Nuclear quantum effect with pure anharmonicity and the anomalous thermal expansion of silicon.

Despite the widespread use of silicon in modern technology, its peculiar thermal expansion is not well understood. Adapting harmonic phonons to the specific volume at temperature, the quasiharmonic approximation, has become accepted for simulating the thermal expansion, but has given ambiguous interpretations for microscopic mechanisms. To test atomistic mechanisms, we performed inelastic neutron scattering experiments from 100 K to 1,500 K on a single crystal of silicon to measure the changes in phonon frequencies. Our state-of-the-art ab initio calculations, which fully account for phonon anharmonicity and nuclear quantum effects, reproduced the measured shifts of individual phonons with temperature, whereas quasiharmonic shifts were mostly of the wrong sign. Surprisingly, the accepted quasiharmonic model was found to predict the thermal expansion owing to a large cancellation of contributions from individual phonons.

On real-valued SDE and nonnegative-valued SDE population models with demographic variability.

Population dynamics with demographic variability is frequently studied using discrete random variables with continuous-time Markov chain (CTMC) models. An approximation of a CTMC model using continuous random variables can be derived in a straightforward manner by applying standard methods based on the reaction rates in the CTMC model. This leads to a system of Itô stochastic differential equations (SDEs) which generally have the form [Formula: see text] where [Formula: see text] is the population vector of random variables, [Formula: see text] is the drift vector, and G is the diffusion matrix. In some problems, the derived SDE model may not have real-valued or nonnegative solutions for all time. For such problems, the SDE model may be declared infeasible. In this investigation, new systems of SDEs are derived with real-valued solutions and with nonnegative solutions. To derive real-valued SDE models, reaction rates are assumed to be nonnegative for all time with negative reaction rates assigned probability zero. This biologically realistic assumption leads to the derivation of real-valued SDE population models. However, small but negative values may still arise for a real-valued SDE model. This is due to the magnitudes of certain problem-dependent diffusion coefficients when population sizes are near zero. A slight modification of the diffusion coefficients when population sizes are near zero ensures that a real-valued SDE model has a nonnegative solution, yet maintains the integrity of the SDE model when sizes are not near zero. Several population dynamic problems are examined to illustrate the methodology.

Systems based analysis of human embryos and gene networks involved in cell lineage allocation.

BACKGROUND: Little is understood of the molecular mechanisms involved in the earliest cell fate decision in human development, leading to the establishment of the trophectoderm (TE) and inner cell mass (ICM) stem cell population. Notably, there is a lack of understanding of how transcriptional networks arise during reorganisation of the embryonic genome post-fertilisation. RESULTS: We identified a hierarchical structure of preimplantation gene network modules around the time of embryonic genome activation (EGA). Using network models along with eukaryotic initiation factor (EIF) and epigenetic-associated gene expression we defined two sets of blastomeres that exhibited diverging tendencies towards ICM or TE. Analysis of the developmental networks demonstrated stage specific EIF expression and revealed that histone modifications may be an important epigenetic regulatory mechanism in preimplantation human embryos. Comparison to published RNAseq data confirmed that during EGA the individual 8-cell blastomeres are transcriptionally primed for the first lineage decision in development towards ICM or TE. CONCLUSIONS: Using multiple systems biology approaches to compare developmental stages in the early human embryo with single cell transcript data from blastomeres, we have shown that blastomeres considered to be totipotent are not transcriptionally equivalent. Furthermore we have linked the developmental interactome to individual blastomeres and to later cell lineage. This has clinical implications for understanding the impact of fertility treatments and developmental programming of long term health.

Long term use of hydraulic artificial urethral sphincters in nine dogs from New Zealand with urethral sphincter mechanism incompetence.

AIMS: To report on the long-term outcomes of hydraulic artificial urethral sphincter (HAUS) placement for the correction of urethral sphincter mechanism incompetence (USMI) in New Zealand dogs. METHODS: Retrospective data were obtained from cases of dogs which had a HAUS placed after failed medical and/or surgical management of USMI between August 2012 and November 2016. Owner assessment of urinary incontinence was evaluated by an online survey in May 2017 using a visual analogue scale (0 being normal, 100 being severely affected) for the frequency, volume and severity of any straining to urinate, immediately prior to the placement of the HAUS and at the time of the survey. The number of days between surgery and the completion of survey were recorded. RESULTS: Seven females and two male dogs, which were all desexed except for one female, were eligible for inclusion in the study. The period of follow-up following HAUS placement ranged from 206-1,685 days. Following HAUS placement, frequency and volume of urinary incontinence decreased for six dogs and were practically unchanged for three dogs. The median frequency score decreased from 70 to 13 and the volume score decreased from 73 to 12. There was no consistent change in the perceived degree of straining to urinate. Complications occurred in three dogs; one required repositioning of a dislodged injection port, one required management for haematuria and a hypoplastic bladder, and one required surgical removal of fibrous tissue around the HAUS cuff. CONCLUSIONS AND CLINICAL RELEVENCE: HAUS placement was an effective method for the treatment of persistent USMI in most dogs and provided good clinical results based on owner assessment. The technique was associated with few complications and allowed successful long-term control of urinary incontinence without the need for medical management.

Prevention of allograft HCV recurrence with peri-transplant human monoclonal antibody MBL-HCV1 combined with a single oral direct-acting antiviral: A proof-of-concept study.

Patients with active hepatitis C virus (HCV) infection at transplantation experience rapid allograft infection, increased risk of graft failure and accelerated fibrosis. MBL-HCV1, a neutralizing human monoclonal antibody (mAb) targeting the HCV envelope, was combined with a licensed oral direct-acting antiviral (DAA) to prevent HCV recurrence post-transplant in an open-label exploratory efficacy trial. Eight subjects received MBL-HCV1 beginning on the day of transplant with telaprevir initiated between days 3 and 7 post-transplantation. Following FDA approval of sofosbuvir, two subjects received MBL-HCV1 starting on the day of transplant with sofosbuvir initiated on day 3. Combination treatment was administered for 8-12 weeks or until the stopping rule for viral rebound was met. The primary endpoint was undetectable HCV RNA at day 56 with exploratory endpoints of sustained virologic response (SVR) at 12 and 24 weeks post-treatment. Both subjects receiving mAb and sofosbuvir achieved SVR24. Four of eight subjects in the mAb and telaprevir group met the primary endpoint; one subject achieved SVR24 and three subjects relapsed 2-12 weeks post-treatment. The other four subjects experienced viral breakthrough. There were no serious adverse events related to study treatment. This proof-of-concept study demonstrates that peri-transplant immunoprophylaxis combined with a single oral direct-acting antiviral in the immediate post-transplant period can prevent HCV recurrence.

Human monoclonal antibody MBL-HCV1 delays HCV viral rebound following liver transplantation: a randomized controlled study.

Rapid allograft infection complicates liver transplantation (LT) in patients with hepatitis C virus (HCV). Pegylated interferon-α and ribavirin therapy after LT has significant toxicity and limited efficacy. The effect of a human monoclonal antibody targeting the HCV E2 glycoprotein (MBL-HCV1) on viral clearance was examined in a randomized, double-blind, placebo-controlled pilot study in patients infected with HCV genotype 1a undergoing LT. Subjects received 11 infusions of 50 mg/kg MBL-HCV1 (n=6) or placebo (n=5) intravenously with three infusions on day of transplant, a single infusion on days 1 through 7 and one infusion on day 14 after LT. MBL-HCV1 was well-tolerated and reduced viral load for a period ranging from 7 to 28 days. Median change in viral load (log10 IU/mL) from baseline was significantly greater (p=0.02) for the antibody-treated group (range -3.07 to -3.34) compared to placebo group (range -0.331 to -1.01) on days 3 through 6 posttransplant. MBL-HCV1 treatment significantly delayed median time to viral rebound compared to placebo treatment (18.7 days vs. 2.4 days, p<0.001). As with other HCV monotherapies, antibody-treated subjects had resistance-associated variants at the time of viral rebound. A combination study of MBL-HCV1 with a direct-acting antiviral is underway.

Retention of drug administration skills after intensive teaching.

We have identified deficiencies in medical students' drug administration skills, and we attempted to address them with interactive online teaching modules and simulated critical incident scenarios. Short-term improvements have been evident with this intensive effort, but medium-term retention of skills has not been measured. A drug administration lecture, an online module and a simulated emergency scenario were offered to final year clinical students. None of the teaching was compulsory but participation was recorded, along with students' simulator performances and marks in an objective structured practical examination 9 months later. A poor simulator score predicted a poor performance in the later examination. Participation in the simulated scenario only significantly improved examination scores when supplemented by online teaching (p = 0.002). Intensive drug administration teaching using an online module and high fidelity simulation improves drug administration skills in the medium term. Students found simulation much more engaging than online teaching.

Maxillary unicystic ameloblastoma in a 6-week-old filly evaluated with computed tomography.

CASE REPORT: A 6-week-old Thoroughbred filly was presented for evaluation of an expansile mass overlying the right nasal passage and causing respiratory stertor. On skull radiographs, there was a loculated, soft tissue-opaque mass identified dorsal to the right upper premolars and effacing the right nasal cavity. Computed tomography (CT) revealed a locally extensive mass with relatively benign characteristics located centrally on the tooth root apices of the deciduous second premolar (506). The mass extended axially into the right nasal cavity, occluding the meatuses and causing displacement of the nasal septum to the left. CLINICAL OUTCOME & SIGNIFICANCE: Surgical excision was not deemed feasible with an athletic future in mind and the owners elected to euthanase the filly. Histopathologically, the mass was consistent with unicystic ameloblastoma and was lined intermittently with palisading, columnar basal cells (ameloblast-like cells) overlying a zone containing stellate cells in loose stroma. To the authors' knowledge this is the first report of a CT scan of an equine ameloblastoma. Although histopathology was essential for definitive diagnosis, CT clearly defined the origin of the mass and identified its locally extensive, cystic nature, which enabled informed decisions to be made.

Design and operating characteristic of a vacuum furnace for time-of-flight inelastic neutron scattering measurements.

We present the design and operating characteristics of a vacuum furnace used for inelastic neutron scattering experiments on a time-of-flight chopper spectrometer. The device is an actively water cooled radiant heating furnace capable of performing experiments up to 1873 K. Inelastic neutron scattering studies performed with this furnace include studies of phonon dynamics and metallic liquids. We describe the design, control, characterization, and limitations of the equipment. Further, we provide comparisons of the neutron performance of our device with commercially available options. Finally we consider upgrade paths to improve performance and reliability.

Emergency tracheal catheterization for jet ventilation: a role for the ENT surgeon?

Stridor causing respiratory failure is an ENT and anaesthetic emergency requiring prompt management to secure a clear airway. We describe a case of subacute partial upper airway obstruction due to a large laryngeal carcinoma in an 81-year-old male resulting in respiratory failure. The patient became apnoeic after gaseous induction of general anaesthesia, and after two failed intubation attempts an emergency transtracheal airway catheter was placed by the surgeon under direct vision below the cricothyroid membrane, as this had tumour involvement. The patient was subsequently manually jet-ventilated with ease until a formal tracheostomy was made. Where difficulties with tracheal anatomy are encountered due to the presence of pathology, the insertion of a temporary airway catheter for jet ventilation by the surgeon can buy valuable time and be life-saving.

Investigating development of infective stage larvae of filarial nematodes.

Lymphatic filariasis is a parasitic disease affecting millions of individuals and one of the leading causes of disability in the world. However, considering the magnitude of filariasis as a public health problem, relatively little is known about the basic biology of the disease and its causative agents, filarial nematodes. In this paper, the biology of the infective stage larvae of the nematodes responsible for lymphatic filariasis and the approaches used to study their development are reviewed.

Pharmacology and neurochemistry of nefazodone, a novel antidepressant drug.

Nefazodone is a new antidepressant drug with a pharmacologic profile distinct from that of the tricyclic, monoamine oxidase inhibitor, and serotonin selective reuptake inhibitor antidepressants. Nefazodone was initially discovered for its ability to block 5-HT2A receptors and its reduced potency as an alpha 1-adrenergic blocker. It was later shown to inhibit both serotonin and norepinephrine uptake in vitro, attributes which most likely impart its clinical efficacy and which differentiate nefazodone from its chemical predecessor trazodone. The combination of these two mechanisms may ultimately result in a facilitation of 5-HT1A-mediated neurotransmission, which may be beneficial for treating symptoms of depression as evidenced by recent clinical findings. In addition, the preclinical profile of nefazodone demonstrates that it has decreased anticholinergic and antihistaminic activity relative to traditional agents. Clinical findings to date are consistent with these observations.

The role of functional status in predicting inpatient mortality with AIDS: a comparison with current predictors.

To assess the independent prognostic role of functional status, as reflected by a measure of an inpatient's global requirement for nursing assistance with basic activities of daily living (Global ADL), we compared Global ADL with three validated AIDS mortality predictors: the Clinical AIDS Prognostic Staging (CAPS); the Severity Classification System for AIDS Hospitalization--version 2 (SCAH-2); and CD4 cell count. Our study sample consisted of 1392 patients with AIDS and a hospital stay of 3 or more days at one of 20 hospitals in 11 U.S. cities with high AIDS incidence. Data were collected from September 1990 through December 1991. Two percent of patients refused participation, and 26% were eliminated due to incomplete data collection, leaving an analytic sample of 1003 patients. Only 30% of patients had a CD4 count measured at any time during hospitalization. Cox regression was used to measure the hazard of inpatient mortality adjusted for length of stay. Overall mortality was 12%. Mortality rates for patients in Global ADL stages I-IV were 3%, 8%, 19%, and 51%, respectively (p < 0.0001). Global ADL more effectively discriminated mortality than CAPS (p < 0.001), SCAH-2 (p < 0.001), or CD4 count (p < 0.001). Global ADL also added independent information in analyses adjusted for both CAPS and SCAH-2: a single stage increase of Global ADL demonstrated a 1.9-fold increased hazard of death (CI: 1.6, 2.3). SCAH-2, assigned at discharge, was not strongly correlated with admission predictors (Global ADL: r = 0.17; CI: 0.11, 0.23 or CAPS: r = 0.03, CI: 0.02, 0.17). We conclude that Global ADL, alone or in tandem with other severity systems, provides an excellent severity adjustment for inpatient mortality with AIDS. Finally, CD4 cell counts were not routinely available and were not as predictive as Global ADL in the patients for whom both were available.

Costs and cost containment in nursing homes.

The study examines the impact of structural and process variables on the cost of nursing home care and the utilization of various cost containment methods in 43 california nursing homes. Several predictors were statistically significant in their relation to cost per patient day. A diverse range of cost containment techniques was discovered along with strong predictors of the utilization of these techniques by nursing home administrators. The trade-off between quality of care and cost of care is discussed.

Responses to prospective payment by rural New Mexico hospitals.

A cross-sectional study is used to determine how rural New Mexico hospitals altered service diversification, inpatient service emphasis, and service promotion during Medicare's prospective payment system (PPS) transition and posttransition phases. Results suggest that the hospitals implemented distinct strategies in response to PPS. The posttransition strategies were examined for their association with improved revenue and utilization indicators. Few of the service diversification and promotional strategies were consistent predictors of performance. Emphasis on fine-tuning inpatient services was the most promising predictor of higher utilization and revenue measures. The implications for other rural hospitals are discussed.

Microbial Competition in Reactors with Wall Attachment.

Competition for nutrient and the ability of bacteria to colonize the gut wall are factors believed to play a role in the observed stability of the indigenous microbiota of the mammalian large intestine. These factors were incorporated into the two-strain continuous-stirred tank reactor (CSTR) model formulated and numerically investigated by Freter et al. In their model simulations, the reactor is parameterized using data for the mouse intestine. An invading bacterial strain is introduced into a CSTR that has already been colonized by a resident strain. The two strains compete for a single growth-limiting nutrient and for limited adhesion sites on the wall of the reactor. The mathematical model described in this paper is motivated in part by the CSTR model, but is based on the plug flow reactor (PFR). Parameter values and initial conditions are chosen so that the numerical performance of the PFR can be compared to that of the CSTR. In simulations bearing a remarkable qualitative and quantitative resemblance to those of the CSTR it is found that the invader is virtually eliminated, despite the fact that it has uptake rate and affinity for the wall identical to those of the resident. The PFR model is then parametrized using data for the human large intestine, and the two-strain simulations are repeated. Though obvious quantitative differences are noted, the more important qualitative outcome is preserved. It is also found that when three strains compete for a single nutrient and for adhesion sites there exists a steady-state solution characterized by the segregation of the bacterial strains into separate nonoverlapping segments along the wall of the reactor.

Medical ethics in the primary care setting.

Much popular and professional understanding of 'medical ethics' is nowadays located in quandary ethics, exotic life-and-death decision-making, and tertiary care settings. Medical ethics in the primary care setting is concerned with very different matters. Among these are issues having to do with basic self-understandings of health professionals and patients and their fiduciary relationships; with fundamental social, political and economic notions which will and do shape the allocation and distribution of health care resources; with the goals and purposes appropriate to medical interventions of various sorts; and with the care of the whole person rather than the limited attention to a particular illness or disease syndrome. The commitments of primary care medicine challenge in radical ways some cherished claims of modern liberal societies by questioning the limits of autonomous individualism and by affirming the indispensability of social justice.

Managing medical supply logistics among health workers in Ecuador.

Operations research techniques are being used to solve business and government problems throughout the world. This paper discusses the use of an analytical technique--the location set covering algorithm--to determine placement of medical supply centers in Ecuador. By establishing the optimum location of supply centers it is possible to effectively utilize scarce health care resources in a developing country and to help community level health workers be better prepared to deliver primary health care services.

Non-invasive assessment of shunt and ventilation/perfusion ratio in neonates with pulmonary failure.

AIMS: To make non-invasive measurements of right to left (R-L) shunt and reduced ventilation/perfusion ratio (V(A)/Q) in neonates with pulmonary failure and to examine sequential changes in these variables after treatment. METHODS: Twelve neonates with pulmonary failure were studied. They ranged in gestational age from 24 to 37 (median 27) weeks and were 1-39 (median 4) days old. Shunt and reduced V(A)/Q were derived from their effects on the relation between inspired oxygen pressure (PIO(2)) and arterial oxygen saturation measured with a pulse oximeter (SpO(2)). Pairs of PIO(2) v. SpO(2) data points were obtained by varying PIO(2) in a stepwise fashion. A computer algorithm based on a model of pulmonary gas exchange fitted a curve to these data. With PIO(2) on the abscissa, an increase in shunt produced a downward movement of the curve, whereas reducing V(A)/Q to < 0.8 shifted the curve to the right. The right shift gives a variable that is inversely related to V(A)/Q, the PIO(2) - PO(2) difference, where PO(2) is mixed capillary oxygen pressure. RESULTS: Ten of the 12 infants on the first study day had large shunts (range 5.9-31.0%, median 19.9%, normal < 8%) and large PIO(2) - PO(2) differences (range 9.7-64.4 kPa, median 19.8 kPa, normal < 7 kPa) equivalent to a median V(A)/Q of 0.2 (normal median V(A)/Q = 0.8). Sequential improvement in shunt and V(A)/Q were shown in most infants after treatment. Sudden large changes in these variables were shown in two infants. CONCLUSION: This simple non-invasive method distinguishes between shunt and reduced V(A)/Q in neonates with pulmonary failure.