Mirage Andreev Spectra Generated by Mesoscopic Leads in Nanowire Quantum Dots.

We study transport mediated by Andreev bound states formed in InSb nanowire quantum dots. Two kinds of superconducting source and drain contacts are used: epitaxial Al/InSb devices exhibit a doubling of tunneling resonances, while, in NbTiN/InSb devices, Andreev spectra of the dot appear to be replicated multiple times at increasing source-drain bias voltages. In both devices, a mirage of a crowded spectrum is created. To describe the observations a model is developed that combines the effects of a soft induced gap and of additional Andreev bound states both in the quantum dot and in the finite regions of the nanowire adjacent to the quantum dot. Understanding of Andreev spectroscopy is important for the correct interpretation of Majorana experiments done on the same structures.

Additional chromosomal abnormalities in core-binding factor acute myeloid leukemia.

Despite sharing a similar genetic abnormality, patients with core binding factor acute myeloid leukemia (CBF-AML), which is characterized by the presence of t(8;21) or inv(16)/t(16;16), show heterogeneous survival. Other molecular or cytogenetic factors are supposed to have an impact on the prognosis. We enrolled 24 CBF-AML patients to determine the impact of cytogenetic abnormality, and c-KIT, FLT3, NPM1, and CEBPA mutations on the prognosis. Only three patients had the c-KIT mutation (3/24, 12.5%) and one had the FLT3 mutation. However, over half of the patients (14/24) harbored additional cytogenetic changes, including ten with loss of sexual chromosomes (LOS) [all in the t(8;21) group], and six had additional abnormalities (two cases had both LOS and additional abnormalities). From this small-number study, no association was found between c-KIT mutation and survival and relapse rate. However, additional chromosome abnormalities had a significant association with relapse of the disease (P = 0.027). Stem cell transplant had a trend of benefitting patients after relapse (P = 0.065). This implies that chromosome abnormalities occur in CBF-AML and might take part in the heterogeneous nature of CBF-AML.

Clinical and molecular characteristics of bloodstream infections caused by Candida albicans in children from 2003 to 2011.

We investigated the clinical and molecular characteristics of Candida albicans bloodstream infection (BSI) in children from a tertiary-level medical centre in Taiwan over a 9-year period from January 2003 to December 2011. We performed multilocus sequence typing (MLST) to investigate the genetic relatedness of these C. albicans BSI isolates. A total of 79 episodes of C. albicans BSI in 76 paediatric patients were identified, including 41 (51.9%) from the paediatric intensive care unit, 24 (30.4%) from the neonatal intensive care unit and 14 (17.7%) from general wards. More than half (59.5%) of these patients had underlying chronic co-morbidities, and the majority (94.9%) had a catheter or some other artificial device. All the isolates were susceptible to the antifungal agents tested. Only 32.9% (26/79) received effective antifungal agents within 24 h of onset of candidaemia. Twenty-five (31.6%) patients had persistent candidaemia (>3 days after the start of antifungal treatment) and candidaemia-attributable mortality rate was 22.8% (18/79). The 72 isolates available for MLST yielded 53 unique diploid sequence types (DSTs). Forty-five DSTs were singletons and eight DSTs were shared by 27 (37.5%) isolates. Seventy-one (98.6%) isolates were clustered within previously known clades. Based on the definition of two or more strains with shared DST occurring within a period of 90 days, 10.1% of the infections were categorized as nosocomial clusters, most commonly identified in the intensive care units. Although cluster-associated candidaemia was not associated with a higher mortality rate, none of the clusters were identified by the hospital infection control team.

Predictors of clinical and microbiological treatment failure in neonatal bloodstream infections.

This study aimed to identify independent predictors of clinical and microbiological treatment failure and develop a predictive model for neonates with bloodstream infection (BSI). This study included 1087 episodes of BSIs in 793 neonates in a tertiary-level neonatal intensive care unit of northern Taiwan between 2004 and 2012. Patient demographics, underlying chronic comorbidities, clinical features, antimicrobial treatment and microbiological characteristics were evaluated. The presence of underlying congenital anomalies (odds ratio [OR] 2.12, 95% confidence interval [CI] 1.09 to 4.10) and pulmonary hypertension (OR 3.63, 95% CI 1.70 to 7.74), infections caused by multidrug-resistant gram-negative bacteria (OR 2.89, 95% CI 1.23 to 6.79), group B Streptococcus (OR 3.15, 95% CI 1.33 to 7.46), and fungi (OR 4.13, 95% CI 2.02 to 8.46), a Neonatal Therapeutic Intervention Scoring System score of ≥ 23 (OR 6.96, 95% CI 2.55 to 28.58), inappropriate antibiotics (OR 2.13, 95% CI 1.41 to 3.23), and concomitant meningitis (OR 4.25, 95% CI 2.08 to 8.69) and ventilator-associated pneumonia (OR 2.73, 95% CI 1.22 to 6.13) were identified as independent risk factors for 28-day treatment failure in neonatal BSI. A risk score model was created by adding the points for each independent risk factor, and had a c-statistic of 0.83. Patients with risk scores of 0, 4, 8, 12 and 15 had estimated 28-day treatment failure rates of approximately 3.5%, 17.0%, 53.5%, 86.6% and 95.9%, respectively. This predictive model, calculated after documentation of a BSI, reflects a spectrum of BSI severity and was associated with subsequent treatment failure through illness severity score and case mix variables. This simple score could prove useful in clinical and research settings, and practical in estimating the prognosis.

Hepatitis C transmission from viremic donors in hematopoietic stem cell transplant.

Transmission of hepatitis C virus (HCV) to recipients of hematopoietic stem cell transplant (HSCT) occurs frequently from HCV viremic donors and causes complications. Here, we report the outcomes of 3 cases from our 265 allogeneic HSCTs, whose donors had HCV infections. Successful prevention of HCV transmission was noted in 1 recipient by pretreatment of the donor with peginterferon/ribavirin to undetectable levels of HCV viremia before stem cell harvest. This case stressed the important role of effective antiviral therapy and HCV RNA seronegativity before cell harvest for prevention of HCV transmission in HSCT.

Recurrent late-onset sepsis in the neonatal intensive care unit: incidence, clinical characteristics and risk factors.

We aimed to characterize the incidence, clinical features, risk factors and outcomes of recurrent late-onset sepsis (LOS) in the neonatal intensive care unit (NICU). All neonates with LOS from the NICU of a tertiary-level teaching hospital in northern Taiwan between 2004 and 2011 were enrolled for analyses. A case-control study was performed to determine risk factors for recurrence. Of 713 neonates with LOS, 150 (21.0%) experienced recurrence and 48 (6.7%) had >1 recurrences; c. two-thirds of recurrent LOS occurred in infants with birth weight (BW)≦1500 g or gestational age (GA)≦30 weeks. The recurrent LOS episodes were significantly more severe and had a higher sepsis-attributable mortality rate than the first episodes. The overall in-hospital mortality rate was 30.7% for neonates with recurrent LOS and 7.8% for those with single LOS (odds ratio (OR), 5.22; 95% CI, 3.28-8.30). When both BW and GA were controlled, neonates with recurrent LOS had a significantly prolonged hospitalization compared with the controls (median 109 vs. 84 days, p<0.001). After multivariate logistic regression, longer duration of total parenteral nutrition (TPN; OR, 1.30; 95% CI, 1.10-1.52 for every 10-day increment), presence of congenital anomalies (OR, 2.64; 95% CI, 1.10-6.35) and neurological co-morbidities (OR, 4.14; 95% CI, 1.14-15.10) were identified as the independent risk factors for LOS recurrence. We concluded that c. one-fifth of neonates with LOS had recurrence, which significantly resulted in prolonged hospitalization and increased mortality. Longer TPN administration, presence of congenital anomalies and neurological co-morbidities are independently associated with recurrent LOS.

Prognostic implication of molecular aberrations in cytogenetically normal acute myeloid leukemia patients receiving allogeneic hematopoietic stem cell transplantation.

Different molecular aberrations can be discriminated into certain prognostic subgroups in cytogenetically normal acute myeloid leukemia (CN-AML) patients but their impact on allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains controversial and studies from Asian populations are lacking. Forty-two adult non-M3 AML patients receiving allo-HSCT from 2002 to 2009 in southern Taiwan were retrospectively reviewed for survey, 23 (54.7%) of whom were CN-AML. NPM1, FLT3-ITD, and CEBPA were analyzed. After a median follow-up of 104 weeks (range, 8 to 384), patients in the good risk group (harboring either NPM1 or CEBPA mutation without concurrent FLT3-ITD) showed a borderline worse overall survival (OS) compared with the intermediate/poor risk group (P = 0.08). Interestingly, a poorer OS was found in patients with the CEBPA mutation (P = 0.003) but not the NPM1 mutation (P = 0.96). No OS difference was found between patients with or without FLT3-ITD (P = 0.15). In patients receiving allo-HSCT at first remission, there was no significant OS benefit in the good risk group (P = 0.33). In patients receiving allo-HSCT beyond first remission, disease status played a major role (P = 0.006), irrespective of molecular aberrations. Allo-HSCT in good risk patients should be carefully evaluated in Taiwanese, especially in patients with the CEBPA mutation. Conversely, allo-HSCT should be considered in first remission in patients with an intermediate/poor risk, where it may overcome the adverse impact of FLT3-ITD. Disease status remained a main issue in patients receiving allo-HSCT beyond first remission.

Neonatal lupus complicated by hemorrhagic stroke.

Neonatal lupus is a passively acquired autoimmune syndrome resulting from the transplacental passage of maternal anti-Ro/SSA and/or anti-La/SSB antibodies to the fetus. Few past studies have reported central nervous system involvement in neonatal lupus, and most cases had a good neurological outcome. We report here a preterm case of neonatal lupus with thrombocytopenia and comorbid hemorrhagic stroke. In the follow-up, the infant developed spastic quadriplegia and showed delayed milestones. We believe that this is the first reported case of neonatal lupus accompanied by perinatal hemorrhagic stroke. We present this case to remind clinicians to conduct regular central nervous system surveys in cases of neonatal lupus.

Hypernatremia and grade III/IV intraventricular hemorrhage among extremely low birth weight infants.

OBJECTIVE: To identify the risk factors contributing to intraventricular hemorrhage (IVH) in extremely low birth weight infants during early postnatal life, after appropriate matching for gestational age (GA) and birth body weight (BBW). STUDY DESIGN: A case-control retrospective study was designed to evaluate preterm infants with a GA ≤ 26 weeks and a BBW ≤ 1000 g admitted to our hospital during a 7.5-year period. From a cohort of 347 preterm infants, 36 infants (10.7%) had severe IVH (grades III and/or IV). We selected a control group of 36 preterm infants without IVH who were closely matched for GA (± 1 week) and body weight (± 100 g). Univariate and multivariate logistic regression analyses were performed to identify risk factors for severe IVH. RESULT: The GA and BBW of the IVH and control groups were 24.6 ± 1 weeks and 764.4 ± 118.5 g, and 24.8 ± 0.9 weeks and 771.5 ± 125.9 g, respectively. Vaginal delivery, male sex, resuscitation in the delivery room, high sodium serum levels (meq l(-1)) (162.6 vs 148.8), fluctuation of serum sodium (meq l(-1)) (17.3 vs 6.2), pH, PaCO(2), hemoglobin and platelet counts were associated with an increased risk of severe IVH. Multivariate logistic regression indicated that sodium fluctuations >13 meq l(-1), vaginal delivery, male sex and hemoglobin fluctuations are strongly associated with the development of severe IVH. CONCLUSION: Hypernatremia and fluctuations of sodium seem to be related to early severe IVH among preterm infants; however, further studies are required to clarify the causal relationship.

High variation of PCDDs, PCDFs, and dioxin-like PCBs ratio in cooked food from the first total diet survey in Taiwan.

This study determined the levels of polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/Fs), and dioxin-like polychlorinated biphenyls (dl-PCBs) in 240 individual food samples, belonging to 37 different foodstuffs in first total diet study (TDS) in Taiwan. The foods were collected from markets located in eight cities or counties around Taiwan. The food was cooked in a laboratory according to recipes typically used in Taiwan. In this study, PCDD/Fs were lower than the limits proposed by the European Union (EU) regulation for commercialized food, except for a notable PCDD/Fs level in ducks (3.660 pg WHO-TEQ/g, fat) obtained from central Taiwan. We hypothesize the duck meat might be probably polluted via emission of a fly ash recycling plant located near the duck farms. In addition to fish, most foods had high PCDD/Fs to dl-PCBs ratio. Needle fish and sea perch had relatively lower PCDD/Fs and dl-PCBs levels compared with those in other fish. Data from this study can be utilized for further consideration about dietary intake.

Formaldehyde-treated, heat-inactivated virions with increased human immunodeficiency virus type 1 env can be used to induce high-titer neutralizing antibody responses.

The lack of success of subunit human immunodeficiency virus (HIV) type 1 vaccines to date suggests that multiple components or a complex virion structure may be required. We hypothesized that the failure of current vaccine strategies to induce protective antibodies is linked to the inability of native envelope structures to readily elicit these types of antibodies. We have previously reported on the ability of a formaldehyde-treated, heat-inactivated vaccine to induce modest antibody responses in animal vaccine models. We investigated here whether immunization for HIV with an envelope-modified, formaldehyde-stabilized, heat-inactivated virion vaccine could produce higher-titer and/or broader neutralizing antibody responses. Thus, a clade B vaccine which contains a single point mutation in gp41 (Y706C) that results in increased incorporation of oligomeric Env into virions was constructed. This vaccine was capable of inducing high-titer antibodies that could neutralize heterologous viruses, including those of clades A and C. These results further support the development of HIV vaccines with modifications in native Env structures for the induction of neutralizing antibody responses.

Induction of humoral immune responses following vaccination with envelope-containing, formaldehyde-treated, thermally inactivated human immunodeficiency virus type 1.

The lack of success of subunit human immunodeficiency virus type 1 (HIV-1) vaccines to date suggests that multiple components or a complex virion structure may be required. We previously demonstrated retention of the major conformational epitopes of HIV-1 envelope following thermal treatment of virions. Moreover, antibody binding to some of these epitopes was significantly enhanced following thermal treatment. These included the neutralizing epitopes identified by monoclonal antibodies 1b12, 2G12, and 17b, some of which have been postulated to be partially occluded or cryptic in native virions. Based upon this finding, we hypothesized that a killed HIV vaccine could be derived to elicit protective humoral immune responses. Shedding of HIV-1 envelope has been described for some strains of HIV-1 and has been cited as one of the major impediments to developing an inactivated HIV-1 vaccine. In the present study, we demonstrate that treatment of virions with low-dose formaldehyde prior to thermal inactivation retains the association of viral envelope with virions. Moreover, mice and nonhuman primates vaccinated with formaldehyde-treated, thermally inactivated virions produce antibodies capable of neutralizing heterologous strains of HIV in peripheral blood mononuclear cell-, MAGI cell-, and U87-based infectivity assays. These data indicate that it is possible to create an immunogen by using formaldehyde-treated, thermally inactivated HIV-1 virions to induce neutralizing antibodies. These findings have broad implications for vaccine development.

Enhanced binding of antibodies to neutralization epitopes following thermal and chemical inactivation of human immunodeficiency virus type 1.

Inactivation of viral particles is the basis for several vaccines currently in use. Initial attempts to use simian immunodeficiency virus to model a killed human immunodeficiency virus type 1 (HIV-1) vaccine were unsuccessful, and limited subsequent effort has been directed toward a systematic study of the requirements for a protective killed HIV-1 vaccine. Recent insights into HIV-1 virion and glycoprotein structure and neutralization epitopes led us to revisit whether inactivated HIV-1 particles could serve as the basis for an HIV-1 vaccine. Our results indicate that relatively simple processes involving thermal and chemical inactivation can inactivate HIV-1 by at least 7 logs. For some HIV-1 strains, significant amounts of envelope glycoproteins are retained in high-molecular-weight fractions. Importantly, we demonstrate retention of each of three conformation-dependent neutralization epitopes. Moreover, reactivity of monoclonal antibodies directed toward these epitopes is increased following treatment, suggesting greater exposure of the epitopes. In contrast, treatment of free envelope under the same conditions leads only to decreased antibody recognition. These inactivated virions can also be presented by human dendritic cells to direct a cell-mediated immune response in vitro. These data indicate that a systematic study of HIV-1 inactivation, gp120 retention, and epitope reactivity with conformation-specific neutralizing antibodies can provide important insights for the development of an effective killed HIV-1 vaccine.

Poststreptococcal reactive arthritis: report of one case.

Poststreptococcal reactive arthritis (PSRA) is a clinical syndrome of reactive arthritis. It is associated with recent streptococcal infections, but could not fulfill the revised Jones criteria for acute rheumatic fever (ARF). The incidence of PSRA cardiac complications to develop was as high as the ARF's developing into rheumatic heart disease. A 9-year-old boy presented with limping gait. He had pain in his left knee for 4 days but no fever. His right knee was swelling with a limitation of movement. A throat culture showed positive growth for group A streptococcus, and consequently antistreptolysin-O serum titer and C-reactive protein were elevated. A synovial fluid examination was turbid but sterile. After 3 days the arthralgia subsided rapidly. A cardiac color Doppler and electrocardiogram showed no evidence of valvular disease. Under the threat of high incidence of rheumatic heart disease in PSRA, we treated this patient with prophylactic antibiotics as acute rheumatic fever. A clinic follow up one year later showed neither sequels nor heart murmur on physical examination.

Evidence for reduced cancellous bone mass in the spontaneously hypertensive rat.

The histomorphometric changes in the proximal tibial metaphysis and epiphyseal growth plate and midtibial shaft of 26-week-old spontaneously hypertensive rats (SHR) compared with those of the corresponding normotensive Wistar-Kyoto (WKY) rats were studied. A decrease in body weight, growth plate thickness, and longitudinal growth rate of the proximal tibial epiphysis, trabecular bone volume, trabecular thickness and number, the number of osteoblasts and osteoprogenitor cells per millimeter square surface of the proximal tibial metaphysis, periosteal and endocortical apposition rate and bone formation rate of the tibial diaphysis were observed in the SHR. Additionally, systolic blood pressure, the number of osteoclasts per millimeter square surface and average number of nuclei per osteoclast of the proximal tibial metaphysis were significantly increased. Thus, osteoclastic activity is dominant over osteoblastic and chondroblastic activity in the SHR that results in a cancellous bone deficit in the skeleton. It will require additional work to ascertain the underlying cause for this condition as several factors in the SHR with a potential for causing this change are present, including elevated parathyroid hormone (PTH), depressed 1,25-(OH)2D3, low calcium absorption, reduced body weight (reduced loading) elevated blood pressure and possibly other direct cell differences in the mutant strain. At present elevated PTH and adaptation to underloading from reduced weight are postulated to be a likely cause, but additional studies are required to test this interpretation.

An enzyme-linked immunosorbent assay (ELISA) for measurement of heterophile antibody.

An enzyme-linked immunosorbent assay (ELISA) test has been developed for measurement of heterophile antibody. The microtiter test utilizes a bovine erythrocyte monolayer as antigen and anti-human IgM antiserum conjugated with horseradish peroxidase to measure the degree of binding of the heterophile antibody in the test serum with the erythrocytes. A single serum dilution yields quantitative results when read in a spectrophotometer. The ELISA test showed a sensitivity comparable with the immune adherence hemagglutination assay (IAHA) and other heterophile tests, good reproducibility, and high specificity.