Miracle-dz/UniFAR-FTUs huggingface dataset:
Shock performance study of solder joints in wafer level packages

In this paper, an integrated testing, finite element modeling and failure analysis approach for drop test reliability of wafer level packages is developed to examine the shock performance of large array wafer level packages. For standard JEDEC drop test, it has been found that corner component group (group A) failed first for 12×12 array packages. This is different from previously reported failure test data of BGA packages. Careful analysis concluded that the high failure rate of group A is mainly due to the effect of mounting screws rather than the intrinsic strength of the package. For a given WLP, corner balls always fail first during drop test. The crack initiates at inner side of the solder joint and propagate towards the opposite side. The primary failure is always on the intermetallic compound (IMC) at WLP side. It has been found that drop reliability significantly decreases with array size increasing. Novel finite element modeling approach has been developed to correlate with experimental data. The finite element model was validated with experimental board strain data, and frequency analysis. In-plane principal strain at corner locations and maximum peeling stress in IMC at critical solder joints are used to correlate with experimental data. Excellent agreement was reached to predict the failure rate of components in each group. Two new findings have been observed and validated. One is that existing JEDEC board design will lead group A components fail first for certain array size of wafer level packages. Another finding is that PCB board strain does not always correlate with maximum peeling stress in solder joints when array size changes.
Interactive Unawareness

The standard state-spaces of asymmetric information preclude non-trivial forms of unawareness (Modica and Rustichini, 1994, Dekel, Lipman and Rustichini, 1998). We introduce a generalized state-space model that allows for non-trivial unawareness among several individuals, and which satisfies strong properties of knowledge as well as all the desiderata on unawareness proposed this far in the literature.
School professionals' perceptions about the impact of chronic illness in the classroom.

BACKGROUND Children with chronic health conditions spend most of their day in the school system. The complexity of illness management and disease sequela can alter their school experience. However, little is known about what educators are concerned about if these children are in their classroom. OBJECTIVE To assess educators' perceptions of the impact of having children with different chronic health conditions in the classroom. METHODS Teachers and other school professionals in 23 elementary schools were surveyed about the impact of having a child with each of 6 chronic health conditions--AIDS, asthma, congenital heart disease, diabetes mellitus, epilepsy, and leukemia--in the classroom. They responded to 13 statements about the potential academic impact on the child, impact on peers, personal risk or liability, and additional time or attention demands for the teacher. Total scores were determined for the degree of perceived impact for each issue and chronic health condition and the proportion of teachers with negative perceptions for different issues. RESULTS The mean total scores (2.4 of 5) showed overall a positive perception by school professionals about children with chronic conditions in the classroom. Acquired immunodeficiency syndrome and epilepsy were perceived to have the most impact and asthma the least impact. The 2 educator issues (time or extra attention and personal risk or liability) were of the most concern to educators. Fifty-three percent were concerned about an emergency occurring with the child in the classroom and 27% were concerned about legal liability. Educator concerns of the risk of classroom emergencies or death were disproportionate to the clinical risk of the conditions especially for epilepsy and congenital heart disease. CONCLUSIONS Overall school professionals have positive attitudes about children with chronic health conditions in the classroom, but concerns about specific diseases and issues exist. If parents provide most of the disease information, some of the educators' concerns voiced in this study may not be addressed. Health care professionals can help by providing educators with appropriate information about the risk and functional impact of childhood chronic health conditions.
Dissecting karyotypic patterns in malignant melanomas: Temporal clustering of losses and gains in melanoma karyotypic evolution

Malignant melanomas can be divided into two major subtypes, involving either the skin or eye melanomas. Both tumor forms exhibit highly complex karyotypes with nonrandom recurrent chromosomal imbalances. Loss of chromosome 3, the short arm of chromosome 1, and gain of 8q have been suggested to be associated with eye melanomas, whereas gain of 6p and loss of 6q have been more often seen in skin melanomas. Imbalances implicated in tumor progression include among others, −10 and +7. In spite of the abundance of cytogenetic information, with more than 300 published karyotypes, very little is known about the mode of karyotypic evolution or of the presence of possible cytogenetic pathways. In our investigation, we have used 362 melanoma karyotypes, including both the skin and eye subtypes, to identify the most frequently occurring imbalances. Tumor cases were then classified with respect to the presence or absence of these imbalances and statistically analyzed in order to assess the order of appearance of chromosomal imbalances, the presence of karyotypic pathways, as well as possible cytogenetic subtypes. We show that the melanomas develop through one mode of karyotypic evolution, common to both low and high complexity karyotypes, and we establish the temporal order by which the different imbalances occur. By applying several statistical methods, we show that at least two cytogenetic pathways of clonal evolution exist in malignant melanomas, one initiated with −3 and one with +6p, and that these pathways operate in both skin and eye melanomas. © 2003 Wiley‐Liss, Inc.
Characterization of a Shiga Toxin-Encoding Temperate Bacteriophage of Shigella sonnei

ABSTRACT A Shiga toxin (Stx)-encoding temperate bacteriophage ofShigella sonnei strain CB7888 was investigated for its morphology, DNA similarity, host range, and lysogenization inShigella and Escherichia coli strains. Phage 7888 formed plaques on a broad spectrum of Shigella strains belonging to different species and serotypes, including Stx-producingShigella dysenteriae type 1. With E. coli, only strains with rough lipopolysaccharide were sensitive to this phage. The phage integrated into the genome of nontoxigenic S. sonneiand laboratory E. coli K-12 strains, which became Stx positive upon lysogenization. Moreover, phage 7888 is capable of transducing chromosomal genes in E. coli K-12. The relationships of phage 7888 with the E. coli Stx1-producing phage H-19B and the E. coli Stx2-producing phage 933W were investigated by DNA cross-hybridization of phage genomes and by nucleotide sequencing of an 8,053-bp DNA region of the phage 7888 genome flanking the stx genes. By these methods, a high similarity was found between phages 7888 and 933W. Much less similarity was found between phages H-19B and 7888. As in the other Stx phages, a regulatory region involved in Q-dependent expression is found upstream of stxA and stxB (stx gene) in phage 7888. The morphology of phage 7888 was similar to that of phage 933W, which shows a hexagonal head and a short tail. Our findings demonstrate that stx genes are naturally transferable and are expressed in strains of S. sonnei, which points to the continuous evolution of human-pathogenic Shigella by horizontal gene transfer.
Cryptosporidium parvum infection of human intestinal epithelial cells induces the polarized secretion of C-X-C chemokines

Cryptosporidium parvum infects intestinal epithelial cells and does not invade deeper layers of the intestinal mucosa. Nonetheless, an inflammatory cell infiltrate that consists of neutrophils and mononuclear cells is often present in the lamina propria, which underlies the epithelium. This study investigated the host epithelial cell response to C. parvum by assessing in vitro and in vivo the expression and production of proinflammatory cytokines by intestinal epithelial cells after infection. The human colon epithelial cell lines HCT-8 and Caco-2 and human intestinal xenografts in SCID mice were infected with C. parvum. The expression and secretion of the C-X-C chemokines interleukin-8 (IL-8) and GROalpha were determined by reverse transcription-PCR analysis and enzyme-linked immunosorbent assay. Our results demonstrate that upregulated expression and secretion of IL-8 and GROalpha after C. parvum infection of intestinal epithelial cells first occurred 16 to 24 h after infection and increased over the ensuing 1 to 2 days. The kinetics of C-X-C chemokine production by C. parvum-infected epithelial cells contrast markedly with the rapid but transient expression of C-X-C chemokines by epithelial cells infected with invasive enteric bacteria. C-X-C chemokine secretion in C. parvum-infected epithelial cells occurred predominantly from the basolateral surface in polarized monolayers of Caco-2 cells grown in Transwell cultures, whereas cell lysis occurred at the apical surface. The basolateral secretion of IL-8 and GROalpha from C. parvum-infected epithelial cells suggests that C-X-C chemokines produced by those cells contribute to the mucosal inflammatory cell infiltrate in the underlying intestinal mucosa.
Preoperative automated fibre quantification predicts postoperative seizure outcome in temporal lobe epilepsy

Approximately one in every two patients with pharmacoresistant temporal lobe epilepsy will not be rendered completely seizure-free after temporal lobe surgery. The reasons for this are unknown and are likely to be multifactorial. Quantitative volumetric magnetic resonance imaging techniques have provided limited insight into the causes of persistent postoperative seizures in patients with temporal lobe epilepsy. The relationship between postoperative outcome and preoperative pathology of white matter tracts, which constitute crucial components of epileptogenic networks, is unknown. We investigated regional tissue characteristics of preoperative temporal lobe white matter tracts known to be important in the generation and propagation of temporal lobe seizures in temporal lobe epilepsy, using diffusion tensor imaging and automated fibre quantification. We studied 43 patients with mesial temporal lobe epilepsy associated with hippocampal sclerosis and 44 healthy controls. Patients underwent preoperative imaging, amygdalohippocampectomy and postoperative assessment using the International League Against Epilepsy seizure outcome scale. From preoperative imaging, the fimbria-fornix, parahippocampal white matter bundle and uncinate fasciculus were reconstructed, and scalar diffusion metrics were calculated along the length of each tract. Altogether, 51.2% of patients were rendered completely seizure-free and 48.8% continued to experience postoperative seizure symptoms. Relative to controls, both patient groups exhibited strong and significant diffusion abnormalities along the length of the uncinate bilaterally, the ipsilateral parahippocampal white matter bundle, and the ipsilateral fimbria-fornix in regions located within the medial temporal lobe. However, only patients with persistent postoperative seizures showed evidence of significant pathology of tract sections located in the ipsilateral dorsal fornix and in the contralateral parahippocampal white matter bundle. Using receiver operating characteristic curves, diffusion characteristics of these regions could classify individual patients according to outcome with 84% sensitivity and 89% specificity. Pathological changes in the dorsal fornix were beyond the margins of resection, and contralateral parahippocampal changes may suggest a bitemporal disorder in some patients. Furthermore, diffusion characteristics of the ipsilateral uncinate could classify patients from controls with a sensitivity of 98%; importantly, by co-registering the preoperative fibre maps to postoperative surgical lacuna maps, we observed that the extent of uncinate resection was significantly greater in patients who were rendered seizure-free, suggesting that a smaller resection of the uncinate may represent insufficient disconnection of an anterior temporal epileptogenic network. These results may have the potential to be developed into imaging prognostic markers of postoperative outcome and provide new insights for why some patients with temporal lobe epilepsy continue to experience postoperative seizures.
Phase II study of dasatinib in patients with advanced non-small-cell lung cancer.

PURPOSE Src family kinases (SFKs) promote cancer progression and are commonly expressed in non-small-cell lung cancer (NSCLC), but the clinical effects of SFK inhibition in NSCLC are unknown. We conducted a phase II trial of the SFK inhibitor dasatinib for advanced NSCLC. We tested the hypotheses that the activation of epidermal growth factor receptor (EGFR) or SFK or modulation of serum cytokines may predict a response to dasatinib. PATIENTS AND METHODS Patients received dasatinib as first-line therapy. Response was measured by tumor size on computed tomography scans and by metabolic activity on positron emission tomography scans. Tissue samples taken before patients received dasatinib were tested for EGFR and Kras mutation and phosphorylated SFK expression. RESULTS Thirty-four patients were enrolled. The overall disease control rate (partial responses plus stable disease) for dasatinib was 43%. One patient had a partial response to therapy. Eleven patients (32%) had a metabolic response to dasatinib. SFK activation and EGFR and Kras mutations in tumor tissue did not predict response to dasatinib. Significant toxicities included fatigue and dyspnea. The presence of a pleural effusion before dasatanib therapy predicted the development of a clinically significant effusion during therapy. CONCLUSION Dasatinib as a single agent had modest clinical activity that was lower than that generally observed in patients with NSCLC who receive chemotherapy. Pleural effusion was an expected and problematic toxicity that was successfully treated with steroids, diuretics, and dose interruptions. Marked activity in one patient and prolonged stable disease in four others suggested a potential subpopulation of patients with dasatinib-sensitive NSCLC.
Fetoscopic single-layer repair of open spina bifida using a cellulose patch: preliminary clinical experience

Abstract Objective: To report our preliminary clinical experience in the antenatal correction of open spina bifida (OSB) using a fetoscopic approach and a simplified closure technique. Methods: Four fetuses with lumbar-sacral defects were operated in utero from 25 to 27 weeks. Surgeries were performed percutaneously under general anesthesia using three trocars and partial carbon dioxide insufflation. After dissection of the neural placode, the surrounding skin was closed over a cellulose patch using a single continuous stitch. Results: Surgical closure was successful in three of the four cases. All successful cases showed improvement of the hindbrain herniation and no neonatal neurosurgical repair was required in two cases. Delivery occurred between 31 and 33 weeks, and no fetal or neonatal deaths occurred. Ventriculoperitoneal shunting was not needed in two out of the 3 successful cases. Conclusions: Our preliminary experience suggests that definitive fetoscopic repair of OSB is feasible using our innovative surgical technique. A phase I trial for the fetoscopic correction of OSB with this technique is currently being conducted.
Seven-year trends in HIV-1 infection rates, and changes in sexual behaviour, among adults in rural Uganda

ObjectiveTo assess trends in HIV-1 infection rates and changes in sexual behaviour over 7 years in rural Uganda. MethodsAn adult cohort followed through eight medical–serological annual surveys since 1989–1990. All consenting participants gave a blood sample and were interviewed on sexual behaviour. ResultsOn average, 65% of residents gave a blood sample at each round. Overall HIV-1 prevalence declined from 8.2% at round 1 to 6.9% at round 8 (P = 0.008). Decline was most evident among men aged 20–24 years (11.7 to 3.6%;P < 0.001) and women aged 13–19 (4.4% to 1.4%;P = 0.003) and 20–24 (20.9% to 13.8%;P = 0.003). However, prevalence increased significantly among women aged 25–34 (13.1% to 16.6%;P = 0.04). Although overall incidence declined from 7.7/1000 person-years (PY) in 1990 to 4.6/1000 PY in 1996, neither this nor the age-sex specific rates changed significantly (P > 0.2). Age-standardized death rates for HIV-negative individuals were 6.5/1000 PY in 1990 and 8.2/1000 PY in 1996; corresponding rates for HIV-positive individuals were 129.7 and 102.7/1000 PY, respectively. There were no significant trends in age-adjusted death rates during follow-up for either group. There was evidence of behaviour change towards increase in condom use in males and females, marriage at later age for girls, later sexual debut for boys and a fall in fertility especially among unmarried teenagers. ConclusionsThis is the first general population cohort study showing overall long-term significant reduction in HIV prevalence and parallel evidence of sexual behaviour change. There are however no significant reductions in either HIV incidence or mortality.
Socioeconomic Inequalities in Quality of Care and Outcomes Among Patients With Acute Coronary Syndrome in the Modern Era of Drug Eluting Stents

Background The rapidly changing landscape of percutaneous coronary intervention provides a unique model for examining disparities over time. Previous studies have not examined socioeconomic inequalities in the current era of drug eluting stents (DES). Methods and Results We analyzed 835 070 hospitalizations for acute coronary syndrome (ACS) from the Healthcare Cost and Utilization Project across all insurance types from 2008 to 2011, examining whether quality of care and outcomes for patients with ACS differed by income (based on zip code of residence) with adjustment for patient characteristics and clustering by hospital. We found that lower‐income patients were less likely to receive an angiogram within 24 hours of a ST elevation myocardial infarction (STEMI) (69.5% for IQ1 versus 73.7% for IQ4, P<0.0001, OR 0.79 [0.68 to 0.91]) or within 48 hours of a Non‐STEMI (47.6% for IQ1 versus 51.8% for IQ4, P<0.0001, OR 0.86 [0.75 to 0.99]). Lower income was associated with less use of a DES (64.7% for IQ1 versus 71.2% for IQ4, P<0.0001, OR 0.83 [0.74 to 0.93]). However, no differences were found for coronary artery bypass surgery. Among STEMI patients, lower‐income patients also had slightly increased adjusted mortality rates (10.8% for IQ1 versus 9.4% for IQ4, P<0.0001, OR 1.17 [1.11 to 1.25]). After further adjusting for time to reperfusion among STEMI patients, mortality differences across income groups decreased. Conclusions For the most well accepted procedural treatments for ACS, income inequalities have faded. However, such inequalities have persisted for DES use, a relatively expensive and until recently, controversial revascularization procedure. Differences in mortality are significantly associated with differences in time to primary PCI, suggesting an important target for understanding why these inequalities persist.
Casopitant: In Vitro Data and SimCyp Simulation to Predict In Vivo Metabolic Interactions Involving Cytochrome P450 3A4

Casopitant [1-piperidinecarboxamide,4-(4-acetyl-1-piperazinyl)-N-((1R)-1-(3,5-bis(trifluoromethyl)phenyl)-ethyl)-2-(4-fluoro-2-methylphenyl)-N-methyl-(2R,4S), GW679769] has previously been shown to be a potent and selective antagonist of the human neurokinin-1 receptor, the primary receptor of substance P, both in vitro and in vivo, with good brain penetration properties. On the basis of this mode of action it was evaluated for the prevention of chemotherapy-induced and postoperative nausea and vomiting, and for the chronic treatment of anxiety, depression, insomnia, and overactive bladder. Casopitant is shown to be a substrate, an inhibitor, and an inducer of CYP3A4, and, because of this complex behavior, it was difficult to identify the primary mechanism by which it may give rise to drug-drug interactions (DDIs) of clinical relevance. Moreover, the major circulating metabolite is itself an inhibitor of CYP3A4 in vitro. On the basis of the different clinical indications and the various potential comedications of casopitant, a relevant part of the clinical development plan was focused on the assessment of the importance of clinical DDIs. The present study provides an overview of the DDI potential profile of casopitant, based on in vitro data and clinical evidence of its interaction with CYP3A4 probe substrates midazolam and nifedipine, the strong inhibitor ketoconazole, and the inducer rifampin. Overall, the clinical data confirm the ability of casopitant to interact with CYP3A4 substrates, inhibitors, or inducers. The in vitro data are accurate and robust enough to build a reliable SimCyp population-based model to estimate the potential DDIs of casopitant and to minimize the clinical studies recommended.
Prospective Study of Pathogen Burden and Risk of Myocardial Infarction or Death

Background—We previously demonstrated that the risk of coronary artery disease (CAD) increased in relation to the number of pathogens (the “pathogen burden”) in a cross-sectional study. In the present prospective study with a different patient cohort, we evaluated the effect of pathogen burden on the risk of myocardial infarction (MI) or death among CAD patients. Methods and Results—IgG antibodies to cytomegalovirus (CMV), hepatitis A virus (HAV), herpes simplex virus type 1 (HSV1), HSV type 2 (HSV2), Chlamydia pneumoniae and Helicobacter pylori, and C-reactive protein (CRP) levels were tested in baseline blood samples from 890 patients who had significant CAD on angiography. The mean follow-up period was 3 years. The baseline prevalence of antibodies directed against CMV, HAV, HSV1, or HSV2, but not C pneumoniae and H pylori, was significantly higher among patients who subsequently developed MI or death than among control subjects. After adjustment for traditional risk factors, number of diseased vessels, and clinical presentation, relative hazards (95% confidence limits) for MI or death were 2.0 (1.4 to 3.2) for CMV, 1.6 (1.1 to 2.3) for HAV, and 1.5 (1.0 to 2.2) for HSV2. Increasing pathogen burden was significantly associated with increasing risk of MI or death in a dose-response fashion. Adjusted relative hazards of MI or death associated with pathogen burden were significant among individuals with low or high CRP levels. Conclusions—The results suggest that infection plays an important role in incident MI or death and that the risk posed by infection is independently related to the pathogen burden.