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The speciation of volatile organic compounds (VOCs) emitted from personal care products (PCPs) is complex and contributes to poor air quality and health risks to users via the inhalation exposure pathway. Detailed VOC emission profiles were generated for 26 sunscreen products; consequently, variability was observed between products, even though they were all designed for the same purpose. Some were found to contain fragrance compounds not labelled on their ingredients list. Five contaminant VOCs were identified (benzene, toluene, ethylbenzene, o-xylene, and p-xylene); headspace sampling of an additional 18 randomly selected products indicated that ethanol originating from fossil petroleum was a potential source. The gas phase emission rates of the VOCs were quantified for 15 of the most commonly emitted species using SIFT-MS. A wide range of emission rates were observed between the products. Usage estimates were made based on the recommended dose per body surface area, for which the total mass of VOCs emitted from one full-body application dose was in the range of 1.49 × 103–4.52 × 103 mg and 1.35 × 102–4.11 × 102 mg for facial application (men aged 16+; children aged 2–4). Depending on age and sex, an estimated 9.8–30 mg of ethanol is inhaled from one facial application of sunscreen.

An increasing fraction of volatile organic compounds (VOC) emissions come from the domestic use of solvents, contained within myriad commonplace consumer products. Emission rates are often poorly characterized and depend significantly on individual behavior and specific product formulation and usage. Time-concentration profiles of volatile organic compounds (VOCs) arising from the use of a representative selection of personal care products (PCPs) during showering are generated, and person-to-person variability in emissions calculated. A panel of 18 participants used a standardized set of products, dosages, and application times during showering in a controlled indoor bathroom setting. Proton transfer mass spectrometry was used to measure the in-room VOC evolution of limonene (representing the sum of monoterpenes), benzyl alcohol, and ethanol. The release of VOCs had reproducible patterns between users, but noticeable variations in absolute peak concentrations, despite identical amounts of material being used. The amounts of VOC emitted to air for one showering activity were as follows: limonene (1.77 mg ± 42%), benzyl alcohol (1.07 mg ± 41%), and ethanol (0.33 mg ± 78%). Real-world emissions to air were between 1.3 and 11 times lower than bottom-up estimates based on dynamic headspace measurements of product emissions rates, likely a result of PCPs being washed away before VOC evaporation could occur.

Background: Pain of the hand distal interphalangeal joints may result from trauma, osteoarthritis or inflammatory arthritis. When symptoms are not controlled by non-operative means, surgical arthrodesis may be performed, resulting in complete stiffness of the joint and possible weakening of grip strength. This study aims to quantify the effect of a stiff ring finger distal interphalangeal joint on overall grip strength.Methods: One hundred participants were screened to exclude upper limb pathology. A Jamar dynamometer was used to assess overall hand grip strength. A splint was used to prevent distal interphalangeal joint flexion, thus replicating a fused distal interphalangeal joint. Participants were tested with and without the splint and the results compared. The mean of three grip strength tests was taken.Results: The participants included 55 females. Mean age was 31 (18–60 years). 76 participants had a reduction in grip strength with splinting, with a significant difference seen (p < 0.05) on Wilcoxon signed rank test. The median reduction in grip strength with splinting was 1.67 kg. However only 10 participants (10%) had a grip strength loss of greater than 6.5 kg, which is the minimal clinically important difference.Conclusions: This study found a significant loss in overall hand grip strength when the ring finger distal interphalangeal joint was stiffened. However, despite this significant change, only 10 (10%) participants experienced a reduction of greater than 6.5 kg. This is the level of weakness felt to be required to reduce function. Thus our results suggest that 90% of patients with a stiff ring finger distal interphalangeal joint are unlikely to have a clinically identifiable functional reduction in grip strength as a result.

Volatile organic compound (VOC) emissions from personal care products (PCPs) contribute to poor indoor air quality. Exposure to indoor VOCs is typically determined through ambient concentration measurements; however, for some PCPs the proximity of use to the nose and mouth may lead to disproportionately large inhaled doses. In this paper, we quantify emission factors for six common PCP ingredient VOCs (ethanol, 2-propanol, benzyl alcohol, 1,3-butanediol, t-butyl alcohol, and the grouping of monoterpenes as limonene) from 16 facial day-moisturizers using headspace analysis and selected ion flow-tube mass spectrometry. A wide range of emissions rates were observed across the range of products tested (e.g., ethanol 3.3-6.9 × 102 µg s-1 g[product]-1 , limonene 1.3 × 10-1 -4.1 × 10-1 µg s-1 g[product]-1 ). We use a mannequin head with reconstructed nose and mouth airways to sample VOCs from facial application at typical respiration volumes. A single facial application of moisturizer can lead to a much larger inhaled VOC dose than would be inhaled from typical indoor ambient air over 24 h (e.g., limonene up to ~×16 greater via facial application, ethanol up to ~×300). Emissions from facially applied PCPs typically decayed to background concentrations over periods ranging from 5 to 150 min.

This prospective single-centre study describes the functional outcomes, satisfaction and health-related quality of life after open revision carpal tunnel decompression for recurrent carpal tunnel syndrome. The QuickDASH, patient satisfaction and EuroQol-5 dimensions questionnaires were collected preoperatively and postoperatively over a 5-year period (2013–2018). The median time to revision was 13.3 years (range 3.9–35.4 years; interquartile range 7.2–15.9 years). Outcomes were available for 14 hands in 13 patients at a mean of 20 months after revision surgery. The mean preoperative and postoperative QuickDASH scores were 55 and 29, respectively, and the mean improvement in QuickDASH was 26. The mean improvement in EuroQol-5 dimensions score was 0.1, and 13 of the 14 patients were satisfied. The net promoter score was 85. This study confirms that patients undergoing revision open carpal tunnel decompression for recurrent carpal tunnel syndrome experience a significant improvement in function and health-related quality of life.Level of evidence: IV

Adventitious rooting ability is considered a good indicator of juvenility in trees and has often been used to assess explants subjected to treatments to alter developmental stage. However, rooting assessments are not always practical and the callusing of needles in vitro was investigated as an alternative bioassay of physiological age. Shoots were sampled from the uppermost whorl of Sitka spruce trees aged 1, 3, 4, 6, 11, 16, 21, 35 and 39 years and from the lowest whorls of 3- and 4-year-old trees. Needles were sampled for measurement of length, width, length/width ratio, projected and total surface areas, dry weight and specific leaf area. For explants of uppermost whorl origin, there were decreases in the rooting ability of cuttings and the callusing response of needles with increasing age of tree. Associated with the loss in callusing ability was an increase in the production of a black exudate. The changes with age for rooiing, callusing and exudation could each be adequately described by the Gompertz growth function which showed their rates of change to be similar. The observed changes are closely associated with changes in needle area, weight and specific leaf area. Euclidean distances (using the mean values of selected characteristics for each age class) were computed as a measure of physiological age. The shoots and needles of basal shoots are more juvenile in character than those taken from the uppermost whorls of the same trees.

Disposable compressed gas aerosols have been a ubiquitous part of life since the mid-1950s. The signing of the Montreal Protocol in 1987 led to aerosol propellants changing from halocarbons to less damaging replacements; around 93% of current aerosol emissions by mass are volatile organic compounds (VOCs), with small contributions from compressed air (6.6%) and fluorocarbons (0.4%). The global consumption of aerosol units has increased significantly since the signing of the Montreal Protocol, increasing by an order of magnitude in some countries. In high-income countries, annual consumption increased through the 1990s and 2000s, typically reaching a plateau of approximately 10 ± 3 units person–1 year–1 dependant on product preferences. The largest contributors of both units and mass emissions are personal care products (PCPs). Consumption of aerosols in lower- and upper-middle income countries are growing rapidly, for example, Brazil, Mexico, China, Thailand, all tripling reported consumption since 2006. Based on evidence drawn from national production estimates, product specifications and formulations, and interpolation of usage between countries of similar economic status, we estimate global emissions of VOC from aerosol propellants were approximately 1.3 ± 0.23 Tg year–1 in 2018. The fraction of anthropogenic VOC emissions accounted for by aerosols has in some countries increased significantly as emissions from vehicles and fuels have declined. For example, in the UK, 6.1% of anthropogenic VOC emissions were from aerosols in 2017, more than were released from gasoline passenger cars. Should low- and middle-income economies grow consumption per capita in line with recent trends, then we project global aerosol consumption may reach approximately 4.4 ± 0.96 × 1010 units year–1 in 2050. Should existing national and international policies on aerosol product formulation remain unchanged, and VOCs remain the dominant propellant, compressed aerosols could account for a global emission of approximately 2.2 ± 0.48 Tg year–1 in 2050.

Volatile organic compounds (VOCs) emitted from personal care products (PCPs) can affect indoor air quality and outdoor air quality when ventilated. In this paper, we determine a set of simplified VOC species profiles and emission rates for a range of non‐aerosol PCPs. These have been constructed from individual vapor analysis from 36 products available in the UK, using equilibrium headspace analysis with selected‐ion flow‐tube mass spectrometry (SIFT‐MS). A simplified speciation profile is created based on the observations, comprising four alcohols, two cyclic volatile siloxanes, and monoterpenes (grouped as limonene). Estimates are made for individual unit‐of‐activity VOC emissions for dose‐usage of shampoos, shower gel, conditioner, liquid foundation, and moisturizer. We use these values as inputs to the INdoor air Detailed Chemical Model (INDCM) and compare results against real‐world case‐study experimental data. Activity‐based emissions are then scaled based on plausible usage patterns to estimate the potential scale of annual per‐person emissions for each product type (eg, 2 g limonene person−1 yr−1 from shower gels). Annual emissions from non‐aerosol PCPs for the UK are then calculated (decamethylcyclopentasiloxane 0.25 ktonne yr−1 and limonene 0.15 ktonne yr−1) and these compared with the UK National Atmospheric Emissions Inventory estimates for non‐aerosol cosmetics and toiletries.

This prospective single-centre study describes the patient-reported outcomes following open in situ decompression for cubital tunnel syndrome. The Quick version of the Disabilities of the Arm, Shoulder and Hand questionnaire and patient satisfaction scores were collected over a 3-year period. Outcomes were available for 77 patients at a mean of 17 months (11–27 months) postoperatively. The mean scores improved significantly from 39 to 30 postoperatively. The score change correlated strongly and significantly with postoperative satisfaction. Sixty-six patients (86%) were satisfied. Patients with clinical evidence of weakness at presentation had significantly lower satisfaction scores than those without. By reporting functional improvement and high levels of patient satisfaction in a large series, this study supports the use of in situ decompression for cubital tunnel syndrome. The outcomes for the patients with weakness and atrophy of ulnar nerve innervated muscles before surgery are less satisfactory. Level of evidence: III

Objectives The primary aim of this study was to assess the reproducibility of the recalled preoperative Oxford Hip Score (OHS) and Oxford Knee Score (OKS) one year following arthroplasty for a cohort of patients. The secondary aim was to assess the reliability of a patient’s recollection of their own preoperative OHS and OKS one year following surgery. Methods A total of 335 patients (mean age 72.5; 22 to 92; 53.7% female) undergoing total hip arthroplasty (n = 178) and total knee arthroplasty (n = 157) were prospectively assessed. Patients undergoing hip and knee arthroplasty completed an OHS or OKS, respectively, preoperatively and were asked to recall their preoperative condition while completing the same score one year after surgery. Results A mean difference of 0.04 points (95% confidence intervals (CI) -15.64 to 15.72, p = 0.97) between the actual and the recalled OHS was observed. The mean difference in the OKS was 1.59 points (95% CI -11.57 to 14.75, p = 0.10). There was excellent reliability for the ‘average measures’ intra-class correlation for both the OHS (r = 0.802) and the OKS (r = 0.772). However, this reliability was diminished for the individuals OHS (r = 0.670) and OKS (r = 0.629) using single measures intra-class correlation. Bland–Altman plots demonstrated wide variation in the individual patient’s ability to recall their preoperative score (95% CI ± 16 for OHS, 95% CI ± 13 for OKS). Conclusion Prospective preoperative collection of OHS and OKS remains the benchmark. Using recalled scores one year following hip and knee arthroplasty is an alternative when used to assess a cohort of patients. However, the recall of an individual patient’s preoperative score should not be relied upon due to the diminished reliability and wide CI. Cite this article: T. F. M. Yeoman, N. D. Clement, D. Macdonald, M. Moran. Recall of preoperative Oxford Hip and Knee Scores one year after arthroplasty is an alternative and reliable technique when used for a cohort of patients. Bone Joint Res 2018;7:351–356. DOI: 10.1302/2046-3758.75.BJR-2017-0259.R1.

The aim of this study was to investigate the long-term outcome of simple trapeziectomy by a single surgeon and to compare this with pre-operative function. Two hundred and five patients completed the shortened disabilities of the arm, shoulder and hand questionnaire (QuickDASH) and the EuroQoL five-dimensional questionnaire (EQ-5D) scores at a mean of 8.2 (range 3.5–17) years after simple trapeziectomy. There were no pre-operative scores available, so case controls were selected from our prospective database to compare pre- and post-operative patient-reported outcome measures. The mean QuickDASH score of the post-operative matched group was 37 (SD 17.0) and the mean EQ-5D was 0.56 (SD 0.31). The mean QuickDASH score of the pre-operative group was 54 (SD 17.0). The mean difference in QuickDASH between the pre- and post-operative groups was 17 (95% CI: 8 to 26, p = 0.0003). This study demonstrated a significant and sustained improvement in patient-reported function after simple trapeziectomy. It supports that simple trapeziectomy is a simple, safe and effective treatment for advanced trapeziometacarpal joint arthritis. Level of evidence: IV

This study describes functional outcomes, patient satisfaction, and health-related quality of life (HRQoL) following open revision carpal tunnel decompression (CTD) for recurrent carpal tunnel syndrome (CTS). Postoperative results were available for 16 hands in 15 patients (100% at mean follow-up at 19.9 months). This was a prospective study at a single-centre serving a population of 360,000. QuickDASH, patient satisfaction, and EQ-5D-5L questionnaires were collected pre and postoperatively for patients undergoing revision CTD over a five-year period (2013–2018). The incidence of revision CTD was 0.9 per 100,000 patients per year. Fifteen patients reported recurrent and 1 patient-reported persistent symptoms. Median time to revision was 12.5 years (interquartile range 6.7–15.7 years). Mean preoperative and postoperative quickDASH was 57.7 and 36.1, respectively. The overall mean improvement in QuickDASH was 28.1. The mean improvement in EQ-5D-5L was 0.17. Thirteen patients (81.8%) were satisfied. The Net Promoter Score was 87.5. This study confirms the widely-held view that patients with late-presenting CTS can expect to enjoy a similar improvement in function and HRQoL as patients undergoing primary CTD. Recurrent CTS presents following a long symptom-free period after primary CTD, and hand function regresses to a similar level of disability. These results can be used to counsel patients who are considering revision surgery.

The identification of oral precancerous and cancerous lesions at an early stage allows for early intervention and minimizes mortality and morbidity. A combination of risk reduction and early detection should further reduce the incidence and improve outcomes. A clear understanding of the aetiology and clinical presentation of these lesions is key to effective management of these patients in primary dental care. We present a timely update on these issues, with an emphasis on the importance of early detection. Clinical Relevance: The identification of lesions at precancerous stages or, at worst, early malignancy, is the key to better outcomes for our oral cancer patients.

Brachymetatarsia is an abnormal shortening of a metatarsal. It causes disruption of the normal metatarsal parabola, resulting in metatarsalgia, calluses and dislocation of the digits. Patients often express discontent with the appearance of their feet. Lengthening by distraction osteogenesis and 1-stage intercalary bone grafting procedures are the mainstays of operative treatment. We present a modified 1-stage technique, combining the use of a Chevron osteotomy of the fourth metatarsal with shortening osteotomies of the second and third metatarsals. Bone removed from the third metatarsal was used to lengthen the fourth. The Chevron segments provided mediolateral, dorsoplantar, and rotational stability. The technique was used on both feet of 1 patient. The mean increase in AOFAS score was 34.5 (right foot, 46; left foot, 23.) There were no complications. A 1-stage technique does not require an external fixator or postoperative manipulation and has a quicker healing time. Taking the bone graft from neighboring metatarsals decreases the discrepancy between metatarsal lengths. A smaller increase in the length of the fourth ray is then required, and the chance of neurovascular injury as a result of soft-tissue stretching is minimized. This technique allows restoration of the metatarsal parabola and provides good correction, immediate stability, and good integration. Levels of Evidence: Therapeutic Level IV, Case Study

Dyskeratosis congenita (DC) is a rare inherited condition, first described in 1960 as Zinsser-Engmann-Cole syndrome. The condition presents with a classic triad: nail dystrophy, reticulate skin pigmentation over the trunk and neck, and white plaques typically in the oral cavity. White plaques may also affect, although less frequently, the mucosal surfaces of the urethra and vagina. Variable somatic abnormalities may be present; these include: pulmonary, gastrointestinal, genitourinary, cerebral, and dental complications. Pancytopenia eventually develops, progressing to bone marrow failure; the most common cause of death. In the X-linked form, which affects mainly males, mutations arise in the DKC-1 gene which encodes for the protein dyskerin. This report details a variant case of DC affecting a 9-year-old boy. The disease progression did not follow the "classic triad" typically seen in the condition. Longstanding nail dystrophy and oral ulceration were the sole presenting features. The details of the challenges encountered during diagnosis and treatment are further discussed.

Purpose: Limited drug penetration in solid tumors is a potential mechanism of resistance for many anticancer drugs. Taxanes represent a class of drugs that are currently undergoing a new round of development, but with little known of their ability to penetrate and distribute relative to blood vessels within solid tumors. Experimental Design: We assessed the tissue penetration of paclitaxel and docetaxel in HCT-116 tumor xenografts and in multilayered cell culture (MCC), a three-dimensional cell culture model of the tumor extravascular compartment. In xenografts, taxanes were mapped relative to blood vessels to obtain drug profiles as a function of distance from vasculature. For MCC, cultures were exposed to stirred drug reservoirs and taxanes measured as a function of depth into tissue. Results: Both taxanes exhibited limited penetration, with little drug reaching further than 100 μm into the tissue. Of the two, paclitaxel exhibited up to 2-fold greater penetration than docetaxel. Mapping tumor cell proliferation following treatment allowed the consequences of limited drug penetration to be assessed. In tumor xenografts where reduced drug exposure to cells far from vasculature is one of several factors influencing response to treatment, up to a 75% reduction in S-phase cells was achieved in cells nearest the vessels, but only 50% reduction was observed in the tissue 150 μm away. In MCC-based data, where the influence of reduced cell proliferation with depth into tissue was circumvented, a 5-fold (paclitaxel) and 10-fold (docetaxel) increase in reservoir drug concentration was required to produce a response in cells 150 μm into the tissue equivalent to that seen in cells directly exposed to the drug. Conclusion: These results indicate that limited distribution is an important mechanism of tumor resistance to taxanes.

Little is known about the current health status of US metal and nonmetal (MNM) miners, in part because no health surveillance systems exist for this population. The National Institute for Occupational Safety and Health (NIOSH) is developing a program to characterize burden of disease among MNM miners. This report discusses current knowledge and potential data sources of MNM miner health. Recent national surveys were analyzed, and literature specific to MNM miner health status was reviewed. No robust estimates of disease prevalence were identified, and national surveys did not provide information specific to MNM miners. Because substantial gaps exist in the understanding of MNM miners' current health status, NIOSH plans to develop a health surveillance program for this population to guide intervention efforts to reduce occupational and personal risks for chronic illness.

This paper describes the engineering architecture and function of the neutron Time-of-Flight (nToF) diagnostic suite installed on the National Ignition Facility (NIF) at Lawrence Livermore National Laboratory (LLNL). These instruments provide key measures of neutron yield, ion temperature, drift velocity, neutron bang-time, and neutron downscatter ratio. Currently, there are five nToFs on three collimated lines-of-site (LOS) from 18m to 27m from Target Chamber Center, and three positioned 4.5m from TCC, within the NIF Target Chamber but outside the vacuum and confinement boundary by use of re-entrant wells on three other LOS. NIF nToFs measure the time history and equivalent energy spectrum of reaction generated neutrons from a NIF experiment. Neutrons are transduced to electrical signals, which are then carried either by coaxial or Mach-Zehnder transmission systems that feed divider assemblies and fiducially timed digitizing oscilloscopes outside the NIF Target Bay (TB) radiation shield wall. One method of transduction employs a two-stage process wherein a neutron is converted to scintillation photons in hydrogen doped plastic (20x40mm) or bibenzyl crystals (280x1050mm), which are subsequently converted to an electrical signal via a photomultiplier tube or a photo-diode. An alternative approach uses a single-stage conversion of neutrons-to-electrons by use of a thin (0.25 to 2 mm) Chemical Vapor Deposition Diamond (CVDD) disc (2 to 24mm radius) under high voltage bias. In comparison to the scintillator method, CVDDs have fast rise and decay times (

Assessments of dynamic cerebral autoregulation usually measure the cerebral blood flow velocity (CBFV) response to changes in arterial blood pressure (ABP). We studied the effect of substituting ABP by cerebral perfusion pressure (CPP), expressed as the difference between ABP and intracranial pressure (ICP), in estimates of dynamic autoregulation obtained by transfer function analysis. CBFV, ABP and ICP were recorded during periods of physiological stability in 30 patients with severe head injury. Transfer function analysis was performed using the following combinations of input-output variables: ABP-CBFV, CPP-CBFV and CBFV-ICP. Frequency and time-domain (step response) functions were averaged for recordings with mean ICP20 mmHg (group A) and mean ICPor = 20 mmHg (group B). The ABP-CBFV transfer function parameters and step response for group A were similar to previous studies in normal subjects, but group B showed deterioration of dynamic autoregulation. Radically different step responses were obtained from both groups for the CPP-CBFV transfer function and the coherence was not significantly improved. The CBFV-ICP transfer function had the highest values of coherence and indicates that changes in CBFV are the cause of spontaneous fluctuations in ICP. Furthermore, the ICP step response plateau was significantly higher for group B than for group A. An alternative calculation of the CBFV step response to changes in CPP resembled the corresponding responses for the ABP input. For spontaneous fluctuations in ABP, ICP and CBFV, it is not possible to calculate the CPP-CBFV transfer function directly due to the high positive correlation between ICP and CBFV, but an alternative estimate can be obtained by using the CBFV-ICP transfer function. The latter could also be useful as a method to assess intracranial compliance in head injury patients.

Embryogenic masses (EMSes) of pistachio (Pistacia vera L.) were proliferated in liquid Murashige and Skoog (MS) medium without growth regulators. To determine the effects of benzylaminopurine (BAP), racemic (±) abscisic acid (ABA) and sucrose treatments during maturation on the subsequent germination and plantlet regeneration, clusters of mature somatic embryos were transferred from maturation medium onto the surface of 0.7% agar-solidified Murashige and Skoog medium. Neither germination nor plantlet development medium contained BAP or ABA. Germination studies were carried out using 80 somatic embryos at every combination of four sucrose concentrations, three maturation periods and either five concentrations of BAP or four of ABA, and the numbers germinating were recorded after four durations of culture. A similar experimental plan was used to study plantlet regeneration. The number of germinated somatic embryos increased markedly with duration of the culture on germination medium, and was influenced by the concentrations of BAP or ABA in the maturation medium; the concentration of sucrose in this medium had little influence. Plantlet regeneration also increased with culture duration and was reduced at the highest levels of BAP or ABA; with ABA, the probability of plantlet regeneration was lower for longer maturation periods. ABA and BAP have similar effects on somatic embryo germination (except at the highest levels used), but BAP is superior to ABA for promoting subsequent plantlet regeneration. Linear logistic models were used to investigate the significance of the treatments, and to estimate the optimum conditions for germination and plantlet regeneration.

Transformed hairy root cultures of chilli pepper (Capsicum frutescens cv. cayenne) containing the CaMV 35S promoter linked to the parsley PAL-2 cDNA were generated. These transformants showed increased PAL activity at early and late stages of culture. The morphology, colour and growth rate of these transformants were quite different from the control hairy roots. Measurements of cell dry weight, content of fibre and lignin-like material, suggested that the altered characteristics of the PAL transformants might be linked to lignification. HPLC analyses of phenolic compounds in transgenic roots revealed the accumulation of several substances that were not found in the controls. In response to the addition of salicylic acid or phenylalanine, lignification of the control hairy roots increased. However, the content of lignin-like substances in the PAL transformants was not increased by these treatments. These results indicate that lignification of the PAL transformants had reached a level that could not be further increased.

The antigen receptor diversity of pathogenic T cells in Sjögren's syndrome (SS) may have important implications in the development of the disease; cytokines from these cells and other sources also play a role in the pathogenesis of this disease. Using a semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) technique, we have attempted to correlate the presence of restriction in the T-cell receptor (TCR) repertoire with cytokine profiles. We have analysed TCR V alpha family usage, and the expression of interleukin-1alpha (IL-1alpha), IL-1beta, IL-2, IL-4, IL-6, IL-8, IL-10, IL-13, interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha), in labial biopsies from 12 patients with SS and compared these with samples from three patients with chronic sialadenitis (CS). Only one of the SS biopsies showed evidence of V alpha restriction (three out of 18 gene families). Apart from this, expression patterns were similar in both patient groups. Four of the 12 SS samples demonstrated a 'limited heterogeneity' of the V alpha repertoire with 3-4 families predominantly expressed, in particular V alpha1 and V alpha3. Peripheral blood lymphocytes were unrestricted. The cytokine profiles of the SS and CS biopsies were generally similar. However both IFN-gamma and IL-1alpha were absent from CS, but present in SS samples. The expression of IFN-gamma in the majority of the samples, together with a lack of IL-4 and IL-13 mRNA, suggests the predominance of a Th1 response in SS. There was no clear association between the repertoire of V alpha genes expressed and the cytokine profile observed. However, the V alpha restriction in one SS sample did correspond with a limited diversity of cytokines detected.

Hypocotyl explants of chilli pepper (Capsicum frutescens) were inoculated with Agrobacterium rhizogenes strain A13 harbouring the binary vector pBI121, which contains the CaMV 35S promoter linked to the GUS reporter gene. After 4 weeks of culture, the hairy roots produced were transferred onto Schenk and Hildebrandt (SH) medium supplemented with 250mgl-1 Cefotaxime. Subsequently they were selected in liquid SH medium containing 20mgl-1 kanamycin. When treated with X-glucuronide, vascular and root tip tissues were predominantly stained. A phenylalanine ammonia-lyase (PAL) cDNA from parsley (Petroselinum) was subsequently linked to the 35S promoter and transferred into hairy roots using the same A. rhizogenes strain. Successful transformation was confirmed by Southern hybridisation. Hairy roots containing the PAL transgene showed different PAL activity, slow growth and altered morphology.

Summary Nicotine N -demethylation to nornicotine has been studied in cell-free preparations from cell suspension cultures of Nicotiana tabacum , in attempt to explore the mechanism of this enzymatic reaction. Subcellular fractionation of the homogenate using isopycnic differential centrifugation, together with TEM, showed that most of the enzyme activity (2.8 × 10 −5 U) was present in the intermediate pellet whilst the maximum specific activity of 8.8 × 10 −5 U per mg protein appeared to be associated with the microsomal fraction. The addition of selected putative methyl group acceptors, i.e. putrescine, glycine and ethanolamine, to either dialysed or undialysed enzyme preparations, did not promote enzyme activity. In addition, studies involving Sephadex G-25 gel filtration showed that molecules smaller than 5,000 MW are unlikely to be involved in this reaction. The current findings appear to support an oxidative nicotine N -demethylation and, together with the results from previous studies, provide some tentative evidence for the involvement of cytochrome P-450 in nicotine N -demethylation. The possible mechanism is also discussed.

The neutron spectrum produced by deuterium-tritium (DT) inertial confinement fusion implosions contains a wealth of information about implosion performance including the DT yield, ion-temperature, and areal-density. The Magnetic Recoil Spectrometer (MRS) has been used at both the OMEGA laser facility and the National Ignition Facility (NIF) to measure the absolute neutron spectrum from 3 to 30 MeV at OMEGA and 3 to 36 MeV at the NIF. These measurements have been used to diagnose the performance of cryogenic target implosions to unprecedented accuracy. Interpretation of MRS data requires a detailed understanding of the MRS response and background. This paper describes ab initio characterization of the system involving Monte Carlo simulations of the MRS response in addition to the commission experiments for in situ calibration of the systems on OMEGA and the NIF.

This review attempts to present an overall strategy for the production of useful secondary metabolites by cultured plant cells. After consideration of the nature and utility of secondary metabolites and the possible role of these substances to the plant, the review focuses attention on the properties of the plant cells in culture and how the cell populations and their physical and chemical environment can be manipulated to encourage the synthesis and accumulation of secondary products. Finally, consideration is given to the involvement of genetic engineering in the production of cells to perform particular metabolic tasks and how these techniques might contribute to the development of a new strategy to enable the production of useful secondary metabolites on a commercial scale. CONTENTS Summary 553 I. Introduction 553 II. Development of a strategy 555 III. Concluding remarks 565 Acknowledgements 565 References 565.

The activity of the enzyme(s) catalysing the bioconversion of nicotine to nornicotine has been demonstrated, for the first time, in cell-free preparations from tobacco cell cultures. Using 14 C-assay, it has been shown that a maximal specific activity of ca 0.2 pkat mg protein −1 is present exclusively in the supernatant fraction after centrifugation at 8 800 g . The enzyme has a pH optimum between 9.0 and 9.5, and a temperature optimum between 25 and 30°, while the V max and the apparent K m are 7.6 × 10 −2 pkat and 7.4 μM of 14 C-nicotine, respectively. The decline in enzyme activity, following the removal of some endogenous co-factors and co-enzymes by dialysis of the crude enzyme preparation, can be restored and indeed enhanced by the addition of NADPH, suggesting that this enzyme may be NADPH dependent.

Radioactive feeding experiments, in which dl -[pyrrolidine-2′- 14 C]-nicotine was added to 10-day-old cultures, confirmed that the kinetic pattern of this N -demethylation was similar to that of non-radioactive nicotine, and that nornicotine, the major product, was produced intracellularly with a maximum percentage conversion of about 70%. The appearance of nornicotine paralleled the disappearance of the added nicotine, although small amounts of radioactive metabolites other than nornicotine were also observed. One of these metabolites was tentatively identified by GC-MS as N -formyl-3′-nornicotine which is probably a side-product rather than an intermediate in nicotine N -demethylation. Nornicotine produced from added (−)-nicotine by the cultures was determined using both polarimetry and chiral GC, and shown to be exclusively one enantiomer. This provided strong evidence that the mechanism of this reaction in cultured cells was unlikely to involve opening of the pyrrolidine ring and, therefore, differed from that previously hypothesized for the tobacco plant. The possible mechanism for this reaction is also discussed.

Embryogenic tissue was produced from kernels of immature fruits of Pistachio (Pistacia vera L.) cultured in liquid Murashige and Skoog media, supplemented with 200 mgl−1 casein hydrolysate, 114 μM 1-ascorbic acid, and benzylaminopurine. Compact embryogenic masses differentiated directly from the fruit explants after culture for 2 weeks in liquid medium with 8.9 μM benzylaminopurine. After transfer of the embryogenic masses into the same medium, but with 4.4 μM benzylaminopurine, somatic embryos appeared. Several stages of embryogenesis were present in the cultures. Adventive embryos were readily separated from the friable embryogenic masses by shaking. Separated somatic embryos, germinated on solidified Murashige & Skoog medium without growth regulators, developed into plantlets.

This study examined the correlation between the worst abbreviated injury scale 1990 (AIS) intracranial severity score and outcome following severe head injury. The initial CT scans of 109 severly head injury patients were examined by a neuroradiologist and classified according to the worst applicable intracranial severity code from the AIS. This score was then correlated with the glasgow outcome scale (GOS) at 6 months. For comparison, the GOS was also correlated with the diffuse injury scale (DIS) described by L.F. Marshall et al. [5], the worst post-resuscitation Glasgow coma score (GCS) in the first 24 h, and the head injury outcome prediction tree described by Choi et al. [1]. Our results show Spearman rank correlation coefficients of 0.58 (p

A north pole NTOF system for neutron spectroscopy is being implemented at the NIF. The design is centered around a fast scintillator with low mass housing fielded 21.6m from target chamber center at θ=18°,=304°. The line-of-sight (LOS) features a primary port collimator, two secondary collimators in the intervening concrete floors, and a beam dump with a backscatter shield. Because the detector is being fielded on the roof of the NIF building, diagnostic options such as optical and electrical attenuation are remotely controlled, saving setup time and increasing shot rate. The expected performance of the diagnostic is excellent with high sensitivity to both high-energy reaction-in-flight neutrons as well as lower energy down-scattered neutrons.

A 16 year old right hand dominant schoolboy presented to the emergency department with a painful, swollen right ring finger. Three days earlier he had injured his finger playing rugby and he thought the injury occurred while he was tackling an opponent. Although he was able to finish the game he has had discomfort and reduced movement in the finger since. Ecchymosis and tenderness were noted over the distal phalanx on the palmar aspect of his hand, as well as some swelling and tenderness at the base of the ring finger (fig 1⇓). The finger had no neurovascular deficit and examination of the rest of the right hand was normal. No fracture was seen on a plain radiograph of the ring finger. Fig 1 The patient’s right hand in a relaxed posture showing loss of normal cascade of the ring finger 1. What key aspect of the clinical examination would confirm the diagnosis? 2. What is the name of this injury (the name provides a clue to its mechanism)? 3. Which finger is most commonly affected? 4. How are these injuries classified? 5. How are these injuries managed? ### 1. What key aspect of the clinical examination would confirm the diagnosis? #### Short answer Inability to actively flex the distal interphalangeal joint (DIPJ) is pathognomonic of rupture of the flexor digitorum profundus (FDP) tendon. To test the FDP tendon function, isolate the DIPJ by holding the proximal interphalangeal joint (PIPJ) in extension, thereby preventing the action of the flexor digitorum superficialis (FDS). #### Discussion FDP tendon avulsion is diagnosed on physical examination—patients have a lack of isolated DIPJ flexion. To test for this, the DIPJ is isolated by holding the PIPJ in extension (fig 2⇓). The finger will probably be painful and swollen. Ecchymosis may be present on the volar side of the finger. The affected finger is often in an extended position relative to the other fingers, with loss of …

Twenty clones established from single cells of a suspension culture of Capsicum frutescens were maintained as callus and in suspension over a sixteen week culture period. These clones exhibited marked differences in growth, chlorophyll and chloroform-soluble phenolic content which became more apparent with increasing time in culture. Clones in suspension exhibited a more rapid change in morphology and biosynthetic activity than those cultured as callus. Elicitation increased PAL activity, reduced the incorporation of L-[U-14C] phenylalanine into the chloroform-soluble fraction of the culture medium and increased incorporation into the methanol-soluble fraction of the cells in ten suspension clones. Differences to elicitation were observed among clones; in particular the faster growing isolates incorporated more radioactive label into soluble phenolics that remain in the cells than those that are released into the medium. The implications of these results are discussed.

summary Examination of cryo-sections from mature rhizomes, immature rhizomes and adventitious roots of ginger, Zingiber officinale Roscoe, showed the presence of yellow-pigmented cells. There is a correlation between the number of pigrnenteci cells and the amount of [6]-gingerol, the main pungent principle in ginger, in these organs. It is also shown histochemically and microspectrophotometrically that the yellow cells contain, in addition to flavonoid-like compounds, possibly cureumin derivatives, phenolics and large amounts of lipid material. Low-temperature scanning electron microscopy also demonstrates the oil content of these cells. Therefore, it would appear that the site of accumulation of flavonoids, curcumin derivatives, phenolics including gingerol and the essential oils of this spice lies within the same cell type.

The production of capsaicinoids in fruits of Capsicum frutescens takes place after the increase in fruit length has ceased. However, before the ons

The National Ignition Facility (NIF) successfully completed its first inertial confinement fusion (ICF) campaign in 2009. A neutron time-of-flight (nTOF) system was part of the nuclear diagnostics used in this campaign. The nTOF technique has been used for decades on ICF facilities to infer the ion temperature of hot deuterium (D(2)) and deuterium-tritium (DT) plasmas based on the temporal Doppler broadening of the primary neutron peak. Once calibrated for absolute neutron sensitivity, the nTOF detectors can be used to measure the yield with high accuracy. The NIF nTOF system is designed to measure neutron yield and ion temperature over 11 orders of magnitude (from 10(8) to 10(19)), neutron bang time in DT implosions between 10(12) and 10(16), and to infer areal density for DT yields above 10(12). During the 2009 campaign, the three most sensitive neutron time-of-flight detectors were installed and used to measure the primary neutron yield and ion temperature from 25 high-convergence implosions using D(2) fuel. The OMEGA yield calibration of these detectors was successfully transferred to the NIF.

Two rapid techniques of column chromatography, flash chromatography and vacuum chromatography, together with solvent systems differing in polarity, have been used to separate the pungent principles (gingerols and shogaols) of an extract of ginger powder. Gingerols consist of a homologous series of aldols each containing a phenolic group which together with shogaols, showing similar structure, give the pungency of ginger. Thin-layer chromatographic analysis of the fractions collected from both chromatographic techniques showed that the main gingerol homologues are separated satisfactorily from the other compounds only using vacuum chromatography. These compounds were eluted with hexane-diethyl ether (30:70) and (20:80) respectively. The results obtained with flash chromatography, on the other hand, were not satisfactory.

A comparison of morphology, trichome type and duvane accumulation of tobacco shoot cultures originating from seedlings, callus and cell suspension cultures incubated on a range of cytokinin concentrations is presented. A method for the extraction and HPLC analysis of duvatrienediols from cultures is described. Duvatrienediols (DVTs) were not detected in callus or cell suspension cultures and were only detected in seedling-derived shoot cultures. Shoot development was dependent on explant type probably as a result of pre-exposure of callus and suspension cells to high auxin concentrations. Low cytokinin levels promoted shoot development whilst high cytokinin levels increased the number of shoots regenerated but retarded their development. DVT accumulation occurred only in 'normally' developed shoots with trichomes. Growth of shoot cultures in liquid medium was inhibitory to the accumulation of DVTs. Optimum conditions for the accumulation of DVTs were shown to be incubation of seedling-derived shoot cultures on media containing 10~6 M BAP solidified with agar. The yield was 120 /xg g"1 fr. wt. which is comparable to greenhouse-grown material. Both a- and /3-DVT were detected in a ratio of 5:1. The relationship between trichomes and DVT accumulation is discussed with reference to the roles of culture origin, cytokinin, trichome type and environmental effects.

This paper investigates a new metacarpophalangeal joint design aimed at treating patients with moderate to severe forms of arthritis affecting the index, long, ring, and little fingers. Current small joint arthroplasty designs, including those for the metacarpophalangeal joint of the hand, have had limited success owing to mechanical failures and can be divided into two main families: single-piece elastomer implants and surface articulating implants. The design proposed in this study involves combining the principles of a surface weight-bearing articulating implant with those of a spanning elastomeric implant. The design consists of metacarpal and proximal phalangeal articulating housings and a central flexible spanning elastomer rod that maintains the alignment of the metacarpal and proximal phalangeal components. A preliminary finite element analysis was used to investigate the stresses in the design, the wear of the articulating bearing surfaces for different material combinations, and the stresses between the central elastomer rod and the articulating housings. This preliminary analysis shows that the design should withstand the probable loading conditions experienced within the human body and that the wear rates of the articulating surfaces and the central elastomer are acceptable.

summary Plant cell suspension cultures of Nicotiana tabacum cv. Wisconsin-38 accumulate nornicotine as the major alkaloid, unlike the parent plant where nicotine predominates. Nicotine was added to cultures of this cultivar, grown with differing degrees of dependence on photosynthesis for the provision of organic constituents, and also to cultures grown on medium that was optimised for alkaloid accumulation. Under optimal conditions nicotine was converted to nornicotine at an efficiency close to 100% over 10 d. Conversion appeared to he intracellular, with nicotine being taken up from the medium, demethylated to nornicotine and the product released. Illumination of cultures caused a slight decrease in conversion but, when cultures were partially photosynthetic, both growth and the degree of biotransformation were decreased by approximately 40%. As well as the four main tobacco alkaloids several minor alkaloids were detected in cultures after incubation with added nicotine.

The effect of light on alkaloid accumulation in a range of cell cultures of tobacco was determined. Cell suspension cultures of Nicotiana tabacum L. cv. Wisconsin-38 with differing degrees of photosynthetic activity, callus cultures of N. glauca Graham, root cultures of N. rustica L. and shoot cultures of N. tabacum were used. The alkaloid content of green illuminated cultures was greatly reduced compared with non-green cultures grown in the dark, but decreased accumulation did not correlate with increasing photosynthetic activity. The accumulation of all of the major alkaloids was affected, regardless of the species of tobacco used. Transfer of N. glauca callus from the dark into the light caused a decrease in alkaloid accumulation, while moving cultures from the light into the dark resulted in an increase in alkaloid content. In root cultures light caused a reduction in growth, which affected alkaloid synthesis. In shoot cultures there were only traces of alkaloid detectable, regardless of whether or not cultures were illuminated. Light appeared to cause a non-photosynthetic suppression of alkaloid accumulation in visibly undifferentiated cultures, and this effect was modified in visibly differentiated cultures.

The objective of the study was to test the hypothesis that dynamic cerebral pressure-autoregulation is associated with the outcome of patients with severe head injury and to derive optimal criteria for future studies on the predictive value of autoregulation indices. Repeated measurements were performed on 32 patients with severe head injury. Arterial blood pressure (ABP) was measured continuously with an intravascular catheter, intracranial pressure (ICP) was recorded with a subdural semiconductor transducer and cerebral blood flow velocity (CBFV) was measured with Doppler ultrasound in the middle cerebral artery. Transfer function analysis was performed on mean beat-to-beat values, using ABP or CBFV as input variables and CBFV or ICP as the output variables. A dynamic index of autoregulation (ARI) ranging between 0 and 9 was extracted from the CBFV step response for a change in ABP. No significant differences between survivors and non-survivors were found due to mean values of ICP, ABP, CPP, CBFV, pCO2, GCS, age or heart rate. The transfer functions between ABP-ICP and CBFV-ICP did not show any significant differences either. The median [lower, upper quartiles] ARI was significantly lower for non-survivors compared with survivors [4.8 (0.0, 5.9) v. 6.9 (5.9, 7.4), p= 0.004]. The correlation between ARI and GOS was also significant (r=0.464, p=0.011). Cohen's coefficient was optimal for a threshold of ARI= 5.86 (kappa 0.51, p=0.0036), leading to a sensitivity for death of 75%, specificity=76.5%, odds ratio =9.75 and overall precision = 75.8%. The difference in ARI values between survivors and non-survivors persisted when results were adjusted for GCS (p = 0.028). A similar analysis for the Marshall CT scale did not reach significance (p = 0.072). A logistic regression analysis confirmed that apart from the ARI, no other variables had a significant contribution to predict outcome. In this group of patients, death following severe head injury could not be explained by traditional indices of risk, but was strongly correlated to indices of dynamic cerebral pressure-autoregulation extracted by means of transfer function analysis. Future studies using a prospective design are needed to validate the predictive value of the ARI index, as estimated by transfer function analysis, in relation to death and other unfavourable outcomes.

Lichen planus is a common mucocutaneous condition in which the occurrence of oral lesions has been cited as between 0.5 and 1.9% of the adult population. It is rare in childhood. Here we report three cases of children with intra oral lesions of lichen planus. Lichen planus, although reportedly rare in childhood, should be considered in the diagnosis of hyperkeratotic or erosive lesions of the oral mucosa in children.

Objectives To assess the efficacy of a novel hydrogel polymer buccal insert containing 5 mg pilocarpine in releasing the pilocarpine in a controlled fashion over a three hour period, and to assess the effects of this on quantitative tear and saliva production and the acceptability of the insert to the patient. Design This was an open, uncontrolled pilot study for which Ethics Committee approval was obtained prior to starting. Hydrogel buccal inserts containing 5 mg pilocarpine were used three times a day for seven days. Setting The Department of Oral Medicine, Glasgow Dental Hospital & School. Subjects Eight patients with Sjogren's syndrome. Main outcome measures Changes over baseline in (1) Schirmer test, (2) whole saliva flow rate, (3) oral comfort score (VAS), (4) ocular comfort score (VAS), (5) patient acceptability. Results The buccal inserts successfully released in excess of 85% of their 5 mg pilocarpine load over three hours. There was a general improvement in oral and ocular comfort scores assessed by visual linear analogue scale, and saliva and tear production generally increased. The inserts were well tolerated by all patients except one (who wore dentures). Adverse events were few and none was serious. Conclusion This novel form of buccal pilocarpine delivery demonstrated potential for use in treating patients with Sjogren's syndrome.