Miracle-dz/UniFAR-FTUs huggingface dataset:
Use of genetic testing and prophylactic mastectomy and oophorectomy in women with breast or ovarian cancer from families with a BRCA1 or BRCA2 mutation.

PURPOSE To analyze the use of genetic testing, prophylactic mastectomy, and oophorectomy among women with breast and/or ovarian cancer from families with a BRCA1 or BRCA2 mutation. PATIENTS AND METHODS We examined prospectively the use of BRCA1/BRCA2 testing in all women with a primary breast or ovarian cancer from a consecutive series of 112 high-risk families in which a BRCA1/BRCA2 mutation eventually was identified. The rate of prophylactic bilateral and contralateral mastectomy and prophylactic oophorectomy was analyzed in the women who carried a BRCA1/BRCA2 mutation and who had no metastatic disease at the time of the genetic test disclosure. We examined predictors for genetic test uptake and prophylactic surgery using univariate and multivariate analysis. RESULTS Overall, 192 of 220 women (87%) with primary tumors underwent genetic testing. Eleven of these 192 tested women (6%) appeared not to carry the family-specific BRCA1/BRCA2 mutation. Genetic testing occurred significantly more frequently at ages younger than 50 years (P =.04) and in persons with multiple primary tumors (P =.02). Among eligible women, 35 of 101 (35%) requested bilateral or contralateral mastectomy, and 47 of 95 (49%) requested oophorectomy. Women aged younger than 50 years and women who developed their first tumor after the initial identification of a BRCA1/BRCA2 mutation in the family were significantly (both P =.01) more likely to opt for prophylactic bilateral or contralateral mastectomy. CONCLUSION In a clinical setting, we show a high demand for BRCA1/BRCA2 testing and for prophylactic surgery by women with breast and/or ovarian cancer from high-risk families.
Mentors or Teachers? Microenterprise Training in Kenya

We use a randomized controlled trial to demonstrate that inexperienced female microenterprise owners in a Kenyan slum benefit from mentorship by an experienced entrepreneur in the same community. Mentorship increases profits by 20 percent on average with initially large effects that fade as matches dissolve. We conduct a formal business education intervention, which has no effect on profits despite changes in business practice. Our results demonstrate that missing information is a salient barrier to profitability, but the type of information matters: access to the localized, specific knowledge of mentors increases profit while abstract, general information from the class does not. (JEL D83, J16, L25, L26, O14, O15)
Nature and Consequences of the Systemic Inflammatory Response Induced by Lung Inflammation

Lung inflammation is the basis for the majority of acute and chronic lung conditions. Acute lung injury (ALI) caused by either communicable (such as infection) or non-communicable (such as acid aspiration) diseases are characterized by a rapidly induced inflammatory response in the lung. There are numerous causes for ALI, as the lung is exposed to external factors either via the airways (infectious agents and environmental pollutants) or via the blood stream (sepsis, endotoxin, fat) and, when severe, can lead to acute respiratory distress syndrome (ARDS), a spectrum of lung diseases characterized by a severe inflammatory process in the lung parenchyma causing diffuse alveolar damage and respiratory failure [1, 2]. This acute inflammatory response in the lung is strongly associated with a systemic inflammatory response that may lead to multiple organ dysfunction and is associated with high mortality [3]. Similarly, chronic inflammatory lung conditions such as chronic obstructive pulmonary disease (COPD), asthma, bronchiectasis and interstitial lung diseases, especially those associated with collagen vascular disease, have in recent years also been shown to be accom‐ panied by a systemic inflammatory response, albeit different in nature [4-14]. In addition, the systemic response induced by chronic lung inflammation is also associated with downstream adverse effects on different organ systems. This chapter will focus on defining the nature and features of this systemic response as a consequence of lung inflammation and will focus predominantly on chronic inflammatory lung conditions.
Direct and inverted DNA repeats associated with P‐glycoprotein gene amplification in drug resistant Leishmania.

The H circle of Leishmania species contains a 30 kb inverted duplication separated by two unique DNA segments, a and b. The corresponding H region of chromosomal DNA has only one copy of the duplicated DNA. We show here that the chromosomal segments a and b are flanked by inverted repeats (198 and 1241 bp) and we discuss how these repeats could lead to formation of H circles from chromosomal DNA. Selection of Leishmania tarentolae for methotrexate resistance indeed resulted in the de novo formation of circles with long inverted duplication, but two mutants selected for arsenite resistance contained new H region plasmids without such duplications. One of these plasmids appears due to a homologous recombination between two P‐glycoprotein genes with a high degree of sequence homology. Our results show how the same DNA region in Leishmania may be amplified to give plasmids with or without long inverted duplications and apparently by different mechanisms.
Herpes and cytomegalovirus esophagitis

A 46-year-old manwho underwent a liver transplant in 2001 for fulminant hepatitis of unknown etiology was diagnosed with a liver non-Hodgkin lymphoma (posttransplant lymphoproliferative disease) in 2011. Some months later, he developed an acute hepatocellular rejection that was treated with high doses of steroids. The patient was admitted because of fever and severe odynophagia that was hindering oral intake. He had multiple painful ulcers on his tongue, palate, and oral mucosa. Upper gastrointestinal endoscopy revealed large superficial, circumferential ulcers with well-defined margins and yellow exudate in the mid and upper esophagus (●" Fig.1). Biopsies taken from the ulcer base and borders confirmed herpes simplex virus (HSV) and cytomegalovirus (CMV) co-infection (●" Fig.2). Polymerase chain reaction (PCR) of the esophageal mucosa for HSV and CMV DNA was positive. Human immunodeficiency virus (HIV) serology was negative. The patient’s condition rapidly deteriorated and he died from sepsis and liver failure. Patients with HIV infection, those on chemotherapeutic agents or steroids, and transplant recipients have a high frequency of esophageal infections, although cases of multiple viral infections are very rare [1]. Long-term high-dose corticosteroids may predispose to HSV and CMV infection, although they are much less commonly diagnosed than Candida infections [2]. Esophageal ulcers due to CMV are typically large, shallow, solitary or multiple, and located in the mid or distal esophagus [3]. In HSV esophagitis, the morphology depends on the duration of infection [2] and includes nonspecific inflammation, discrete ulcers, coalescent ulcers, and pseudomembranous esophagitis in the mid or lower esophagus. Ulcers due to HSV are typically associated with a yellowish exudate [4]. Three or more biopsies are generally required to rule out viral esophagitis [5]. Co-infection with HSV and CMV has a higher incidence of complications, namely perforation and bleeding [1].
Experience of an Orthoplastic Limb Salvage Team after the Haiti Earthquake: Analysis of Caseload and Early Outcomes

Background: After the devastating earthquake in Haiti on January 12, 2010, a British orthoplastic limb salvage team was mobilized. The team operated in a suburb of Port-au-Prince from January 20, 2010. This analysis gives an overview of the caseload and early outcomes. Methods: A retrospective analysis of operative data from the log book was performed from the opening of the facility on January 20, 2010, until March 12, 2010. Results: In total, 348 operations were carried out on 158 patients, at an average of 47 cases per week. Seventy-three percent of the cases were soft-tissue cases and 25 percent were bony or combined soft-tissue and bony cases. The majority of bony procedures (n = 26; 16 percent) and flap procedures (n = 16; 10 percent) took place in the early weeks (weeks 1 through 4). Combined orthoplastic cases accounted for 37 percent of cases (16 of 44) in week 2 but only 7 percent (three of 43) in week 7. General anesthetic cases accounted for 89 percent of cases (39 of 44) in week 2 but only 40 percent (17 of 43) in week 7. Only six patients (4 percent) underwent amputation, but 36 operations (10 percent) dealt with the sequelae of amputation. Sixteen patients (10 percent) suffered complications, including two amputations for failed limb salvage. Conclusions: This article reports the outcomes of a limb salvage team in the acute response after an earthquake disaster with a favorable amputation rate and highlights the potential benefit of mobilizing this type of team. Detailing the changing caseload over time will allow for more efficient planning in case of a similar future disaster.
Has the time come to use antioxidant therapy in uraemic patients?

Oxidative stress and inflammation currently resound throughout the scientific community as risk factors for arteriosclerosis and cardiovascular diseases. Already more or less reasonable recommendations appear in various lay-media, providing suggestions of how to prevent arteriosclerosis by antioxidative strategies, including, for example, daily consumption of red wine containing antioxidative tannins, or daily administration of vitamin E. What currently is the evidence for antioxidative treatment? Are there any validated recommendations particularly for uraemic patients bearing a high risk for arteriosclerosis and cardiovascular diseases? These questions will be addressed in the following.
Single-Stage, Universal-Input AC/DC LED Driver With Current-Controlled Variable PFC Boost Inductor

This paper presents a single-stage flyback power-factor-correction (PFC) circuit with a variable boost inductance for high-brightness LED applications for the universal input voltage (90-270 Vrms). The proposed circuit overcomes the limitations of the conventional single-stage PFC flyback with a constant boost inductance that cannot be designed to achieve a practical maximum bulk-capacitor voltage level (i.e., less than 450 V) at high line while meeting required line-current harmonic specifications at low line. According to the proposed method for achieving variable boost inductance, the boost inductance has a constant high value at high line, while at low line it is reduced proportionally to the load current, so that the IEC 61000-3-2 class C and corresponding Japanese JIS C 61000-3-2 class C line-current harmonic limits are satisfied. The proposed single-stage PFC flyback LED driver with the variable boost inductor is experimentally verified on a 24-V/91-W prototype circuit.
Pathophysiology of massive infantile spasms: Perpective on the putative role of the brain adrenal axis

Massive infantile spasms are an age‐specific seizure syndrome of infancy. Uniquely, the spasms respond to hormonal manipulation using adrenocorticotropic hormone(ACTH) or glucocorticoids. A hypothesis explaining the efficacy of hormonal therapy, age ‐specificity, multiple causative factors, and spontaneous resolution of infantile spasms is presented. Corticotropin‐releasing hormone(CRH), an excitant neuropeptide supressed by ACTH/Steroids, is implicated. Evidence for the age‐specific vonvulsant properties of CRH is presented, and a putative secenario in which a stressinduced enhancement of endogenous CRH‐mediated seizures is discussed. Clinical resting of the CRH‐Excess theory and its therapeutic implication are suggested.
Separate SCFCDC4 recognition elements target Cdc6 for proteolysis in S phase and mitosis

The Cdc6 DNA replication initiation factor is targeted for ubiquitin‐mediated proteolysis by the E3 ubiquitin ligase SCFCDC4 from the end of G1 phase until mitosis in the budding yeast Saccharomyces cerevisiae. Here we describe a dominant‐negative CDC6 mutant that, when overexpressed, arrests the cell cycle by inhibiting cyclin‐dependent kinases (CDKs) and, thus, prevents passage through mitosis. This mutant protein inhibits CDKs more efficiently than wild‐type Cdc6, in part because it is completely refractory to SCFCDC4‐mediated proteolysis late in the cell cycle and consequently accumulates to high levels. The mutation responsible for this phenotype destroys a putative CDK phosphorylation site near the middle of the Cdc6 primary amino acid sequence. We show that this site lies within a novel Cdc4‐interacting domain distinct from a Cdc4‐interacting site identified previously near the N‐terminus of the protein. We show that both sites can target Cdc6 for proteolysis in late G1/early S phase whilst only the newly identified site can target Cdc6 for proteolysis during mitosis.
Distribution of Norepinephrine in the Failing Bovine Heart: Correlation of Chemical Analysis and Fluorescence Microscopy

Studies were carried out during experimental heart failure induced in calves to compare the depletion of cardiac norepinephrine in the failing heart to the histochemical appearance of the adrenergic innervation in this tissue. A correlation has been established between the reduction of norepinephrine concentration and the changes in the distribution of the adrenergic neurotransmitter in the tissues. Absence of fluorescence in terminal varicose fibers in close association with cardiac muscle cells was characteristic of the failing heart. Little or no change occurred in preterminal fibers or in terminal fibers in connective tissue septa or around blood vessels. In two steers, recovery from heart failure was shown to be associated with a virtual restoration of the norepinephrine concentration and of thehistochemical appearance of the adrenergic nerve distribution in 28 days or less. These findings suggest that a reversible abnormality, possibly of neurotransmitter storage or synthesis, or both, is induced in the terminal portion of the cardiac adrenergic innervation as the result of the development of the failure state.
Structure of a Novel P-superfamily Spasmodic Conotoxin Reveals an Inhibitory Cystine Knot Motif* 210

Conotoxin gm9a, a putative 27-residue polypeptide encoded by Conus gloriamaris, was recently identified as a homologue of the “spasmodic peptide”, tx9a, isolated from the venom of the mollusk-hunting cone shellConus textile (Lirazan, M. B., Hooper, D., Corpuz, G. P., Ramilo, C. A., Bandyopadhyay, P., Cruz, L. J., and Olivera, B. M. (2000) Biochemistry 39, 1583–1588). The C. gloriamaris spasmodic peptide has been synthesized, and the refolded polypeptide was shown to be biologically active using a mouse bioassay. The chemically synthesized gm9a elicited the same symptomatology described previously for natively folded tx9a, and gm9a and tx9a were of similar potency, implying that neither the two γ-carboxyglutamate (Gla) residues found in tx9a (Ser8and Ala13 in gm9a) nor Gly1 (Ser1in gm9a) are crucial for biological activity. We have determined the three-dimensional structure of gm9a in aqueous solution and demonstrated that the molecule adopts the well known inhibitory cystine knot motif constrained by three disulfide bonds involving Cys2-Cys16, Cys6-Cys18and Cys12-Cys23. Based on the gm9a structure, the sites of Gla substitution in tx9a are in loops located on one surface of the molecule, which is unlikely to be involved directly in receptor binding. Because this is the first structure reported for a member of the newly defined P-superfamily conotoxins, a comparison has been made with structurally related conotoxins. This shows that the structural scaffold that characterizes the P-conotoxins has the greatest potential for exhibiting structural diversity among the robust inhibitory cystine knot-containing conotoxins, a finding that has implications for functional epitope mimicry and protein engineering.
How Much Do Official Price Indexes Tell Us About Inflation

Official price indexes, such as the CPI, are imperfect indicators of inflation calculated using ad hoc price formulae different from the theoretically well-founded inflation indexes favored by economists. This paper provides the first estimate of how accurately the CPI informs us about "true" inflation. We use the largest price and quantity dataset ever employed in economics to build a TA¶rnqvist inflation index for Japan between 1989 and 2010. Our comparison of this true inflation index with the CPI indicates that the CPI bias is not constant but depends on the level of inflation. We show the informativeness of the CPI rises with inflation. When measured inflation is low (less than 2.4% per year) the CPI is a poor predictor of true inflation even over 12-month periods. Outside this range, the CPI is a much better measure of inflation. We find that the U.S. PCE Deflator methodology is superior to the Japanese CPI methodology but still exhibits substantial measurement error and biases rendering it a problematic predictor of inflation in low inflation regimes as well.
Calcineurin inhibitors for the treatment of atopic dermatitis

Background: Atopic dermatitis (AD) is a chronic disease characterized by periods of remission and relapse. Therapeutic objectives for AD should be to quickly reduce disease symptoms by targeting pathophysiological pathways, and to provide long-term management by reducing recurrences. Objective: Calcineurin inhibitors currently appear to be one of the most promising alternative systemic and topical compounds to treat AD. This review focuses on new developments of topical calcineurin inhibitors, therapeutic regimens including long-term management, and prophylaxis of AD. Methods: The published clinical studies that present data on treatment of AD with calcineurin inhibitors were assessed. Results/conclusion: Topical calcineurin inhibitors such as tacrolimus and pimecrolimus provide an effective treatment for AD. They are useful for long-term management and prophylaxis of AD. Safety concerns with regard to increased risk for lymphomas or skin cancer could not be confirmed but will remain under careful observation.
Group M-based HIV-1 Gag peptides are frequently targeted by T cells in chronically infected US and Zambian patients

Background:The enormous sequence diversity of HIV-1 has been a major obstacle in the development of a globally useful vaccine for AIDS. The consensus and ancestral sequence-based immunogens minimize the genetic distance between contemporary isolates and vaccine strains. Hence these sequences may be promising candidates for HIV vaccines or serve as a universal reagent set for evaluating Gag-specific responses. Methods:In this study, we measured the T-cell reactivity to consensus (subtype A, B, C and group M), ancestral (group M and subtype B) and HXB2 Gag peptides (15-mers overlapping by 11) in HIV-1-infected subjects from two reference populations. We evaluated the Gag-specific T-cell responses in 43 chronically infected US (subtype B) and 13 Zambian (subtype C) subjects using an interferon-γ enzyme-linked immunosorbent spot assay. Results:Our findings demonstrate a broad cross-reactivity of nearly 70% among all the seven Gag immunogens evaluated. Consensus M sequences elicited similar levels of responses as did the consensus B, ancestral subtype B and HXB2 peptides in subtype B-infected US patients. In subtype C-infected Zambian subjects, responses of similar breadth and magnitude were elicited by consensus C, consensus M and ancestral M peptides. Conclusion:Our data demonstrate that peptide pools based on consensus or ancestral M-based sequences can be used to evaluate Gag-specific responses elicited by subtype B or subtype C-based immunogens.
Impact of perceived security on consumer trust in online banking

Consumer trust has been recognised as a critical component of the electronic banking industry. Factors that affect trust and its development vary from traditional banking services because of the uncertain nature of the online environment. Extensive efforts in identifying factors that affect trust have shown security to play an important role in its development. Every step in the online banking activities of users are secured by one of more security mechanisms. Analysing the role of these mechanisms in developing a user’s perception of security and the impact of this perception on trust provides a pathway to study the role of security in trust development. The objective in this study is to identify the relationship that exists between trust and security. On analysing prior research, the components of trust and security are identified and these form the basis in defining the nature of the relationship between the two constructs. A model of this relationship is hypothesised based on the theory and empirical results obtained by researchers. This model shows that security for a user exists as a perception and this perception is positively affected by the presence of different security mechanisms. The dimension of trust that is affected by security is institution based trust. Increase in the perception of security is shown to play a positive role in developing this component of trust. These relationships define the connection between trust and security in the e-banking industry. A survey conducted at the AUT campus provided both reliable and valid data that could further be analysed using confirmatory factor analysis. The results of this analysis show that there is a significant impact of security mechanisms on a user’s perception of security Privacy, authentication, authorization and availability mechanisms are found to contribute the most to the development of their individual perception components and in turn the overall perception of security. This indicated that awareness levels in users regarding security mechanisms of banking websites are high. Thus, these mechanisms play an important and significant role in developing perception of security.
The Determinants of the Capital Structure: Evidence from Jordanian Industrial Companies

This study examined the capital structure of listed industrial companies on Amman Stock Exchange (ASE) over the period (2001-2005). The findings of this study contribute towards a better understanding of financing behaviour in Jordanian industrial companies. Hypotheses, based on comparing the relationships between Leverage ratio (Lev 1), LTD/TD (Long-term debts/total debts) and five explanatory variables that represent size, tangibility, profitability, long-term debt and short-term debt. To test those relationships regression analysis for Leverage ratio (Lev 1) and model was used to explain determinants of the capital structure of Jordanian industrial companies on the time period (2001 - 2005). There was a significant positive relationship between leverage ratio (Lev 1) and size (TA), Tangibility (Tang), long-term debt (LTD) and short-term debt (STD) and there was a significant negative relationship between leverage ratio and Profitability of the firm. In other words, the results of this study showed that a significant positive relationship between LTD/TD and size (TA), Tangibility (Tang), and long-term debt (LTD) and there was a negative relationship between LTD/TD and short-term debt of the firm. Also, the results showed that Total assets, Tangibility, Long-term debt, had a positive correlation with LTD/TD. While, short-term debt had a negative correlation with LTD/TD. As well as, Jordanian industrial companies are depending on equity for financing their investments, where, the equity of Jordanian industrial companies represents about (70%) from their total finance. Despite the fact that this correlation matrix ignores joint effects of more than one variable on leverage, the Long-term debt, and Short-term debt are positively related to Tangibility and Total assets. Profitability has a negative correlation with short-term debt and total debt ratios. This implies that (1) Growing companies and companies with high levels of tangible assets tend to use short-term debt rather than long-term debt. (2) Large and profitable companies are less likely to use short-term debt and tend to use less debt overall.