Microwave Susceptibility Observation of Interacting Many-Body Andreev States.

Electrostatic charging affects the many-body spectrum of Andreev states, yet its influence on their microwave properties has not been elucidated. We developed a circuit quantum electrodynamics probe that, in addition to transition spectroscopy, measures the microwave susceptibility of different states of a semiconductor nanowire weak link with a single dominant (spin-degenerate) Andreev level. We found that the microwave susceptibility does not exhibit a particle-hole symmetry, which we qualitatively explain as an influence of Coulomb interaction. Moreover, our state-selective measurement reveals a large, π-phase shifted contribution to the response common to all many-body states which can be interpreted as arising from a phase-dependent continuum in the superconducting density of states.

Coherent manipulation of an Andreev spin qubit.

Two promising architectures for solid-state quantum information processing are based on electron spins electrostatically confined in semiconductor quantum dots and the collective electrodynamic modes of superconducting circuits. Superconducting electrodynamic qubits involve macroscopic numbers of electrons and offer the advantage of larger coupling, whereas semiconductor spin qubits involve individual electrons trapped in microscopic volumes but are more difficult to link. We combined beneficial aspects of both platforms in the Andreev spin qubit: the spin degree of freedom of an electronic quasiparticle trapped in the supercurrent-carrying Andreev levels of a Josephson semiconductor nanowire. We performed coherent spin manipulation by combining single-shot circuit-quantum-electrodynamics readout and spin-flipping Raman transitions and found a spin-flip time T S = 17 microseconds and a spin coherence time T 2E = 52 nanoseconds. These results herald a regime of supercurrent-mediated coherent spin-photon coupling at the single-quantum level.

Are computed tomography-based measures of specific abdominal muscle groups predictive of adverse outcomes in older cancer patients?

PURPOSE: It is unknown whether computed tomography (CT)-based total abdominal muscle measures are representative of specific abdominal muscle groups and whether analysis of specific abdominal muscle groups are predictive of the risk of adverse outcomes in older cancer patients. METHODS: Retrospective single-center cohort study in elective colon cancer patients aged ≥65 years. CT-based skeletal muscle (SM) surface area, muscle density and intermuscular adipose tissue (IMAT) surface area were determined for rectus abdominis; external- and internal oblique and transversus abdominis (lateral muscles); psoas; and erector spinae and quadratus lumborum (back muscles). Outcomes were defined as severe postoperative complications (Clavien-Dindo score >2) and long-term survival (median follow-up 5.2 years). RESULTS: 254 older colon cancer patients were included (median 73.6 years, 62.2% males). Rectus abdominis showed the lowest SM surface area and muscle density and the back muscles showed the highest IMAT surface area. Psoas muscle density, and lateral muscle density and percentage IMAT were associated with severe postoperative complications independent of gender, age and cancer stage. CONCLUSIONS: CT-based total abdominal muscle quantity and quality do not represent the heterogeneity that exists between specific muscle groups. The potential added value of analysis of specific muscle groups in predicting adverse outcomes in older (colon) cancer patients should be further addressed in prospective studies.

High incidence of (ultra)low oesophageal temperatures during cryoballoon pulmonary vein isolation for atrial fibrillation.

BACKGROUND: Low oesophageal temperatures (OTs) during cryoballoon pulmonary vein isolation (PVI) have been associated with complications. This study assessed the incidence of low OT in clinical practice during cryoballoon PVI and verified possible predictive values for low OT. METHODS: Consecutive patients who underwent PVI using the second-generation cryoballoon were retrospectively included. The distance from the oesophagus to the different pulmonary veins (PVs) (OP distance), body mass index (BMI), sex, age, balloon temperature and application time were studied as potential predictors of low OTs. Computed tomography was performed before the procedure to determine the OP distance. OT was measured using an oesophageal temperature probe. Applications were ended prematurely if the OT reached <16 °C. Low and ultralow OT were defined as OT <20 and <16 °C respectively. RESULTS: Two hundred and four patients were included. Low OT was observed in 54 patients (26%) and 27 patients (13%) reached ultralow OTs. OP distance was the only predictor of low OTs after multivariate analysis. A cut-off value of 19 mm showed 96.2% sensitivity and 37.8% specificity in predicting low OTs. No clinically relevant relation was found between low OTs and BMI, age, sex, balloon temperature or application duration. CONCLUSIONS: The incidence of low OT was 26% for cryoballoon PVI. OP distance was the only predictor of low OTs. Since an OP distance <19 mm was present in all patients in at least one PV, we recommend routine OT measurement during PVI cryoballoon therapy to prevent oesophagus-related complications.

Occupational exposure of pharmacy technicians and cleaning staff to cytotoxic drugs in Dutch hospitals.

Many studies into surface contamination of hospital environments have demonstrated that occupational exposure to cytotoxics through the dermal route remains a possible risk. In this study, we assess the actual dermal exposure of the hands of pharmacy technicians and cleaning personnel in a panel of hospitals performing tasks that pose a risk of exposure. We compare the dermal exposure to a tentative limit value for cyclophosphamide. Pharmacy technicians and cleaning personnel were asked for hand rinsing after performance of nine tasks previously identified as posing a risk of occupational exposure. All samples were analyzed for the presence and quantity of eight antineoplastic drugs. By using data on both the frequency of the performance of the tasks and the measured dermal contamination during these tasks, weekly exposure to the marker drug (cyclophosphamide) was calculated. In five Dutch hospitals, 70 hand rinse samples and 8 blanks were collected. These were analyzed and results were used to calculate weekly exposure. The tentative limit value used was 0.74 µg of cyclophosphamide. For cleaning personnel, all results remained below this threshold value. For pharmacy technicians, the compounding itself also remained well below the limit; however, the task involving preparatory work, as well as the checking of compounded drugs, had a 13% chance of exceeding the limit. All of the highest values were found when employees were not wearing gloves on these tasks. Cleaning personnel and pharmacy technicians compounding cytotoxic drugs in our study were sufficiently protected from occupational exposure. In contrast, pharmacy technicians who perform preparatory and finishing tasks (before and after the actual compounding) are not protected enough when they do not wear gloves.

Direct Microwave Measurement of Andreev-Bound-State Dynamics in a Semiconductor-Nanowire Josephson Junction.

The modern understanding of the Josephson effect in mesosopic devices derives from the physics of Andreev bound states, fermionic modes that are localized in a superconducting weak link. Recently, Josephson junctions constructed using semiconducting nanowires have led to the realization of superconducting qubits with gate-tunable Josephson energies. We have used a microwave circuit QED architecture to detect Andreev bound states in such a gate-tunable junction based on an aluminum-proximitized indium arsenide nanowire. We demonstrate coherent manipulation of these bound states, and track the bound-state fermion parity in real time. Individual parity-switching events due to nonequilibrium quasiparticles are observed with a characteristic timescale T_{parity}=160±10 µs. The T_{parity} of a topological nanowire junction sets a lower bound on the bandwidth required for control of Majorana bound states.

Skeletal muscle mass and quality as risk factors for postoperative outcome after open colon resection for cancer.

BACKGROUND: The prevalence of colorectal cancer in the elderly is increasing and, therefore, surgical interventions with a risk of potential complications are more frequently performed. This study investigated the role of low skeletal muscle mass (sarcopenia), muscle quality, and the sarcopenic obesity as prognostic factors for postoperative complications and survival in patients with resectable colon cancer. METHODS: We conducted a retrospective chart review of 91 consecutive patients who underwent an elective open colon resection for cancer with primary anastomosis between 2011 and 2013. Skeletal muscle mass was measured as total psoas area (TPA) and total abdominal muscle area (TAMA) at three anatomical levels on the preoperative CT scan. Skeletal muscle quality was measured using corresponding mean Hounsfield units (HU) for TAMA. Their relation with complications (none vs one or more), severe complications, and survival was analyzed. RESULTS: The study included 91 patients with a mean age of 71.2 ± 9.7 years. Complications were noted in 55 patients (60 %), of which 15 (16.4 %) were severe. Lower HU for TAMA, as an indicator for impaired skeletal muscle quality, was an independent risk factor for one or more complications (all P ≤ 0.002), while sarcopenic obesity (TPA) was an independent risk factor for severe complications (all P ≤ 0.008). Sarcopenia was an independent predictor of worse overall survival (HR 8.54; 95 % confidence interval (CI) 1.07-68.32). CONCLUSION: Skeletal muscle quality is a predictor for overall complications, whereas sarcopenic obesity is a predictor for severe postoperative complications after open colon resection for cancer. Sarcopenia on itself is a predictor for worse overall survival.

Hepatocellular carcinoma after danazol treatment for hereditary angio-oedema.

Hereditary angio-oedema is characterised by recurrent episodes of laryngeal, intra-abdominal, facial or peripheral oedema. Danazol can be used as prophylaxis for recurrent attacks. Hepatotoxicity is a recognised adverse effect of danazol. We report an exceptional case of a danazol-induced hepatocellular carcinoma in a 75-year-old patient with hereditary angio-oedema.

Cauda equina syndrome secondary to complicated diverticulitis.

A 58-year-old woman presented to the emergency department with cauda equina syndrome and sepsis. The symptoms were attributed to a complicated episode of sigmoid diverticulitis. MRI showed that the diverticulitis had caused an intra-abdominal fistula to a presacrally localized abscess expanding into the spinal canal, compressing the cauda equina nerves. Although Hartmann's procedure was performed, the neurological symptoms persisted, causing the patient to remain partially paraplegic. This case report illustrates that cauda equina syndrome is a condition that can also be caused by intra-abdominal pathology such as diverticulitis.

Fusion of two novel genes, RBM15 and MKL1, in the t(1;22)(p13;q13) of acute megakaryoblastic leukemia.

t(1;22) is the principal translocation of acute megakaryoblastic leukemias. Here we show this chromosomal rearrangement to result in the fusion of two novel genes, RNA-binding motif protein-15 (RBM15), an RNA recognition motif-encoding gene with homology to Drosophila spen, and Megakaryoblastic Leukemia-1 (MKL1), a gene encoding an SAP (SAF-A/B, Acinus and PIAS) DNA-binding domain.

Spontaneous blastomere fusion after freezing and thawing of early human embryos leads to polyploidy and chromosomal mosaicism.

The incidence of blastomere fusion after cryopreservation of early human embryos (day 2 and day 3) was investigated using the standard propanediol technique. The process of fusion was observed in all developmental stages (from 2 to 10 cells) and the frequency of this event was 4.6% in day 2 (41/889) and 1.5% in day 3 (10/646) embryos that survived the thawing (embryos with 50-100% intact cells). Fusion of two, and occasionally of several, blastomeres resulted in the formation of multinucleated hybrid cells, which clearly indicated that the ploidy of these newly created cells had been altered. This event, depending on the number of fused cells per embryo, transformed the embryos into either entirely polyploid embryos (complete fusion at 2- or 3-cell stage) or into mosaics being a mixture of polyploid and normal cells. Chromosomal preparations of embryos affected by blastomere fusion indicated the presence of tetraploid mitotic plates. Also, fluorescence in-situ hybridization (FISH) analysis using DNA probes targeting unique sequences on chromosomes 9, 15, 17 and 22 indicated the existence of tetraploid and diploid fluorescence signals in the interphase nuclei within mosaics. Therefore, observations on live and fixed embryos suggested that tetraploid (4n) or hexaploid (6n) and tetraploid-diploid or more complex aberrations of ploidy might be formed as a consequence of blastomere fusion. Furthermore, this demonstrates that freezing and thawing may induce numerical chromosomal changes in human embryos.

[Growth retardation as a result of a presumption of multiple food hypersensitivity]. / Groeiachterstand als gevolg van vermeende voedselovergevoeligheid.

Two sisters, aged 5 and 6 years, were admitted to the hospital because of growth retardation accompanying supposed multiple food hypersensitivity. The older girl had asthma. Her symptoms had given cause for several non-regular practitioners to diagnose her and subsequently her sister as having 'food hypersensitivity'. The diet they were put on was further restricted by their parents when the symptoms did not subside. The diet was shown to be very monotonous and the energy supply was only half of the recommended daily allowances. Stepwise normalization of the diet was achieved and both girls showed catch-up growth in the following years. Food hypersensitivity has a considerably higher incidence when self reported than when diagnosed according to established criteria (elimination, provocation, re-elimination). Dietary changes in children should always take place under the supervision of a dietician, who can ensure that the diet is nutritionally adequate.

Clonal heterogeneity of dendritic cells derived from patients with chronic myeloid leukemia and enhancement of their T-cells stimulatory activity by IFN-alpha.

Adoptive immunotherapy in form of donor leukocyte infusions is effective in a significant number of patients with chronic myeloid leukemia (CML) that have relapsed after allogeneic bone marrow transplantation (BMT). However, the therapy is associated with clinically significant side effects such as graft-versus-host disease (GVHD) and bone marrow (BM) hypoplasia that may be avoided through the administration of T cells with specific antileukemic activity. Dendritic cells (DC) functioning as potent antigen presenting cells (APC) may play an important role in the generation of T cells with specificity against CML. We examined a subpopulation of CD1a+/CD14- DC generated in vitro from BM of normal subjects and patients with CML using granulocyte-macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor-alpha (TNF-alpha) and interleukin-4 (IL-4). These DC derived from both the BM of normal subjects and of patients with CML, differentiated and matured in culture in a similar way. However, DC derived from patients with CML, displayed decreased activity when tested with allogeneic T cells in a mixed lymphocyte reaction (MLR). Addition of interferon-alpha (IFN-alpha) to DC cultures significantly upregulated the expression of major histocompatibility complex (MHC) molecules (class I and class II) and costimulatory molecules (B7.1 and B7.2) on DC from normal donors and CML patients. However, DC grown from CML patients required a higher concentration of IFN-alpha. IFN-alpha also significantly improved the capacity of CML DC to stimulate T-lymphocyte responses. Fluorescence in situ hybridization (FISH) showed that only some CD1a+/CD14- DC derived from BM of patients with CML expressed the bcr/abl fusion gene. Incubation with INF-alpha decreased the proportion of bcr/abl positive DC.

Frequent monoallelic loss of D13S319 in multiple myeloma patients shown by interphase fluorescence in situ hybridization.

Deletions or monosomy of chromosome 13 are frequent in multiple myeloma (MM). A candidate tumor suppressor gene might reside telomeric of the retinoblastoma gene (RBl) at band 13q14 and to play a role in B cell neoplasm. The D13S319 locus, between RB1 and D13S25 loci at 13q14 is the most commonly deleted marker in chronic lymphocytic leukemia (CLL) and non-Hodgkin's lymphoma (NHL). We evaluated the D13S319 locus in 24 MM cases by fluorescence in situ hybridization (FISH). We observed monosomy for D13S319 in 6/20 (30%) MM patients with an apparently normal karyotype. As expected, in four karyotypically abnormal MM cases with partial or complete monosomy for chromosome 13, all of them had monoallelic loss of D13S319. Our results indicated that the loss of D13S319 is commonly found in MM, even at diagnosis, and is more frequent than predicted based on conventional cytogenetic analysis of metaphase spreads. This finding implicates a candidate tumor suppressor gene at 13q14 in the pathogenesis of MM.

Pictorial superiority during verbal learning tasks in moderate to severe closed head injury: additional evidence.

Evidence for picture superiority in verbal learning following moderate to severe closed head injury (CHI) was found in a study involving 31 participants with CHI and 31 noninjured participants. A multitrial free-recall paradigm was implemented incorporating three modalities: Auditory, visual, and simultaneous auditory plus visual. Participants with moderate to severe CHI learned fewer words and at a slower rate than the noninjured participants. The visual presentation of objects (with or without the simultaneous auditory presentation of names) resulted in better learning than the auditory presentation alone.

The comparability of the WRAT-R reading test and NAART as estimates of premorbid intelligence in neurologically impaired patients.

A study by Wiens, Bryan, and Crossen (1993) suggests the Wide Range Achievement Test-Revised (WRAT-R) Reading subtest and North American Adult Reading Test (NAART) are adequate predictors of Wechsler Adult Intelligence Scale-Revised (WAIS-R) IQ scores for a normal population. Although it is common practice to use reading scores to estimate premorbid IQ in clinical populations, the WRAT-R and NAART have not been compared using individuals with brain dysfunction. The current study cross-validated the Wiens et al. (1993) study using neurologically impaired populations: traumatic brain injury (n = 118), dementia (n = 37), and other neurologic impairments (n = 77). The results were generally consistent across all three groups: (a) the WRAT-R and NAART were equivalent and accurate estimates of average VIQ levels; (b) the WRAT-R and NAART were equivalent but underestimates of higher intelligence ranges; and (c) the WRAT-R is a more accurate estimate for lower VIQ ranges, although both are overestimates. This third finding is in contrast to Wiens et al.'s (1993) results that suggest the WRAT-R is an accurate estimate of lower IQ ranges for normals. It is concluded that the WRAT-R is the preferred measure of premorbid verbal intelligence for psychometric and clinical reasons.

Organization of the Saccharomyces cerevisiae actin gene UAS: functional significance of reiterated REB1 binding sites and AT-rich elements.

The upstream activation sequence (UAS) in the Saccharomyces cerevisiae actin gene promoter contains three different motifs, specifically two AT-rich tracts, two binding sites for the yeast protein REB1, and an Mlul site. Synthetic UAS elements containing individual motifs, or combinations of them, were inserted in place of the natural UAS, and assayed using a lacZ reporter gene. The REB1 binding sites were found to be essential for, and sufficient to restore partial, UAS activity. AT-rich tracts alone were inactive. Multimerization of a REB1 binding site created a UAS that in galactose is more active, but in glucose less active, than a UAS having a single REB1 site with one AT-rich tract. In general, transcription during growth in galactose or glycerol/lactate responds more to multimerization of motifs. The results suggest that the natural actin promoter UAS retains activity on these alternative carbon sources because of reiteration of sequence elements within it; the additional elements appear to be redundant when cells are grown on glucose. The Mlul site, which is present upstream of a number of yeast genes involved in DNA synthesis and confers cell cycle periodicity to those genes, contributes to the activity of the synthetic UAS elements, but not in a cell-cycle-dependent manner.