Laser Excitation of the

LiSrAlF_{6} crystals doped with ^{229}Th are used in a laser-based search for the nuclear isomeric transition. Two spectroscopic features near the nuclear transition energy are observed. The first is a broad excitation feature that produces redshifted fluorescence that decays with a timescale of a few seconds. The second is a narrow, laser-linewidth-limited spectral feature at 148.382 19(4)_{stat}(20)_{sys} nm [2020 407.3(5)_{stat}(30)_{sys} GHz] that decays with a lifetime of 568(13)_{stat}(20)_{sys} s. This feature is assigned to the excitation of the ^{229}Th nuclear isomeric state, whose energy is found to be 8.355 733(2)_{stat}(10)_{sys} eV in ^{229}Th:LiSrAlF_{6}.

Atomic Ionization by Scalar Dark Matter and Solar Scalars.

We calculate the cross sections of atomic ionization by absorption of scalar particles in the energy range from a few eV to 100 keV. We consider both nonrelativistic particles (dark matter candidates) and relativistic particles that may be produced inside the Sun. We provide numerical results for atoms relevant for direct dark matter searches (O, Na, Ar, Ca, Ge, I, Xe, W and Tl). We identify a crucial flaw in previous calculations and show that they overestimated the ionization cross sections by several orders of magnitude due to violation of the orthogonality of the bound and continuum electron wave functions. Using our computed cross sections, we interpret the recent data from the Xenon1T experiment, establishing the first direct bounds on coupling of scalars to electrons. We argue that the Xenon1T excess can be explained by the emission of scalars from the Sun. Although our finding is in a similar tension with astrophysical bounds as the solar axion hypothesis, we establish direct limits on scalar DM for the ∼1-10 keV mass range. We also update axio-ionization cross sections. Numerical data files are provided.

Regulation of Angiogenesis Discriminates Tissue Resident MSCs from Effective and Defective Osteogenic Environments.

BACKGROUND: The biological mechanisms that contribute to atrophic long bone non-union are poorly understood. Multipotential mesenchymal stromal cells (MSCs) are key contributors to bone formation and are recognised as important mediators of blood vessel formation. This study examines the role of MSCs in tissue formation at the site of atrophic non-union. MATERIALS AND METHODS: Tissue and MSCs from non-union sites (n = 20) and induced periosteal (IP) membrane formed following the Masquelet bone reconstruction technique (n = 15) or bone marrow (n = 8) were compared. MSC content, differentiation, and influence on angiogenesis were measured in vitro. Cell content and vasculature measurements were performed by flow cytometry and histology, and gene expression was measured by quantitative polymerase chain reaction (qPCR). RESULTS: MSCs from non-union sites had comparable differentiation potential to bone marrow MSCs. Compared with induced periosteum, non-union tissue contained similar proportion of colony-forming cells, but a greater proportion of pericytes (p = 0.036), and endothelial cells (p = 0.016) and blood vessels were more numerous (p = 0.001) with smaller luminal diameter (p = 0.046). MSCs showed marked differences in angiogenic transcripts depending on the source, and those from induced periosteum, but not non-union tissue, inhibited early stages of in vitro angiogenesis. CONCLUSIONS: In vitro, non-union site derived MSCs have no impairment of differentiation capacity, but they differ from IP-derived MSCs in mediating angiogenesis. Local MSCs may thus be strongly implicated in the formation of the immature vascular network at the non-union site. Attention should be given to their angiogenic support profile when selecting MSCs for regenerative therapy.

Transport paths and vertical exchange characteristics of haze pollution in Southern China.

Transport paths and vertical exchange characteristics are important factors for understanding the long-term transport, dispersion capability for haze prediction. Many previous studies revealed that the Pearl River Delta (PRD) region, one of the major polluted areas in China, is largely affected by the long-range pollution transport. However, mostly of these studies focused on the source apportionment or horizontal transport path of pollutants by using short-term data, and the vertical exchange characteristics had been rarely analyzed. In this study, using HYSPLIT model, the transport paths and the vertical exchange characteristics of haze episodes over four sub-region of Guangdong (GD) Province in southern China of dry season and wet season were analyzed by using 10years data from 2005 to 2014. Three major transport paths can be statistically summarized based on the long-term data. The haze episodes in PRD and North-GD were distinguished by the characteristics of high frequency and long duration, while the West-GD and East-GD are relatively clean. The haze over North-GD and PRD were mainly influenced by the airflows from northern path, which could bring the pollution from Jiangxi, Anhui, and also influenced by the airflows from coastal path, which could bring the pollution of eastern coastal from Zhejiang and Fujian to Guangdong, while regional transport contributions from Guangdong province and adjacent areas can also be clearly observed. The haze pollution from the identified two major transport paths were mainly transported within the mixing layer (>80% trajectories, <500m), whereas the probability of haze trajectories across mixing layer was relatively low and generally associated with much longer transport distance and higher terrain height over Western China. Combing the vertical exchange analysis, results also show that Wuyi Mountains and Nanling Mountains played a role as barrier to obstruct the haze airflows from other regions of China to the Guangdong province.

Methodological quality assessment of paper-based systematic reviews published in oral health.

OBJECTIVES: This study aimed to conduct a methodological assessment of paper-based systematic reviews (SR) published in oral health using a validated checklist. A secondary objective was to explore temporal trends on methodological quality. MATERIAL AND METHODS: Two electronic databases (OVID Medline and OVID EMBASE) were searched for paper-based SR of interventions published in oral health from inception to October 2014. Manual searches of the reference lists of paper-based SR were also conducted. Methodological quality of included paper-based SR was assessed using an 11-item questionnaire, Assessment of Multiple Systematic Reviews (AMSTAR) checklist. Methodological quality was summarized using the median and inter-quartile range (IQR) of the AMSTAR score over different categories and time periods. RESULTS: A total of 643 paper-based SR were included. The overall median AMSTAR score was 4 (IQR 2-6). The highest median score (5) was found in the pain dentistry and periodontology fields, while the lowest median score (3) was found in implant dentistry, restorative dentistry, oral medicine, and prosthodontics. The number of paper-based SR per year and the median AMSTAR score increased over time (median score in 1990s was 2 (IQR 2-3), 2000s was 4 (IQR 2-5), and 2010 onwards was 5 (IQR 3-6)). CONCLUSION: Although the methodological quality of paper-based SR published in oral health has improved in the last few years, there is still scope for improving quality in most evaluated dental specialties. CLINICAL RELEVANCE: Large-scale assessment of methodological quality of dental SR highlights areas of methodological strengths and weaknesses that can be targeted in future publications to encourage better quality review methodology.

ACE gene sequence and nucleotide variants in IgA nephropathy.

INTRODUCTION: Association studies with single nucleotide polymorphisms (SNPs) have been contradictory. Haplotypes may be more helpful. With gene sequencing, all SNPs can be found for construction of haplotypes. METHODS: The ACE gene was sequenced in four healthy Chinese subjects and 20 patients with IgA nephropathy (IgAN) to observe if differences exist among SNPs and haplotypes. 20 patients on angiotensin 1-converting enzyme inhibitor/angiotensin receptor antagonist (ACEI/ATRA) therapy were then compared with another 20 patients not treated with ACEI /ATRA to determine their renal outcome in response to ACEI/ATRA therapy and whether their genetic profile of ACE gene could play a role in determining their outcome to ACEI /ATRA therapy and progression to end-stage renal failure (ESRF). RESULTS: IgAN patients had 53 variants, of which 17 were unique, whereas normal subjects had 38 variants, of which two were unique (p less than 0.005). No unique variant was a significant risk factor for IgAN. Significant genotype and allele frequency differences in five variants were observed between IgAN patients with renal impairment and those with ESRF (p less than 0.02). CONCLUSION: Our data suggests that at least in the ACE gene, haplotyping SNPs within a single gene seems to have no added advantage over genotyping the individual component SNPs. The D allele and haplotype 3 confer an adverse prognosis, while the I allele and haplotype 5 appear to be renoprotective. The data suggests that genotypes of the ACE gene are linked to certain haplotypes, which could influence IgAN patients' response to ACEI/ATRA therapy.

Thermogravimetric investigation on co-combustion characteristics of tobacco residue and high-ash anthracite coal.

The thermal behavior of high-ash anthracite coal, tobacco residue and their blends during combustion processes was investigated by means of thermogravimetric analysis (20 K min(-1), ranging from ambient temperature to 1273 K). Effects of the mixed proportion between coal and tobacco residue on the combustion process, ignition and burnout characteristics were also studied. The results indicated that the combustion of tobacco residue was controlled by the emission of volatile matter; the regions were more complex for tobacco residue (four peaks) than for coal (two peaks). Also, the blends had integrative thermal profiles that reflected both tobacco residue and coal. The incorporation of tobacco residue could improve the combustion characteristics of high-ash anthracite coal, especially the ignition and burnout characteristics comparing with the separate burning of tobacco residue and coal. It was feasible to use the co-combustion of tobacco residue and high-ash anthracite coal as fuel.

The systemic inflammatory response following femoral canal reaming using the reamer-irrigator-aspirator (RIA) device.

We evaluated the peripheral release of inflammatory mediators after femoral fracture and subsequent intramedullary reaming using the RIA reamers. IL-6 was elevated after trauma, and reaming with RIA induced a measurable second hit response. However, despite a higher ISS, the levels of IL-6 in the RIA group were similar to the levels measured in a group of patients where reaming of the femoral canal was performed using conventional reamers. There was one death related to fat embolism syndrome in the conventional reamers group. However, the overall incidence of complications was low and similar between the 2 groups of studied patients. In polytrauma patients, large scale studies are desirable to evaluate further the immuno-inflammatory response using the RIA reamers prior to the instrumentation of the femoral canal.

Protective effects of FR167653 on chronic allograft nephropathy by inhibiting p38 MAPK in rats.

BACKGROUND: Chronic allograft nephropathy (CAN) remains a challenge for transplant clinicians. Some novel intervention strategies may shed new light on its treatment. METHODS: An orthotopic kidney transplant model in Fisher-to-Lewis rats was used with administration of cyclosporine alone or in combination with FR167653 (30 mg/kg/d subcuntaneously) to recipients. We analyzed renal function and urinary protein excretion. Animals were sacrificed at 30 weeks posttransplantation for histological and immunohistochemical studies. RESULTS: Renal function among vehicle-treated rats deteriorated progressively with substantial proteinuria compared with FR167653-treated rats. FR167653 administration significantly prevented the morphlogical features of CAN and prolonged rat survivals. p38 mitogen-activated protein kinase (MAPK) expression was markedly reduced by FR167653 treatment. Meanwhile, transforming growth factor-beta1 and monocyte chemotactic protein-1 expression were significantly down-regulated among FR167653-treated hosts. CONCLUSION: p38 MAPK phosphorylation correlated with CAN progression and inhibition of p38 MAPK by FR167653 may provide a potent novel therapeutic target for its prevention.

High dose Losartan and ACE gene polymorphism in IgA nephritis.

Background/aims Several studies have reported varying results of the influence of ACE gene on ACEI/ARB therapy. The efficacy of high dose ARB and its influence on ACE gene have not been explored. This is a 6 year randomised trial in IgA nephritis comparing high dose ARB (Losartan 200 mg/day) with normal dose ARB (Losartan 100 mg/day), normal dose ACEI (20 mg/day) and low dose ACEI (10 mg/day). Results Patients on high dose ARB had significantly lower proteinuria, 1.0 +/- 0.8 gm/day compared to 1.7 +/- 1.0 g/day in the other groups (P = 0.0005). The loss in eGFR was 0.7 ml min(-1)year(-1) for high dose ARB compared to 3.2-3.5 ml min(-1)year(-1) for the other three groups (P = 0.0005). There were more patients on high dose ARB with improvement in eGFR compared to other three groups (P < 0.001). Comparing patients with the three ACE genotypes DD, ID and II, all three groups responded well to therapy with decrease in proteinuria (P < 0.002). Only those on low dose ACEI (10 mg/day) with the I allele had increased in ESRF (P = 0.037). Conclusion High dose ARB is more efficacious in reducing proteinuria and preserving renal function when compared with normal dose ARB and ACEI, and also obviates the genomic influence of ACE gene polymorphism on renal survival.

Application of variable life adjusted display (VLAD) in early detection of deficiency in trauma care.

Early detection of deficient care is an increasingly important element of trauma audit. We aimed to assess the feasibility and demonstrate the use of a variable life adjusted display (VLAD) in trauma audit. Data from the Trauma Audit and Research Network database of Sheffield Teaching Hospitals NHS Trust were used to create a VLAD. A cumulative display of survival was plotted in which survivors were incorporated as a positive value equal to 1 minus the probability of survival, and deaths were incorporated as a negative value equal to the probability of survival. Downward deflections of the display thus indicated potentially deficient trauma care. Data from 191 consecutive patients over 1 year were plotted and displayed. The first 2 months of this period were characterised by a downward trend in the line, which may indicate suboptimum performance and provides an example of a trend that would prompt detailed review. The VLAD chart is a potentially useful "early warning" system for poor performance in trauma care. Further work should to be carried out to evaluate VLAD prospectively as an audit tool, perhaps involving comparison of VLAD charts from different institutions.

Improvement in initial survival of spinal injuries: a 10-year audit.

A 10-year retrospective study of all spinal injuries presenting to the Leeds Teaching Hospitals between 1991 and 2001. The hospitals provide secondary care to a population of 750,000 and tertiary care to a population of 2-3 million. In total 1119 spinal injuries were studied. The overall survival rate was 89%. The commonest age group for presentation was 25-29 years with a secondary peak in the seventh decade, a mean overall of 43 years. 66% of injuries occurred in males. The commonest cause was a fall from a height (44%), with road traffic accidents (RTA) causing 43%. Pedestrians were most at risk within the road traffic group, making up 63% of cases. Isolated cervical spine injuries made up 37% of all cases. Cervical fractures were most associated with neurological injury (50%). Immediate survival has increased over the decade from 83% in 1991 to 93% in 2001. The probability of survival was significant at P = 0.006 and actual survival at P = 0.012 (Pearson correlation). The causal analysis has not been carried out but it is thought likely that improved quality of care is responsible.

Incidence and causes of mortality following acute orthopaedic and trauma admissions.

PURPOSE: To analyse the incidence and causes of mortality of orthopaedic and trauma patients. METHODS: Between March 1995 and October 2000, there were 594 (404 females) in-patient deaths (2.8%) with a mean age of 82.14 years (range, 21-102 years) out of 21,122 acute admissions. The cause of death and details of the acute episode were collected from the hospital records, death certificates and postmortem examinations. Data collected were computerised and analysed using the Astute statistical package, University of Leeds. RESULTS: The most common primary diagnosis on admission was fracture neck of femur 392 (69.1%; P = 0.001). In total, 443 (78.1%) patients underwent surgical intervention of their injuries prior to mortality with 21 patients (4.7%) dying on the same day of the operation. The mean number of days between the initial surgical intervention and death was 22.3 days (range, 0-154 days). Of the patients who were treated non-operatively, 124 died due to poor medical condition (4 [3.2%] died within 24 h, 66 [51.6%] died within the first week and the rest died thereafter). In the death certificate, the most common primary cause of death recorded in the group of patients of 64 years of age and below was cancer followed by multi-organ failure. In the age group of 65 years and above, the most common primary cause of mortality was pneumonia followed by heart failure and myocardial infarction. CONCLUSIONS: In orthopaedic and trauma patients below the age of 65 years, the most common cause of death appears to be cancer followed by multiple system organ failure; in the elderly, pneumonia predominates followed by heart failure and myocardial infarction. Proximal femoral fractures accounted for 70% of the deaths.

ACE gene polymorphism and disease progression of IgA nephropathy in Asians in Singapore.

The deletion polymorphism of the angiotensin-converting enzyme (ACE) gene has been considered as a risk factor for IgA nephropathy and for its progression to end-stage renal failure. However, results from various studies are conflicting. We had genotyped the ACE gene in 100 patients with IgA nephropathy, 32 of whom were in end-stage renal failure and in 90 normal adult subjects. All DD cases were subjected to confirmation with a second PCR, performed with the insert-specific forward primer. Similar genotype frequencies were obtained for the 90 normal control subjects (II: 47%, ID: 44%, DD: 9%); for the 68 patients not in end-stage renal failure (ESRF) (II: 47%, ID: 46%, DD: 7%) and for the 32 patients with ESRF (II: 53%, ID: 38%, DD: 9%). The genotype frequencies in all 3 series are in Hardy-Weinberg equilibrium. These results suggest that ACE gene polymorphism is not a risk factor for IgA nephropathy and is not a predictor for its progression. Definitive proof of association between ACE gene polymorphism and progression in IgA nephropathy will require a prospective study, controlled for important risk factors, with adequate patient numbers and facility for confirming DD genotypes.

Kinetic analysis of the coding properties of O6-methylguanine in DNA: the crucial role of the conformation of the phosphodiester bond.

Production by N-nitroso compounds of O6-alkylguanine (O6-alkylG) in DNA directs the misincorporation of thymine during DNA replication, leading to G:C to A:T transition mutations, despite the fact that DNA containing O6-alkylG:T base pairs is less stable than that containing O6-alkylG:C pairs. We have examined the kinetics of incorporation by Klenow fragment (KF) of Escherichia coli DNA polymerase I of thymine (T) and of cytosine (C) opposite O6-MeG in the template DNA strand. Both T and C were incorporated opposite O6-MeG much slower than nucleotides forming regular A:T or G:C base pairs. Using various concentrations of dTTP, dCTP, or their phosphorothioate (Sp)-dNTP alpha S analogues, or a mixture of dTTP and dCTP, the progress of incorporation of a single nucleotide in a single catalytic cycle of a preformed KF-DNA complex was measured (pre-steady-state kinetics). The results were consistent with the kinetic scheme (Kuchta, R. D., Benkovic, P., & Benkovic, S. J. (1988) Biochemistry 27, 6716-6725): (1) binding of dNTP to polymerase-DNA; (2) conformational change in polymerase; (3) formation of phosphodiester between the dNTP and the 3'-OH of the primer; (4) conformational change of polymerase; (5) release of pyrophosphate. The results were analyzed mathematically to identify the steps at which the rate constants differ significantly between the incorporation of T and C. The only significant difference was the 5-fold difference in the rates of formation of the phosphodiester bond (for dTTP, kforward = 3.9 s-1 and kback = 1.9 s-1; for dCTP, kforward = 0.7 s-1 and kback = 0.9 s-1). These pre-steady-state progress curves were biphasic with a rapid initial burst followed by an apparently steady-state rise. Deconvolution of these curves gave direct evidence for the importance of the conformational change after polymerization by showing that the curves represented the sum of the rapid accumulation of the product of step 3 followed by the slow conversion of that to the product of step 5 (because of the rapidity of the release of pyrophosphate there was no significant accumulation of the product of step 4). The equilibrium constants for each step suggest that the greatest change in the Gibbs free energy occurs at the conformational change after polymerization and that while the formation of the phosphodiester bond to T is slightly exothermic, that to C is slightly endothermic.(ABSTRACT TRUNCATED AT 400 WORDS)