Miracle-dz/UniFAR-FTUs huggingface dataset:
Adjuvant Therapy for Pancreatic Cancer: No 'Definite' Standard

Despite attempted curative resection of localized adenocarcinoma of the pancreas, most patients experience a recurrence and die of their disease. The Gastrointestinal Tumor Study Group, European Organisation for Research and Treatment of Cancer, and European Study Group for Pancreatic Cancer trials have suggested the benefit of adjuvant therapy. However, the relatively few randomized trials available have not established a definite standard of care due to study limitations. Although these trials, and the recently published Charite Onkologie (CONKO)-001 trial, have shown a definite advantage of adjuvant chemotherapy, the most effective chemotherapy and the role of radiation therapy remain unclear. This review will discuss the data available from reported trials of adjuvant and neoadjuvant therapy in pancreatic cancer, address the issues leading to the ongoing controversies, and consider future directions for clinical trials.
Stratification of SNOT-22 scores into mild, moderate or severe and relationship with other subjective instruments.

AIMS AND OBJECTIVES The European Position Paper on Rhinosinusitis and Nasal Polyps provides treatment algorithms based on the mild/moderate/severe (MMS) classification. To date there has been no statistically validated stratification of the SNOT-22 score according to this classification. METHODS 65 consecutive patients diagnosed with CRS completed a SNOT-22, VAS and rated their symptoms according to MMS and impact on quality of life. RESULTS The median SNOT 22 scores varied between the 3 MMS categories. The interquartile ranges for the respective MMS groups were: Mild 8-17, Moderate 22.5-48, Severe 54-83. Median values for the respective MMs groups were: Mild 12, Moderate 36 and Severe 66. 15.38% of patients in the Mild category, 95.24% in the Moderate category and 100% in the Severe category feel their QoL is affected. There was a strongly positive correlation between the SNOT-22 and VAS scores. CONCLUSION We propose a statistically validated definition for stratification of the SNOT-22, with Mild being defined on the SNOT-22 score as 8-20 inclusive, Moderate as >20-50 and Severe as >50.
Biochemical markers and the FDA Critical Path: How biomarkers may contribute to the understanding of pathophysiology and provide unique and necessary tools for drug development

The aim of this review is to discuss the potential usefulness of a novel class of biochemical markers, neoepitopes, in the context of the US Food and Drug Administration (FDA) Critical Path Initiative, which emphasizes biomarkers of safety and efficacy as areas of pivotal interest. Examples of protein degradation fragments – neoepitopes – that have proven useful for research on bone and cartilage are collagen type I and collagen type II degradation products, respectively. These markers have utility in the translational approach, as they can be used to estimate safety and efficacy in both preclinical models and clinical settings. Biochemical markers of tissue degradation may provide optimal tools, which in combination with other techniques, prove essential to drug discovery and development.
Corporate Payout Policy in Founder and Family Firms

This paper investigates the tax and agency explanations of corporate payout policy by investigating the likelihood, the level and the method of payout in founder and family firms. Controlling founders and families are both subject to the tax disadvantage of dividends arising from their substantial shareholdings, but family firms are arguably subject to more severe agency conflicts than founder firms due to their susceptibility to wasteful expenditure and the adverse effects of intra-family conflicts. Results indicate that founder firms on average are less likely and pay a lower level of dividends than family firms. Moreover, founder firms prefer share repurchase over dividends as the main method of payout whereas family firms prefer dividends over share repurchase. Overall, our findings are consistent with the agency explanation of corporate payout policy.
[Severe vitamin-D deficiency in more than half of the immigrant pregnant women of non-western origin and their newborns].

OBJECTIVE To determine the prevalence of vitamin-D deficiency in pregnant women and their newborns. DESIGN Descriptive. METHOD During the period of one year (April 2004-April 2005) 545 pregnant women of Dutch/European origin and 131 pregnant women of non-Western origin (mainly Turkish and Moroccan) were studied during their 10th and/or 30th week of pregnancy for calcidiol (vitamin-D) and calcium levels. The study took place in the Amersfoort region in the center of the Netherlands. In addition, cord blood samples were taken for vitamin-D and calcium levels from the 442 and 81 Dutch/European and non-Western newborns respectively. RESULTS A severe deficiency was found (calcidiol < 20 nmol/l) in 55% of non-European women compared to 5% of Dutch/West-European women. From the cord blood samples, a severe vitamin-D deficiency (calcidiol < 13 nmol/l) was found in 54% of the newborns of non-European origin compared to 6% of the Dutch/West-European newborns. Vitamin-D concentrations in pregnant women at term were strongly correlated to the concentrations in the newborns' cord blood (R = 0.84). The calcium levels of pregnant women and newborns did not differ significantly between both population groups. CONCLUSION More than half of the non-European pregnant women and their newborns had a severe vitamin-D deficiency. Screening for vitamin D deficiency and adequate suppletion for this risk group appears to be necessary. The causes and consequences of vitamin-D deficiency in pregnancy are discussed.
Angiotensin-converting enzyme inhibition restores flow-dependent and cold pressor test-induced dilations in coronary arteries of hypertensive patients.

BACKGROUND Cold pressor test (CPT)-induced and flow-dependent epicardial coronary artery dilations are impaired in patients with hypertension. ACE inhibition can attenuate sympathetic coronary constriction and potentiate or restore endothelium-dependent relaxations. This study was designed to determine whether the ACE inhibitor perindoprilat can restore normal coronary dilative responses in hypertensive patients. METHODS AND RESULTS Coronary vasomotor responses to CPT and to maximal increase of blood flow induced by papaverine were studied in 10 untreated patients with essential hypertension, no other risk factors, and angiographically normal coronary arteries before and after intravenous ACE inhibition by perindoprilat. Diameters of proximal and distal left anterior descending (LAD) and circumflex coronary arteries were measured by quantitative angiography. Estimates of coronary blood flow and resistance index were calculated with an intracoronary Doppler catheter in the distal LAD. Perindoprilat did not modify the hemodynamic responses to CPT and papaverine. In response to CPT, perindoprilat changed the epicardial coronary constriction (-8.4 +/- 5.8%, P < .001) into a significant dilation (+12.0 +/- 6.4%, P < .001). Perindoprilat significantly increased the coronary blood flow (from 33.7 +/- 10.0 to 57.9 +/- 20.5 mL/min, P < .01) and enhanced the decrease in coronary resistance (from 4.28 +/- 1.27 to 2.96 +/- 0.84 mm Hg.mL-1.min-1, P < .001) caused by CPT. Flow-dependent dilation of the proximal LAD was abolished in the control condition and was restored after perindoprilat (12.6 +/- 4.7%, P < .001). CONCLUSIONS ACE inhibition restored CPT-induced and flow-mediated coronary artery dilations in patients with essential hypertension. These results indicate that impaired coronary vasomotor responses may be reversible in recently diagnosed hypertension.
The Organizational Advantage? Social Capital, Gender, and Small Business Owners' Access to Resources

Under the competitive conditions of modern economies, the resources directly controlled by owners frequently are not sufficient to ensure their small businesses' survival and growth. Instead, owners often need to supplement what they personally control by using their social capital – resources embedded in their social relations with others-to obtain financing, expert advice, and other resources. In particular, business owners may be able to create and enhance their social capital by joining and participating in voluntary associations, thus making connections beyond their immediate circle of relationships. Voluntary associations present opportunities for members to make connections with persons unlikely to be encountered otherwise. Therefore, membership in organizations may increase the heterogeneity of owners' personal networks. Increased heterogeneity, in turn, may lead to improved access to resources, and as a result, enhance the odds of success and survival for owners' businesses. However, benefits from social capital created through organizational memberships may flow unevenly to men and women. Using data from the Entrepreneurial Development Study, we examine the contribution that voluntary association membership and participation make to small business owners' access to critical organizational resources. Our results indicate that memberships in instrumental associations and intensive organizational involvement increase business owners' odds of gaining access to some resources, such as expert advice. But, the overall impact of membership is limited. We also show that women do not suffer any notable disadvantages in this process, compared to men. Indeed, memberships in several types of instrumental associations actually appear to benefit women more than men. 3 Under the competitive conditions of modern economies, the resources directly controlled by owners frequently are not sufficient to ensure their small businesses' survival and growth (Aldrich, 1999: 82-112). Instead, owners often need to supplement what they personally control by using their social capital – resources embedded in their social relations with others-to obtain financing, expert advice, and other resources. In particular, business owners may be able to create and enhance their social capital by joining and participating in voluntary associations, thus making connections beyond their immediate circle of relationships. As Portes and Zhou (1996:228) concluded, " successful entrepreneurs are not isolated individuals. " In this paper, we examine the contribution that voluntary association membership and participation make to small business owners' access to critical organizational resources. Benefits from social capital created through organizational memberships may flow unevenly to men and women. Memberships may bring advantages to women participants, but the …
Rural financial markets in Tanzania:an analysis of access to financial services in Babati district, Manyara region

Tanzania is among the poorest countries in the world, with most of its population living in rural areas. Like most other developing countries, rural households’ access to financial services is very limited. The government has adopted series of economic reform measures since mid-1980s that include financial liberalization. Liberalization of the financial sector facilitated participation of private financial institutions, restructuring of public financial institutions and privatization, elimination of interest rate controls, credit allocation and targeting. In addition, the role of the Bank of Tanzania in supervision and regulation of financial institutions was strengthened. Following the privatization of the financial sector, the number of financial service providers increased and diversified, which include commercial banks, development banks, insurance and social security funds, and capital markets. The role of the central bank was re-defined and strengthened in terms of price stability, supervision and regulation. Although there is an increase in financial sector service providers and products, rural households’ access to financial services did not improve. To the contrary access to formal financial services is diminishing significantly, hence making poverty reduction initiatives more difficult.
Mourning 2.0—Continuing Bonds Between the Living and the Dead on Facebook

This study examines the burgeoning phenomenon of Facebook memorial pages and how this research about online social networking environments can contribute to the existing literature related to Klass, Silverman, and Nickman (1996) continuing bonds thesis. I argue that memorial pages constitute a new ritualized and public space for maintaining these continued bonds and that individuals exhibit several types of bonding interactions with the deceased. I conducted a content analysis on a purposively selected sample of 12 public Facebook “pages” where I coded 1,270 individual Wall postings. Analyses demonstrated that many individuals routinely used these Walls to continue their relationships with the deceased. Findings revealed several Wall posting categories, “guidance from beyond and reunion with the deceased,” “messages and visitations from the deceased,” and “conversations with the deceased,” which I then combined under a central thematic heading of “paranormal copresence. ” There were 267 Wall postings coded under “guidance and reunion,” 26 for “messages and visitations,” and 340 for “conversations,” with the total of 633 Wall postings under the central thematic heading of paranormal copresence. This research highlights how individuals have transcended the limitations of time and physical space in relation to traditional bereavement behavior and rituals and how data found on public websites, such as Facebook, can be used to further theorize bereavement and to demonstrate continue bonds between the living and the dead.
Cell Cycle Elongation Impairs Proliferation of Cerebellar Granule Cell Precursors in the Ts65Dn Mouse, an Animal Model for Down Syndrome

Mental retardation, the hallmark of Down syndrome (DS), has been attributed to the reduced number of neurons populating the DS brain. The Ts65Dn mouse model of DS displays several anomalies analogous to those in individuals with DS, including neurogenesis impairment. The goal of the current study was to determine whether cell cycle alterations underlie neurogenesis impairment in the cerebellum of the Ts65Dn mouse and to identify the molecular mechanisms responsible for this defect. In neonatal (2‐day old) Ts65Dn mice, cerebellar granule cell precursors exhibited a reduced proliferation rate (−40%) and a notable elongation (+45%) of the cell cycle. Alteration of cell cycle rate was due to elongation of the G2 and G1 phases. Microarray screening of cell cycle regulatory genes showed that Ts65Dn mice had a decreased expression of Cyclin B1 and Skp2, two key regulators of G2/M and G1/S transition. Results point at cell cycle elongation as major determinant of neurogenesis reduction in the cerebellum of Ts65Dn mice and suggest that this defect is specifically linked to an altered expression of two cell‐cycle regulatory genes, Cyclin B1 and Skp2. These findings may establish the basis for a therapeutic approach aimed at restoring neurogenesis in the DS brain.
Making the relationship mobile: an exploratory study of the impact of mobile marketing on the customer-brand relationship

The purpose of this thesis is to increase the understanding of how mobile marketing, in particular branded apps, impacts the customer-brand relationship. To gain a holistic comprehension of the phenomenon, the relationship is looked at from both the brand’s and the customer’s viewpoint. In order to fulfill the purpose, a qualitative approach was followed. The empirical data was analyzed through qualitative content analysis and grounded analysis respectively. This thesis it exploratory, thus laying the foundation for future research into the field of mobile marketing and branded apps. The empirical data was collected by employing two different methods. Firstly, the branded apps of the top 50 brands were analyzed. Secondly, two focus groups were carried out. It was found that mobile marketing has empowered the customer. In this process, the communication between customers and brands has turned into a two-way dialogue and permission based marketing, one-to-one marketing, customer engagement and brand advocacy have become the major communication tools employed for building meaningful customer-brand relationships.
Identification and Classification of Usage Patterns in Long-Term Activity Tracking

Activity trackers are frequently used in health and well-being, but their application in effective interventions is challenging. While research for reasons of use and non-use is ongoing, little is known about the way activity trackers are used in everyday life and over longer periods. We analyzed data of 104 individuals over 14,413 use days, and in total over 2.5 years. We describe general tracker use, periodic changes and overall changes over time, and identify characteristic patterns. While the use of trackers shows large individual heterogeneity, from our findings we could identify and classify general patterns for activity tracker use such as try-and-drop, slow-starter, experimenter, hop-on hop-off, intermittent and power user. Our findings contribute to the body of knowledge towards the successful design of effective health technologies, health interventions, and long-term health applications.
Do Industry Specialist Auditors Add Value in Mergers and Acquisitions

This study examines whether the stock market returns surrounding announcements of mergers and acquisitions (M&A) are higher for acquiring firms audited by industry specialists. External auditors are uniquely positioned to provide assurance on the financial statements of their acquiring clients both before and after an acquisition. Also, an important aspect of due diligence in M&A transactions is the external auditor’s review of the accounting records, financial statements, internal controls and information systems of the target company. Using a sample of 4,283 M&A announcements between 1988 and 2011 in the United States of America, we report the results from our main regressions, controlling for all the bidder traits and deal characteristics. We examine incremental effect of audit firm specialization on cumulative abnormal returns. We also measure the effect of audit firm industry specialization in a reduced sample of 3,946 acquisitions after removing all non-Big N auditors. We use Heckman’s (1979) two-step procedure to ensure that announcement period return to the size of the audit firm is not driven by the determinants related to auditor choice. Consistent with the idea that industry specialists provide higher quality assurance and possibly superior M&A advisory services, we find that the stock market returns are higher when acquiring firms are audited by industry specialists.
The estimate of the dispersion of the fast-fluctuating stationary Gaussian random process

In this study a new technique is presented for obtaining the single-channel estimate of the dispersion of the fast-fluctuating Gaussian random process with a free-form spectral density. This technique is the generalization of the discriminator-based method for the estimation of the signal parameter. It is established that the introduced estimate is the asymptotically unbiased and effective one. The facilities for its both analogue and digital hardware implementations are demonstrated.
A 6-month longitudinal study of early-onset tardive dyskinesia: association with olanzapine treatment and mild cognitive impairment in an elderly woman.

To the Editors: Tardive dyskinesia (TD) is a common and potentially irreversible hyperkinetic movement disorder resulting from long-term treatment with antipsychotic drugs that are antagonists at dopamine D2 receptors. Tardive dyskinesia is one of the most serious iatrogenic neurological complications of the first-generation antipsychotics. We present a case study of an elderly woman without a history of psychiatric disorders or previous typical antipsychotic use who developed TD after only 1 month exposure to olanzapine while on chronic treatment with galantamine. Notably, a cerebral magnetic resonance scan revealed cortical and subcortical multiple infarctions in chronic stage. During her hospitalization and 6 months prospective follow-up, several therapeutic approaches were introduced, but the patient did not exhibit remarkable and sustained improvement of her dyskinesia. We are aware of only limited previously reported cases of early-onset TD associated with olanzapine. We suggest that the risk for TD is not limited only to individuals with schizophrenia—it may also potentially develop in at-risk patient populations with ischemic brain lesions exposed to atypical antipsychotic drugs.
Pontine respiratory‐modulated activity before and after vagotomy in decerebrate cats

The dorsolateral (DL) pons modulates the respiratory pattern. With the prevention of lung inflation during central inspiratory phase (no‐inflation (no‐I or delayed‐I) tests), DL pontine neuronal activity increased the strength and consistency of its respiratory modulation, properties measured statistically by the η2 value. This increase could result from enhanced respiratory‐modulated drive arising from the medulla normally gated by vagal activity. We hypothesized that DL pontine activity during delayed‐I tests would be comparable to that following vagotomy. Ensemble recordings of neuronal activity were obtained before and after vagotomy and during delayed‐I tests in decerebrate, paralysed and ventilated cats. In general, changes in activity pattern during the delayed‐I tests were similar to those after vagotomy, with the exception of firing‐rate differences at the inspiratory–expiratory phase transition. Even activity that was respiratory‐modulated with the vagi intact became more modulated while withholding lung inflation and following vagotomy. Furthermore, we recorded activity that was excited by lung inflation as well as changes that persisted past the stimulus cycle. Computer simulations of a recurrent inhibitory neural network model account not only for enhanced respiratory modulation with vagotomy but also the varied activities observed with the vagi intact. We conclude that (a) DL pontine neurones receive both vagal‐dependent excitatory inputs and central respiratory drive; (b) even though changes in pontine activity are transient, they can persist after no‐I tests whether or not changes in the respiratory pattern occur in the subsequent cycles; and (c) models of respiratory control should depict a recurrent inhibitory circuitry, which can act to maintain the stability and provide plasticity to the respiratory pattern.