse MFOs, from scratch. At least the best MFOs are worthwhile. The rest may still waste public funds meant to help the poor. Cost-effectiveness analysis is a cheap tool to help judge.