Optimizing Jastrow factors for the transcorrelated method.

We investigate the optimization of flexible tailored real-space Jastrow factors for use in the transcorrelated (TC) method in combination with highly accurate quantum chemistry methods, such as initiator full configuration interaction quantum Monte Carlo (FCIQMC). Jastrow factors obtained by minimizing the variance of the TC reference energy are found to yield better, more consistent results than those obtained by minimizing the variational energy. We compute all-electron atomization energies for the challenging first-row molecules C2, CN, N2, and O2 and find that the TC method yields chemically accurate results using only the cc-pVTZ basis set, roughly matching the accuracy of non-TC calculations with the much larger cc-pV5Z basis set. We also investigate an approximation in which pure three-body excitations are neglected from the TC-FCIQMC dynamics, saving storage and computational costs, and show that it affects relative energies negligibly. Our results demonstrate that the combination of tailored real-space Jastrow factors with the multi-configurational TC-FCIQMC method provides a route to obtaining chemical accuracy using modest basis sets, obviating the need for basis-set extrapolation and composite techniques.

Differentiating Total- or Partial-Body Irradiation in Baboons Using mRNA Expression Patterns: A Proof of Concept.

To better predict clinical outcome after radiation exposure, it is very important to know the absorbed dose and body areas exposed. Previously we found that 22 miRNAs appeared to predict total- and partial-body irradiation (TBI and PBI, respectively) patterns and were suggestive of the percentage of the body exposed in a baboon model. Motivated by these results, we performed a similar analysis on the transcriptional level (mRNAs) using whole genome microarrays. From 17 irradiated baboons, blood samples were taken before, and at 1, 2, 7, 28 and 75-106 days postirradiation to an equivalent TBI dose of 2.5 or 5 Gy applied either to the total body or to different parts of the body such as the upper body (UBE) or left hemibody (LHB). We compared quantile normalized log2-transformed gene expression values with three exposure pattern comparisons, namely TBI vs. PBI, TBI vs. LHB and UBE vs. LHB using Kruskal-Wallis and logistic regression analysis for receiver-operator characteristic (ROC) calculation. We found several hundred significantly (P < 0.05) and ≥2-fold deregulated mRNAs per exposure pattern comparison with a peak of 163-860 mRNAs at day 28. Lower numbers on day 2 (60 mRNAs) and day 7 (91-162 mRNAs) were observed, with the lowest number of deregulated mRNAs at day 75-106 (22-58 mRNAs). The 14 most promising mRNAs (e.g., LTF, DEFA3, OLFM4) appeared 10.1-46.2-fold upregulated and the exposure groups were completely or almost completely discriminated (ROC between 0.8-1.0). Several of the mRNA gene expression changes were significantly associated with the percentage of the body exposed. The numbers of overlapping genes used for diagnosis on consecutive days postirradiation were mostly 0 or less than 10. Bioinformatic analysis confirmed that at each time point different biological processes predominated. Our results suggest mRNA changes over time may be used to retrospectively determine radiation exposure patterns as partial or total body. mRNA gene expression changes likely could be applied over a longer time frame (2-75 days postirradiation) than miRNA, but due to the transient gene expression changes a different set of candidate mRNAs appears to be required at each day after irradiation.

miRNA Expression Patterns Differ by Total- or Partial-Body Radiation Exposure in Baboons.

In a radiation exposure event, a likely scenario may include either total-body irradiation (TBI) or different partial-body irradiation (PBI) patterns. Knowledge of the exposure pattern is expected to improve prediction of clinical outcome. We examined miRNA species in 17 irradiated baboons receiving an upper-body, left hemibody or total-body irradiation of 2.5 or 5 Gy. Blood samples were taken before irradiation and at 1, 2, 7, 28 and 75-106 days after irradiation. Using a qRT-PCR platform for simultaneous detection of 667 miRNAs, we identified 55 miRNAs over all time points. Candidate miRNAs, such as miR-17, miR-128 or miR-15b, significantly discriminated TBI from different PBI exposure patterns, and 5-to-10-fold changes in gene expression were observed among the groups. A total of 22 miRNAs (including miR-17) revealed significant linear associations of gene expression changes with the percentage of the exposed body area (P < 0.0001). All these changes were primarily observed at day 7 postirradiation and almost no miRNAs were detected either before or after 7 days. A significant association in the reduction of lymphocyte counts in TBI compared to PBI animals corresponded with the number of miRNA candidates. This finding suggests that our target miRNAs predominantly originated from irradiated lymphocytes. In summary, gene expression changes in the peripheral blood provided indications of the exposure pattern and a suggestion of the percentage of the exposed body area.

Microstructured Nickel-Titanium Thin Film Leaflets for Hybrid Tissue Engineered Heart Valves Fabricated by Magnetron Sputter Deposition.

Heart valves are constantly exposed to high dynamic loading and are prone to degeneration. Therefore, it is a challenge to develop a durable heart valve substitute. A promising approach in heart valve engineering is the development of hybrid scaffolds which are composed of a mechanically strong inorganic mesh enclosed by valvular tissue. In order to engineer an efficient, durable and very thin heart valve for transcatheter implantations, we developed a fabrication process for microstructured heart valve leaflets made from a nickel-titanium (NiTi) thin film shape memory alloy. To examine the capability of microstructured NiTi thin film as a matrix scaffold for tissue engineered hybrid heart valves, leaflets were successfully seeded with smooth muscle cells (SMCs). In vitro pulsatile hydrodynamic testing of the NiTi thin film valve leaflets demonstrated that the SMC layer significantly improved the diastolic sufficiency of the microstructured leaflets, without affecting the systolic efficiency. Compared to an established porcine reference valve model, magnetron sputtered NiTi thin film material demonstrated its suitability for hybrid tissue engineered heart valves.

Cell adhesion on NiTi thin film sputter-deposited meshes.

Scaffolds for tissue engineering enable the possibility to fabricate and form biomedical implants in vitro, which fulfill special functionality in vivo. In this study, free-standing Nickel­Titanium(NiTi) thin film mesheswere produced by means of magnetron sputter deposition.Meshes contained precisely defined rhombic holes in the size of 440 to 1309 µm2 and a strut width ranging from 5.3 to 9.2 µm. The effective mechanical properties of the microstructured superelastic NiTi thin film were examined by tensile testing. These results will be adapted for the design of the holes in the film. The influence of hole and strut dimensions on the adhesion of sheep autologous cells (CD133+) was studied after 24 h and after seven days of incubation. Optical analysis using fluorescence microscopy and scanning electron microscopy showed that cell adhesion depends on the structural parameters of the mesh. After 7 days in cell culture a large part of the mesh was covered with aligned fibrous material. Cell adhesion is particularly facilitated on meshes with small rhombic holes of 440 µm2 and a strut width of 5.3 µm. Our results demonstrate that free-standing NiTi thin film meshes have a promising potential for applicationsin cardiovascular tissue engineering, particularly for the fabrication of heart valves.

Evidence-based lifestyle interventions in the workplace--an overview.

BACKGROUND: Lifestyle-related health issues affect the economic position of organizations and contribute to reduced productivity, increased absenteeism and health care costs. AIMS: To summarize the effectiveness of different workplace health interventions for promoting healthy lifestyle, preventing diseases and reducing health care costs. METHODS: We searched MEDLINE via Pubmed, EMBASE, Cochrane Library, NelH, HighWire Press and Google Scholar in March 2012. Systematic reviews and meta-analyses of workplace interventions aimed at promoting physical activity, healthy weight and good nutrition were included. Three authors assessed the quality of the reviews and extracted data on methods, interventions, outcomes, results and effect sizes. RESULTS: We identified 15 publications covering a total of 379 original studies. Three systematic reviews found beneficial effects of workplace nutrition interventions on employees' dietary behaviour. Three reviews found multi-component physical activity interventions to be effective in increasing employees' physical activity and fitness. The other activity promotion interventions were less effective regarding physical activity and weight-related outcomes. In terms of weight management, our findings favour multi-component interventions that focus on both physical activity and nutrition over single dietary programmes. CONCLUSIONS: Workplace health promotion interventions may improve physical activity, dietary behaviour and healthy weight. There is no evidence of increased efficacy associated with specific intervention types. Workplace health promotion should focus on either physical activity or weight or nutrition behaviour to maximize effectiveness. Best evidence is available for multi-component interventions.

Surgical treatment of colic in the miniature horse: a retrospective study of 57 cases (1993-2006).

REASONS FOR PERFORMING STUDY: It has been suggested that the rate of post operative abdominal adhesions in miniature horses is higher than that for other breeds. However, few reports exist in the veterinary literature describing complications and long-term survival following surgical treatment of colic in these horses. OBJECTIVES: To determine the prevalence of surgical lesions in miniature horses with acute abdominal disease in terms of clinical signs, surgical management, post operative treatment and complications, as well as short- and long-term survival. METHODS: Medical records of 57 American Miniature Horses undergoing surgical treatment for acute abdominal pain at the Michigan State University Large Animal Veterinary Teaching Hospital 1993-2006 were evaluated for clinical information. Owners and trainers were contacted to gain information regarding long-term survival. RESULTS: The most common surgical lesion was a faecalith (38/57 cases) located primarily within the descending colon and most frequently diagnosed in horses age <6 months (19/38 cases). Short-term survival to hospital discharge for horses recovered from anaesthesia was 98% (55/56) with the most common post operative complications being diarrhoea and inappetance. Intra-abdominal adhesions were identified in 2/8 horses requiring a second celiotomy. Long-term follow-up was available for 45 horses and 87% (39/45) were alive at least 12 months after surgery. CONCLUSIONS: As previously reported, faecalith obstruction is a frequent surgical lesion in the miniature horse and is most common in miniature horses age <6 months. The incidence of adhesion formation may be lower than previously reported.

Gene-mediated restoration of cartilage matrix by combination insulin-like growth factor-I/interleukin-1 receptor antagonist therapy.

Combination of growth factor gene-enhanced cartilage matrix synthesis with interleukin-1 receptor antagonist protein (IL-1Ra) abrogation of cartilage matrix degradation may reduce and possibly reverse cartilage loss in synovitis and osteoarthritis. The feasibility of cotransduction of synovial membrane with two such genes that may act on cartilage homeostasis was investigated in an in vitro coculture system. Cultured synoviocytes in monolayer were cotransduced with E1-deleted adenoviral vectors, one containing IGF-I coding sequence under cytomegalovirus (CMV) promoter control (200 multiplicities of infection (moi)), and the second containing IL-1Ra sequence under CMV promoter control (100 moi). Adenovirus-IGF-I (AdIGF-I) transduction and AdIGF-I/AdIL-1Ra cotransduction of synovial monolayer cultures resulted in increased IGF-I mRNA and ligand expression, and similarly AdIL-1Ra and AdIGF-I/AdIL-1Ra-transduced cultures expressed high levels of IL-1Ra. Northern analysis confirmed a single mRNA transcript of the appropriate size for both IGF-I and IL-1Ra transgene expression. Synovial cell monolayer and cartilage explant coculture experiments were used to examine the effects of IGF-I and IL-1Ra protein expressed by transduced synoviocytes on normal and IL-1-depleted cartilage. Transduced monolayer cultures produced peak medium IGF-I content of 114+/-20.2 ng/ml and IL-1Ra levels of 241.8+/-10.5 ng/ml at 48 h after transduction. These IGF-I concentrations were sufficient to produce significantly increased proteoglycan (PG) content of normal cartilage cultured in medium conditioned by AdIGF-I and AdIGF-I/AdIL-1Ra-transduced synoviocytes. Interleukin-1-exposed cartilage was markedly depleted of PG, and this catabolic state was partially reversed in AdIGF-I-transduced cultures and fully reversed by AdIGF-I/AdIL-1Ra-transduced synovial cocultures. These data indicate that cultured synoviocytes are readily cotransduced by two recombinant adenoviral vectors containing transgenes active in restoring joint health. The AdIL-1Ra and AdIGF-I transgenes were abundantly expressed and the secreted products achieved therapeutic concentrations by day 2. The resulting increase in matrix biosynthesis returned cartilage PG content to normal levels. These data suggest that there may be significant value in cotransduction of synovial membrane to attenuate cartilage malacia associated with synovitis, injury, or early arthritis.

On the occurrence of coenospermia in mesothelid spiders (Araneae: Heptathelidae).

Two species of the early derivative spider family Heptathelidae (Heptathela kimurai yanbaruensis and Ryuthela nishihirai nishihirai) have been investigated with respect to spermiogenesis, focussing on late events during which peculiar transfer forms are developed. It is shown, for the first time in detail, that these spiders produce coenospermia. The coenospermia of these species are large aggregates containing more than 20 individual encapsulated spermatozoa. The coenospermia possess a likely flexible envelope formed by a thick multilayered secretion, which protects the spermatozoa during transfer to the female genital system and storage in the receptacula. In addition, a short description of the main cell components of the individual spermatozoa is given as a complement to previous studies. With the observation presented here, the suggestion that coenospermia are an ancestral character in the Araneae is further confirmed, and plesiomorphic features of spider sperms are consolidated.

Vagal and sympathetic influences on the ferret lower oesophageal sphincter.

This study has investigated the relative involvement of cholinergic, adrenergic, nitric oxide and tachykininergic transmission in extrinsic neural influences on the lower oesophageal sphincter (LOS) in urethane anaesthetized ferrets. A micromanometric assembly (OD 1.75 mm) incorporating a sleeve sensor was used for high-fidelity oesophageal, LOS and gastric pressure measurement at low perfusion rates (< 0.1 ml/min). The LOS response to vagal and splanchnic nerve stimulation (0.5 ms pulse width, 10 s duration) was frequency- and voltage-dependent. LOS responses to stimulation at 20 V, 10 Hz were investigated in separate groups of animals with either L-NAME (100 mg/kg), hexamethonium (15 mg/kg), guanethidine (5 mg/kg), CP96,345 (NK-1 antagonist, 4 mg/kg), atropine (0.4 mg/kg) or propranolol (1 mg/kg). Propranolol treatment was followed by yohimbine (1 mg/kg) and prazosin (0.25 mg/kg). Vagal stimulation caused an immediate decrease in LOS pressure, followed by increase on cessation of stimulation, followed by a prolonged decrease (77 +/- 2%) for up to 5 min. L-NAME did not affect inhibition, but increased excitation 4-fold (p < 0.001). Guanethidine and CP96,345 had no major effect. Hexamethonium decreased the inhibitory (p < 0.05) and excitatory (p < 0.01) responses. Atropine reduced the excitatory response (p < 0.05). Some inhibition still remained if all treatments were combined. Splanchnic stimulation reduced LOS pressure by 70 +/- 6% for 101 +/- 17 s. L-NAME, guanethidine, hexamethonium and CP96,345 all independently significantly reduced inhibition. The combination of guanethidine and CP96,345 usually abolished splanchnic-induced inhibition. Atropine was without effect. Propranolol (1 mg/kg) changed the splanchnic-induced response from mainly inhibition to excitation (100 +/- 44% increase). LOS responses to noradrenaline (1-10 micrograms close IA) showed similar features to responses to splanchnic stimulation. We conclude that vagal stimulation evokes LOS relaxation via activation of established cholinergic and NANC mechanisms and other, unidentified mechanisms. Splanchnic stimulation activates adrenergic neurones probably via nicotinic and non-nicotinic ganglionic mechanisms, which in turn elicit beta adrenergic inhibitory effects on the LOS. Splanchnic stimulation also antidromically activates spinal afferent fibres. These may release substance P from peripheral myenteric plexus and prevertebral ganglionic endings causing activation of myenteric NANC inhibitory neurones and sympathetic neurones, respectively.

Selection of medical students--a follow-up study.

The attributes of 1,026 medical students admitted to university on academic criteria and by interview between 1980 and 1983, and the characteristics of 822 of them who graduated between 1985 and 1988, were analysed. There were 133 students (13%) who failed and were excluded, 99 (10%) repeated 1 or more years of study, 67 (7%) voluntarily withdrew, 42 (4%) completed a B.Sc. degree during their medical training, and 675 graduated in the minimum time. The admitted and graduated students were mainly white (85%), male (67%) and had no academic experience other than matriculation (69%). During the review period the proportion of 'non-whites', women and applicants with university experience increased. Students who voluntarily withdrew had significantly low interview scores; applicants with university experience and applicants who subsequently failed had significantly high interview scores. It is concluded that the interview is useful, that the demographic characteristics of the classes are changing, and that traditional academic standards have been maintained.

Selection of medical students--effect on class composition of using non-academic criteria.

The attributes of 2,304 applicants for admission to the University of the Witwatersrand Medical School were analysed. Those measured by previous academic performance, biographical history and assessment at interview were significantly different. Inclusion of non-academic criteria in admission decisions broadens the personal attributes of the class, and alters the ethnic and gender composition, without affecting subsequent failure rate.

Moulting and morphogenesis of sensilla in a prostigmate mite (acari, actinotrichida, actinedida: caeculidae) I. Mechanoreceptive bristles.

In the prostigmate mite Microcaeculus steineri delamarei moulting and morphogenesis of mechanoreceptive sensilla were studied by electron microscopy and compared to corresponding sensilla of other arthropods. Dendritic contact with the cuticular parts of old sensilla breaks down during apolysis. Two groups of cells are engaged in the formation of new sensilla: 1) several trichogen and two tormogen cells in a semicircular arrangement, and 2) two sheath cells surrounding the mechanoreceptive dendrites. Cells ensheathing the dendrites do not play any part in the formation of bristles. These observations differ from those on insect sensilla during moulting.