Animal movement on the hoof and on the cart and its implications for understanding exchange within the Indus Civilisation.

Movement of resources was essential to the survival and success of early complex societies. The sources and destinations of goods and the means of transportation - be it by boats, carts and/or foot - can often be inferred, but the logistics of these movements are inherently more difficult to ascertain. Here, we use strontium isotopic analysis to test hypotheses about the role of animal and animal-powered transport in medium and long-distance movement and exchange, using the Indus Civilization as a case study. Across the wide geographical spread of the Indus Civilisation, there is strong evidence for long-distance exchange of raw materials and finished objects and this process is presumed to involve boats and animal-driven transport, although there is little evidence as to the relative importance of each mode of movement. Strontium isotopic analysis of animal remains from four sites analysed for this study combined with results from nine other sites indicates limited long-distance animal movement between different geological zones within the Indus Civilisation. These findings suggest that individual animals primarily moved short- or medium-distances, though there are several significant exceptions seen in some pigs and cattle found at two large urban sites. We infer that long-distance transport of goods, be it raw materials, finished objects, other goods, or the animals themselves, could have occurred through the use of boats and waterways, by traction animals moving over long distances that did not end up in the archaeological record, and/or by different animals participating in many short to medium-distance movements.

Effects of fat loss and low energy availability on the serum cardiometabolic profile of physique athletes.

Low energy availability (LEA) is a health concern for athletes, although it may paradoxically lead to improved cardiometabolic health in the general population. We investigated the associations between LEA, body composition, and serum cardiometabolic profile in 23 physique athletes (DIET) and 21 controls (CONT) during a 5-month pre-competition diet (MID), followed by 1 week of increased energy availability (COMP) and a 5-month weight regain period (POST). Quantification of 250 serum metabolome variables was conducted by NMR spectroscopy, body composition by dual-energy x-ray absorptiometry, dietary intake by food diaries, and exercise levels by training logs. Body fat percentage decreased from 19.5 ± 7.0% to 8.3 ± 5.3% (p < 0.001) in DIET through increased exercise levels and decreased energy intake, while CONT maintained those constant. In MID, DIET had increased (FDR < 0.01) HDL cholesterol, HDL particle size and number, and decreased (FDR < 0.05) VLDL lipids, serum triglycerides, and low-grade inflammation (glycoprotein acetyls) compared to baseline and CONT. The changes were associated with reduced android fat mass (-78 ± 13%) and energy intake (-28 ± 10%). In COMP, most of the metabolic changes found in MID persisted, except for altered triglycerides in all lipoprotein classes. After weight regain in POST, serum metabolome, body composition, energy intake, and exercise levels had reverted to baseline levels. In conclusion, fat loss and LEA may have beneficial yet transient effects on the serum cardiometabolic profile of lean individuals. Especially the HDL lipidome and lipoprotein triglycerides offer potential novel biomarkers for detecting LEA in athletes.

Comparison of mechanical properties and host tissue response to OviTex™ and Strattice™ surgical meshes.

PURPOSE: This study compared the in vitro/benchtop and in vivo mechanical properties and host biologic response to ovine rumen-derived/polymer mesh hybrid OviTex™ with porcine-derived acellular dermal matrix Strattice™ Firm. METHODS: OviTex 2S Resorbable (OviTex 2S-R) and Strattice morphology were examined in vitro using histology and scanning electron microscopy; mechanical properties were assessed via tensile test; in vivo host biologic response and explant mechanics were evaluated in a rodent subcutaneous model. Separately, OviTex 1S Permanent (OviTex 1S-P) and Strattice were evaluated in a primate abdominal wall repair model. RESULTS: OviTex 2S-R demonstrated layer separation, whereas Strattice retained its structural integrity and demonstrated higher maximum load than OviTex 2S-R out-of-package (124.8 ± 11.1 N/cm vs 37.9 ± 5.5 N/cm, p < 0.001), 24 h (55.7 ± 7.4 N/cm vs 5.6 ± 3.8 N/cm, p < 0.001), 48 h (45.3 ± 14.8 N/cm vs 2.8 ± 2.6 N/cm, p = 0.003), and 72 h (29.2 ± 10.5 N/cm vs 3.2 ± 3.1 N/cm, p = 0.006) following collagenase digestion. In rodents, inflammatory cell infiltration was observed between OviTex 2S-R layers, while Strattice induced a minimal inflammatory response. Strattice retained higher maximum load at 3 (46.3 ± 27.4 N/cm vs 9.5 ± 3.2 N/cm, p = 0.041) and 6 weeks (28.6 ± 14.1 N/cm vs 7.0 ± 3.0 N/cm, p = 0.029). In primates, OviTex 1S-P exhibited loss of composite mesh integrity whereas Strattice integrated into host tissue with minimal inflammation and retained higher maximum load at 1 month than OviTex 1S-P (66.8 ± 43.4 N/cm vs 9.6 ± 4.4 N/cm; p = 0.151). CONCLUSIONS: Strattice retained greater mechanical strength as shown by lower susceptibility to collagenase degradation than OviTex 2S-R in vitro, as well as higher maximum load and improved host biologic response than OviTex 2S-R in rodents and OviTex 1S-P in primates.

Taurine, an osteocyte metabolite, protects against oxidative stress-induced cell death and decreases inhibitors of the Wnt/ß-catenin signaling pathway.

Taurine has been shown to have positive effects on bone mass, which are thought to be due in part to its cytoprotective effects on osteoblasts and here we show that taurine also protects osteocytes against cell death due to reactive oxygen species. Using the IDG-SW3 cell line, the expression of the taurine uptake transporter Taut/Slc6a6 is increased during osteoblast to osteocyte differentiation. Taurine had no effect on genes associated with osteoblast to osteocyte differentiation such as Dmp1, Phex or osteocalcin, even at high doses, but a slight yet significant inhibition of alkaline phosphatase was observed at the highest dose (50 mM). No effect was seen on the osteoclast regulatory genes Rankl and Opg, however the wnt antagonist Sost/sclerostin was potently and dose-dependently downregulated in response to taurine supplementation. Taurine also significantly inhibited Dkk1 mRNA expression, but only at 50 mM. Interestingly, osteocytes were found to also be able to synthesize taurine intracellularly, potentially as a self-protective mechanism, but do not secrete the metabolite. A highly significant increase in the expression of cysteine dioxygenase (Cdo), a key enzyme necessary for the production of taurine, was observed with osteoblast to osteocyte differentiation along with a decrease in methionine, the precursor of taurine. For the first time, we describe the synthesis of taurine by osteocytes, potentially to preserve viability and to regulate bone formation through inhibition of sclerostin.

A visible-light photocatalytic thiolation of aryl, heteroaryl and vinyl iodides.

The general catalytic synthesis of aryl and vinyl thioethers from readily available halides remains a challenge. Herein we report a unified method for the thiolation of aryl and vinyl iodides with dialkyl disulfides using visible light photoredox catalysis. A range of thioether products bearing diverse functional groups can be accessed in high yield and with excellent chemoselectivity. We demonstrate the versatility of this method through the expedient synthesis of a family of thioether-rich natural products. A detailed investigation of the photocatalytic mechanism is presented from both steady-state and time-resolved luminescent quenching as well as transient absorption spectroscopy experiments.

Beam-Target Helicity Asymmetry for γ[over →]n[over →]→π

We report the first beam-target double-polarization asymmetries in the γ+n(p)→π^{-}+p(p) reaction spanning the nucleon resonance region from invariant mass W=1500 to 2300 MeV. Circularly polarized photons and longitudinally polarized deuterons in solid hydrogen deuteride (HD) have been used with the CEBAF Large Acceptance Spectrometer (CLAS) at Jefferson Lab. The exclusive final state has been extracted using three very different analyses that show excellent agreement, and these have been used to deduce the E polarization observable for an effective neutron target. These results have been incorporated into new partial wave analyses and have led to significant revisions for several γnN^{*} resonance photocouplings.

'Trophic' and 'source' amino acids in trophic estimation: a likely metabolic explanation.

Amino acid nitrogen isotopic analysis is a relatively new method for estimating trophic position. It uses the isotopic difference between an individual's 'trophic' and 'source' amino acids to determine its trophic position. So far, there is no accepted explanation for the mechanism by which the isotopic signals in 'trophic' and 'source' amino acids arise. Yet without a metabolic understanding, the utility of nitrogen isotopic analyses as a method for probing trophic relations, at either bulk tissue or amino acid level, is limited. I draw on isotopic tracer studies of protein metabolism, together with a consideration of amino acid metabolic pathways, to suggest that the 'trophic'/'source' groupings have a fundamental metabolic origin, to do with the cycling of amino-nitrogen between amino acids. 'Trophic' amino acids are those whose amino-nitrogens are interchangeable, part of a metabolic amino-nitrogen pool, and 'source' amino acids are those whose amino-nitrogens are not interchangeable with the metabolic pool. Nitrogen isotopic values of 'trophic' amino acids will reflect an averaged isotopic signal of all such dietary amino acids, offset by the integrated effect of isotopic fractionation from nitrogen cycling, and modulated by metabolic and physiological effects. Isotopic values of 'source' amino acids will be more closely linked to those of equivalent dietary amino acids, but also modulated by metabolism and physiology. The complexity of nitrogen cycling suggests that a single identifiable value for 'trophic discrimination factors' is unlikely to exist. Greater consideration of physiology and metabolism should help in better understanding observed patterns in nitrogen isotopic values.

High pitch, low voltage dual source CT pulmonary angiography: assessment of image quality and diagnostic acceptability with hybrid iterative reconstruction.

Increased use of CT Pulmonary angiography in suspected pulmonary embolism (PE) has driven research to minimize radiation dose while maintaining image quality and diagnostic accuracy. Following institutional review board approval, we performed a retrospective comparison study in patients with suspected PE. Patients were scanned using an ultra high pitch dual source technique (pitch = 2.6) using 120 kV (SVCTPA) (n = 54) or 100 kV (RV-CTPA) (n = 52). SV-CTPA images were reconstructed using filtered back projection (SV-wFBP) and RV-CTPA images were reconstructed using both FBP (RV-wFBP) and Iterative Reconstruction (RV-IR). Comparison of radiation dose, diagnostic ability, subjective image noise, quality, and sharpness, diagnostic agreement, signal to noise (SNR) and contrast to noise ratios (CNR) were performed. Mean effective dose was 2.56 ± 0.19 mSv for the RV protocol compared to 5.36 ± 0.60 mSv for the SV. The RV-CTPA protocol resulted in a mean DLP reduction of 52 % and mean CTDI reduction of 51 %. Pulmonary artery SNR and CNR were significantly higher on RV-IR images than SV-wFBP (p = 0.007, p = 0.003). Mean subjective image noise, quality and sharpness scores did not differ significantly between the SV-wFBP and RVIR images (p > 0.05). Subjective quality scores were significantly better for the RV-IR group compared to the RV-wFBP group (p < 0.001). Agreement between readers for presence or absence of pulmonary emboli on RV-IR images was almost perfect (κ = 0.891, p < 0.001). Iterative reconstruction complements ultra high pitch dual source CTPA examinations acquired using a reduced voltage resulting in higher mean pulmonary artery SNR and CNR when compared to both RV-wFBP and SV-CTPA.

Water consumption in Iron Age, Roman, and Early Medieval Croatia.

Patterns of water consumption by past human populations are rarely considered, yet drinking behavior is socially mediated and access to water sources is often socially controlled. Oxygen isotope analysis of archeological human remains is commonly used to identify migrants in the archeological record, but it can also be used to consider water itself, as this technique documents water consumption rather than migration directly. Here, we report an oxygen isotope study of humans and animals from coastal regions of Croatia in the Iron Age, Roman, and Early Medieval periods. The results show that while faunal values have little diachronic variation, the human data vary through time, and there are wide ranges of values within each period. Our interpretation is that this is not solely a result of mobility, but that human behavior can and did lead to human oxygen isotope ratios that are different from that expected from consumption of local precipitation.

Delivery validation of an automated modulated electron radiotherapy plan.

PURPOSE: Modulated electron radiation therapy (MERT) represents an active area of interest that offers the potential to improve healthy tissue sparing in treatment of certain cancer cases. Challenges remain however in accurate beamlet dose calculation, plan optimization, collimation method, and delivery accuracy. In this work, the authors investigate the accuracy and efficiency of an end-to-end MERT plan and automated delivery method. METHODS: Treatment planning was initiated on a previously treated whole breast irradiation case including an electron boost. All dose calculations were performed using Monte Carlo methods and beam weights were determined using a research-based treatment planning system capable of inverse optimization. The plan was delivered to radiochromic film placed in a water equivalent phantom for verification, using an automated motorized tertiary collimator. RESULTS: The automated delivery, which covered four electron energies, 196 subfields, and 6183 total MU was completed in 25.8 min, including 6.2 min of beam-on time. The remainder of the delivery time was spent on collimator leaf motion and the automated interfacing with the accelerator in service mode. Comparison of the planned and delivered film dose gave 3%/3mm gamma pass rates of 62.1%, 99.8%, 97.8%, 98.3%, and 98.7% for the 9, 12, 16, and 20 MeV, and combined energy deliveries, respectively. Delivery was also performed with a MapCHECK device and resulted in 3%/3 mm gamma pass rates of 88.8%, 86.1%, 89.4%, and 94.8% for the 9, 12, 16, and 20 MeV energies, respectively. CONCLUSIONS: Results of the authors' study showed that an accurate delivery utilizing an add-on tertiary electron collimator is possible using Monte Carlo calculated plans and inverse optimization, which brings MERT closer to becoming a viable option for physicians in treating superficial malignancies.

Design and validation of novel scattering foils for modulated electron radiation therapy.

Modulated Electron Radiation Therapy (MERT) continues to be an area of interest to various groups, however, the scattering foils used in beam flattening have not been optimized for this modality. In this work, the feasibility of novel scattering foils specifically designed for MERT is investigated using Monte Carlo methods. Different designs based on foil material, shape and thickness were analyzed. It was shown that low atomic number materials such as aluminum were optimal, while shaped foils such as those employed in current dual foil designs were not necessary. Aluminum foil thickness between 0.36 mm and 1.50 mm were capable of sufficiently broadening beams with energies between 12 MeV and 20 MeV respectively, with beams of lower energies receiving sufficient scatter from the treatment head components and air scatter. Finally, custom foils were manufactured based upon previously simulated designs and were placed into the beamline of a 2100 EX accelerator, and showed excellent agreement between the simulated and measured PDDs and profiles. Custom foils achieved higher dose rates on the central axis compared to the clinical foils by factors of 5.4, 4.9 and 4.5 for 12 MeV, 16 MeV and 20 MeV, respectively.

Review of Irish Civil Service sickness absence referrals 2008-10.

BACKGROUND: Long-term sickness absence can have negative consequences for individuals and for their employers. Occupational health has an important role in assisting workplace rehabilitation in such cases. AIMS: To investigate long-term sickness absence referrals in the Irish Civil Service in terms of epidemiological profile, illness categories and eventual outcomes. METHODS: A retrospective review of consecutive new long-term sickness absence cases referred between January 2008 and April 2008 and followed up to July 2010, using review of electronic and paper medical records and personnel department data to establish case outcomes. RESULTS: Three hundred and one cases were available for analysis. There were more long-term sickness absence cases among older employees, with female employees and clerical officer grades more likely to be referred. The principal diagnostic groups were mental health issues (30%), musculoskeletal disorders (13%) and cancer (11%). The eventual outcomes were the following: return to work (83%) and ill-health retirement (8%); 2% were still on sick leave and the remaining 7% had left civil service employment for other reasons at the end of the study period. CONCLUSIONS: The final outcome in a large majority of case referrals was to resume work, with only a small proportion retiring on ill-health grounds. Mental health disorders, musculoskeletal disorders and cancers were the principal reasons for absence.

Interleukin-17-dependent CXCL13 mediates mucosal vaccine-induced immunity against tuberculosis.

The variable efficacy of tuberculosis (TB) vaccines and the emergence of drug-resistant strains of Mycobacterium tuberculosis (Mtb) emphasize the urgency for not only generating new and more effective vaccines against TB but also understanding the underlying mechanisms that mediate vaccine-induced protection. We demonstrate that mucosal adjuvants, such as type II heat labile enterotoxin (LT-IIb), delivered through the mucosal route induce pulmonary Mtb-specific T helper type 17 (Th17) responses and provide vaccine-induced protection against Mtb infection. Importantly, protection is interferon-γ (IFNγ)-independent but interleukin-17 (IL-17)-dependent. Our data show that IL-17 mediates C-X-C motif chemokine ligand 13 (CXCL13) induction in the lung for strategic localization of proinflammatory cytokine-producing CXCR5+ (C-X-C motif chemokine receptor 5-positive) T cells within lymphoid structures, thereby promoting early and efficient macrophage activation and the control of Mtb. Our studies highlight the potential value of targeting the IL-17-CXCL13 pathway rather than the IFNγ pathway as a new strategy to improve mucosal vaccines against TB.

The diet-body offset in human nitrogen isotopic values: a controlled dietary study.

The "trophic level enrichment" between diet and body results in an overall increase in nitrogen isotopic values as the food chain is ascended. Quantifying the diet-body Δ(15) N spacing has proved difficult, particularly for humans. The value is usually assumed to be +3-5‰ in the archaeological literature. We report here the first (to our knowledge) data from humans on isotopically known diets, comparing dietary intake and a body tissue sample, that of red blood cells. Samples were taken from 11 subjects on controlled diets for a 30-day period, where the controlled diets were designed to match each individual's habitual diet, thus reducing problems with short-term changes in diet causing isotopic changes in the body pool. The Δ(15) N(diet-RBC) was measured as +3.5‰. Using measured offsets from other studies, we estimate the human Δ(15) N(diet-keratin) as +5.0-5.3‰, which is in good agreement with values derived from the two other studies using individual diet records. We also estimate a value for Δ(15) N(diet-collagen) of ≈6‰, again in combination with measured offsets from other studies. This value is larger than usually assumed in palaeodietary studies, which suggests that the proportion of animal protein in prehistoric human diet may have often been overestimated in isotopic studies of palaeodiet.

Novel iron-regulated and Fur-regulated small regulatory RNAs in Aggregatibacter actinomycetemcomitans.

Iron can regulate biofilm formation via non-coding small RNA (sRNA). To determine if iron-regulated sRNAs are involved in biofilm formation by the periodontopathogen Aggregatibacter actinomycetemcomitans, total RNA was isolated from bacteria cultured with iron supplementation or chelation. Transcriptional analysis demonstrated that the expression of four sRNA molecules (JA01-JA04) identified by bioinformatics was significantly upregulated in iron-limited medium compared with iron-rich medium. A DNA fragment encoding each sRNA promoter was able to titrate Escherichia coli ferric uptake regulator (Fur) from a Fur-repressible reporter fusion in an iron uptake regulator titration assay. Cell lysates containing recombinant AaFur shifted the mobility of sRNA-specific DNAs in a gel shift assay. Potential targets of these sRNAs, determined in silico, included genes involved in biofilm formation. The A. actinomycetemcomitans overexpressing JA03 sRNA maintained a rough phenotype on agar, but no longer adhered to uncoated polystyrene or glass, although biofilm determinant gene expression was only modestly decreased. In summary, these sRNAs have the ability to modulate biofilm formation, but their functional target genes remain to be confirmed.

An experimental feasibility study on the use of scattering foil free beams for modulated electron radiotherapy.

The potential benefit of using scattering foil free beams for delivery of modulated electron radiotherapy is investigated in this work. Removal of the scattering foil from the beamline showed a measured bremsstrahlung tail dose reduction just beyond R(p) by a factor of 12.2, 6.9, 7.4, 7.4 and 8.3 for 6, 9, 12, 16 and 20 MeV beams respectively for 2 × 2 cm(2) fields defined on-axis when compared to the clinical beamline. Monte Carlo simulations were matched to measured data through careful tuning of source parameters and the modification of certain accelerator components beyond the manufacturer's specifications. An accelerator model based on the clinical beamline and one with the scattering foil removed were imported into a Monte Carlo-based treatment planning system (McGill Monte Carlo Treatment Planning). A treatment planning study was conducted on a test phantom consisting of a PTV and two distal organs at risk (OAR) by comparing a plan using the clinical beamline to a plan using a scattering foil free beamline. A DVH comparison revealed that for quasi-identical target coverage, the volume of each OAR receiving a given dose was reduced, thus reducing the dose deposited in healthy tissue.

Changing cultures, changing cuisines: Cultural transitions and dietary change in Iron Age, Roman, and Early Medieval Croatia.

Food is well-known to encode social and cultural values, for example different social groups use different consumption patterns to act as social boundaries. When societies and cultures change, whether through drift, through population replacement or other factors, diet may also alter despite unchanging resource availability within a region. This study investigates the extent to which dietary change coincides with cultural change, to understand the effects of large-scale migrations on the populations' diets. Through stable carbon and nitrogen isotope analysis of Iron Age, Roman, and Early Medieval human bone collagen, we show that in Croatia large-scale cultural change led to significant changes in diet. The isotopic evidence indicates that Iron Age diet consisted of C(3) foodstuffs with no isotopic evidence for the consumption of C(4) or marine resources. With the Roman conquest, marine resources were added to the diet, although C(3) foodstuffs continued to play an important role. In the Early Medieval period, this marine component was lost and varying amounts of C(4) foodstuffs, probably millet, were added to the otherwise C(3) diet. In both of these transitions it is likely that the changes in diet are related to the arrival of a new people into the area.