"Smoking during pregnancy - Perinatal outcomes, financial implications, and tobacco treatment services".

Objective: Smoking in pregnancy is the leading modifiable risk factor for poor pregnancy outcomes. A sample population from United Lincolnshire Hospital NHS Trust (ULHT), with the highest prevalence of smoking at the time of delivery (SATOD) in England from April 2020 to March 2021 was studied. The project mapped the journey of women who smoked during pregnancy until birth and compared with a non-smoking cohort. In addition, it explored the options for possible changes to the current tobacco treatment service and importance of catering to the population demographics. Methods: Data was analysed using Chi-squared or Mann Whitney and student T-test for categorical and continuous variables respectively. A p-value of < 0.05 was considered statistically significant. Results: All women who smoked during pregnancy were referred to the stop smoking service. However, only 34.9 % accessed the service. Smoking mothers were younger (P = 0.001), had more complex obstetric history (P = 0.044), required increased fetal surveillance (P=<0.001), delivered at an earlier gestation (P = 0.033), and had babies with lower birth-weight (P=<0.001) compared to non-smokers. In addition, women who smoked demonstrated a downward trend in breast feeding their babies at birth and on discharge (P=<0.001 and P=<0.001 respectively). Conclusions: Findings from the study informed a successful business case for improvements to the current tobacco treatment service and the development of in-house maternity model for pregnant smokers at ULHT.

Tailoring the homing capacity of human Tregs for directed migration to sites of Th1-inflammation or intestinal regions.

Cell-based therapy with CD4+ FOXP3+ regulatory T cells (Tregs) is a promising strategy to limit organ rejection and graft-vs-host disease. Ongoing clinical applications have yet to consider how human Tregs could be modified to direct their migration to specific inflammation sites and/or tissues for more targeted immunosuppression. We show here that stable, homing-receptor-tailored human Tregs can be generated from thymic Tregs isolated from pediatric thymus or adult blood. To direct migration to Th1-inflammatory sites, addition of interferon-γ and IL-12 during Treg expansion produced suppressive, epigenetically stable CXCR3+ TBET+ FOXP3+ T helper (Th)1-Tregs. CXCR3 remained expressed after injection in vivo and Th1-Tregs migrated efficiently towards CXCL10 in vitro. To induce tissue-specific migration, addition of retinoic acid (RA) during Treg expansion induced expression of the gut-homing receptors α4ß7-integrin and CCR9. FOXP3+ RA-Tregs had elevated expression of the functional markers latency-associated peptide and glycoprotein A repetitions predominant, increased suppressive capacity in vitro and migrated efficiently to healthy and inflamed intestine after injection into mice. Homing-receptor-tailored Tregs were epigenetically stable even after long-term exposure to inflammatory conditions, suppressive in vivo and characterized by Th1- or gut-homing-specific transcriptomes. Tailoring human thymic Treg homing during in vitro expansion offers a new and clinically applicable approach to improving the potency and specificity of Treg therapy.

Sonographically guided intratendinous injections of hyperosmolar dextrose/lidocaine: a pilot study for the treatment of chronic plantar fasciitis.

OBJECTIVE: To report on the effectiveness of sonographically guided injections of hyperosmolar dextrose at reducing the pain associated with chronic plantar fasciitis. DESIGN: Case series. SETTING: Ultrasound division of St Paul's Hospital. PATIENTS: 20 referrals (3 men, 17 women; age 51 (SD 13) years) from local sports medicine primary care practitioners who had failed previous conservative treatments. INTERVENTIONS: A 27-gauge needle administered a 25% dextrose/lidocaine solution under sonographic guidance at 6 week intervals returning for a median of three consultations. MAIN OUTCOME MEASURES: Visual analogue scale (VAS) items for pain levels at rest (VAS1), activities of daily living (VAS2), and during or after physical activity (VAS3) were recorded at baseline and at the final treatment consultation (post-test). A telephone interview conducted an average of 11.8 months after the post-test consultation provided a measure of long-term follow-up. RESULTS: 16 patients reported a good to excellent outcome, while the symptoms in 4 patients were unchanged. There was a significant decrease (p<0.001) in all mean VAS items from pre-test to post-test: VAS1 (36.8 (SD 25.6) to 10.3 (10.9)), VAS2 (74.7 (20.8) to 25.0 (27.7)) and VAS3 (91.6 (9.2) to 38.7 (35.1)) and there were no apparent changes after the follow-up interview. CONCLUSIONS: Sonographically guided dextrose injections showed a good clinical response in patients with chronic plantar fasciitis insofar as pain was reduced during rest and activity. Further studies including a control group are needed to validate these outcomes.

Work-related repetitive strain injury and leisure-time physical activity.

OBJECTIVE: To investigate the relationship between leisure-time physical activity and work-related repetitive strain injury (RSI), adjusted for sociodemographic characteristics and work-related physical and stress factors. METHODS: The data source was the 2003 Canadian Community Health Survey, a national cross-sectional survey of 134,072 respondents. The analysis was limited to a sample of the survey population reporting full-time work during the past 12 months (n = 58,622). The outcome of interest was work-related RSI of the upper body. Multiple logistic regression was used to examine the relationship between the outcome and leisure-time physical activity level, adjusted for sociodemographic, health, and occupational characteristics. The potential effect of leisure-time physical activity with a high upper-body load was investigated in a secondary analysis. RESULTS: The prevalence of upper-body work-related RSI was 5.9% in the Canadian population in 2003. An active lifestyle during leisure time was associated with a lower prevalence of work-related upper-body RSI (odds ratio 0.84, 99% confidence interval 0.75-0.95), after adjustment for work physical demands and other covariates. Female sex, obesity, smoking, age, work-related stress, and work physical demands were associated with RSI. In the secondary analysis, we did not find that participating in leisure-time activities with a high upper-body load was a risk factor for RSI. CONCLUSION: Our study results indicate that being physically active during leisure time is associated with a decreased risk of upper-body occupational RSI, adding another potential health benefit to participation in leisure-time physical activity.

Analysis of metal radioisotope impurities generated in [(18)O]H(2)O during the cyclotron production of fluorine-18.

We show the separation of metal radioisotope impurities using capillary electrophoresis (CE). The methodology used is an improvement of existent protocols for separation of stable metal ions. Production of fluorine-18 using [(18)O]H(2)O-enriched water encased in a titanium target body results in the production of several metal radioisotope impurities. Optimisation of the conditions for CE separation of the metal radioisotope impurities incorporated the use of 6 mM 18-Crown-6 in combination with 12 mM glycolic acid as complexing agents within the running buffer (10 mM pyridine, pH 4.0). Using this optimised procedure, we were able to separate and detect a number of metal radioisotopes, including chromium, cobalt, manganese, vanadium and berillium, within the fM concentration range.

Microfluidic reactor for the radiosynthesis of PET radiotracers.

Here we show the first application of a microfabricated reaction system to PET radiochemistry, we term "microfluidic PET". The short half-life of the positron emitting isotopes and the trace chemical quantities used in radiolabelling make PET radiochemistry amenable to miniaturisation. Microfluidic technologies are capable of controlling and transferring tiny quantities of liquids which allow chemical and biochemical assays to be integrated and carried out on a small scale. Such technologies provide distinct advantages over current methods of PET radiochemical synthesis. To demonstrate "proof of principle" we have investigated the radiohalogenation of small and large molecular weight molecules using the microfluidic device. These reactions involved the direct radioiodination of the apoptosis marker Annexin V using iodine-124, the indirect radioiodination of the anti-cancer drug doxorubicin from a tin-butyl precursor and the radiosynthesis of 2-[(18)F]FDG from a mannose triflate precursor and fluorine-18 and hence provide a test bed for microfluidic reactions. We demonstrate the rapid radioiodination of the protein Annexin V (40% radiochemical yield within 1 min) and the rapid radiofluorination of 2-[(18)F]FDG (60% radiochemical yield within 4s) using a polymer microreactor chip. Chromatographic analysis showed that the labelling efficiency of the unoptimised microfluidic chip is comparable to conventional PET radiolabelling reactions.

Microfluidic technology for PET radiochemistry.

This paper describes the first application of a microfabricated reaction system to positron emission tomography (PET) radiochemistry. We have applied microfluidic technology to synthesise PET radiopharmaceuticals using (18)F and (124)I as labels for fluorodeoxyglucose (FDG) and Annexin-V, respectively. These reactions involved established methods of nucleophilic substitution on a mannose triflate precursor and direct iodination of the protein using iodogen as an oxidant. This has demonstrated a proof of principle of using microfluidic technology to radiochemical reactions involving low and high molecular weight compounds. Using microfluidic reactions, [(18)F]FDG was synthesised with a 50% incorporation of the available F-18 radioactivity in a very short time of 4s. The radiolabelling efficiency of (124)I Annexin-V was 40% after 1 min reaction time. Chromatographic analysis showed that such reaction yields are comparable to conventional methods, but in a much shorter time. The yields can be further improved with more optimisation of the microfluidic device itself and its fluid mixing profiles. This demonstrates the potential for this technology to have an impact on rapid and simpler radiopharmaceutical synthesis using short and medium half-life radionuclides.

Nutrition support improves patient outcomes, treatment tolerance and admission characteristics in oesophageal cancer.

AIMS: Patients with oesophageal cancer undergoing chemoradiation with curative intent are at high risk of malnutrition and its complications, including increased side effects of treatment. We have developed a nutrition pathway (NP), involving the early then periodic nutrition assessment of all patients presenting to the multidisciplinary oesophageal clinic who were planned to receive definitive chemoradiation. MATERIALS AND METHODS: Patients were assessed as at 'low', 'moderate' or 'severe' nutrition risk, and were provided with appropriate nutrition intervention ranging from preventative advice (low risk), oral nutrition support (moderate risk) to enteral feeding (severe risk). Outcomes for 24 patients treated before implementation of the NP were compared with those of 24 patients treated using the NP. RESULTS: Patients managed using the NP experienced less weight loss (mean weight change -4.2 kg +/-6.4 cf. -8.9 kg +/- 5.9, P = 0.03), greater radiotherapy completion rates (92% cf. 50%, P = 0.001), fewer patients had an unplanned hospital admission (46% cf. 75%, P = 0.04), and those that did had a shorter length of stay (3.2 days +/- 5.4 cf. 13.5 days +/- 14.1, P = 0.002). CONCLUSION: Early and regular nutrition assessment/intervention and a multidisciplinary approach to nutrition care results in improved treatment tolerance for patients with oesophageal cancer receiving chemoradiation.

Reframing the HIV/AIDS debate in developing countries IV: does ethics have anything to offer?

Dealing with HIV/AIDS is one of the major ethical challenges facing the world today. It is suggested that an expanded discourse on ethics, divided into three levels, can help give a fuller understanding of all aspects of the HIV/AIDS pandemic. The levels are: (1) micro level (doctor-patient relationship); (2) meso level (civic and public health ethics); and (3) macro level (ethics of international relationships). At the micro level, the four principles of respect for autonomy, beneficence, non-maleficence and justice apply to HIV patients, as to any other. However, the overwhelming demand for medical care, and the lack of doctor availability in developing countries seriously limits their application. At the meso level, the Tavistock principles give a framework for health systems. The principles are: rights to health and health care; balancing resources among competing needs; comprehensiveness; cooperation among patients, clinicians and managers; focus on improvement, safety and openness. In this context, rights are respected by not discriminating on the basis of sex, geography, tribe or race. A balance has to be struck between treatment and prevention. Comprehensiveness means not ignoring palliative care and health improvement strategies. Cooperation requires 'the reciprocity and interdependence that characterise community'. The remaining principles are self-explanatory, but frequently ignored in health planning. At a macro level, there is a need for ethical discourse about issues like increasing inequality between rich and poor countries; the use of economic levers by developed countries to the disadvantage of developing countries; the international debt crisis; the tiny health care spend (US5-10 dollars per capita per annum) in Africa; and other problems like refugee and migrant labour movements. These factors fuel global instability and the HIV/AIDS pandemic, as well as contributing to the threat of terrorism and environmental degradation. We need to look at how the values of Western democracy can be revised to address these problems. For example, scientific knowledge should be made available to all who can benefit from it; individualism should be put into the context of the common good; and free market forces need to be modified to reflect the fact that we live in a world that is increasingly interdependent.

Rapid screening of 2-[18F]-fluoro-2-deoxy-D-glucose infusions for volatile organic compound contaminants by solid phase microextraction with gas chromatography-selective ion monitoring mass spectrometry (SPME-GC-SIMMS).

A method compatible with radioactive samples, capable of detecting trace volatile components in a sample volume of ca. 1cm(3) of 2-[18F]-fluoro-2-deoxy-D-glucose solution is described. The approach, based on solid phase micro-extraction gas chromatography-mass spectrometry with a carboxen/polydimethylsiloxane based fibre, was optimised with respect to extraction time (10 min), extraction temperature (60 degrees C) and phase volume ratio (1). The analysis time, including extraction, was less than 20 min with linear responses for acetonitrile and ethanol over the ranges: 0.09-80 microg cm(-3) (22 degrees C, acetonitrile) and 0.78-79 microg cm(-3) (22 degrees C, ethanol). The detection limits were estimated to be ca. 0.78 microg cm(-3) for ethanol and 0.09 microg cm(-3) for acetonitrile. Stability studies indicated analyte losses of up to 75% over 24h and analysis of aged 2-[18F]FDG samples showed that levels of ethanol and acetonitrile were not less than 100 microg cm(-3), indicative of levels substantially greater than this in the original infusions given to human subjects.

Evaluation of [4-O-methyl-(11)C]KW-6002 as a potential PET ligand for mapping central adenosine A(2A) receptors in rats.

KW-6002, a xanthine-based adenosine A(2A) antagonist, was labelled with the positron emitter carbon-11 by O-methylation of its precursor, KF23325, using [(11)C]iodomethane and was evaluated in rats as a putative in vivo radioligand for positron emission tomography (PET). Following intravenous injection of [(11)C]KW-6002, radioactivity was measured in blood, plasma, peripheral tissues, and in discrete brain tissues over a 2-h time period commensurate with PET scanning. In brain, [(11)C]KW-6002 showed highest retention in striata, with evidence of saturable binding, and lowest retention in frontal cortex (a tissue low in adenosine A(2A) receptors). PET scanning with [(11)C]KW-6002 demonstrated a specific signal in the striata which could be described using compartmental modelling. Specific binding was, however, also detected in extrastriatal regions, including brain areas reported to have low adenosine A(2A) receptor density. Blocking studies with the A(1) selective antagonist KF15372 and the non xanthine-type A(2A) antagonist ZM 241385 failed to elucidate the nature of this binding. Thus, although [(11)C]KW-6002 shows some potential for development as a PET ligand for quantifying striatal adenosine A(2A) receptor function, its in vivo selectivity requires further investigation.

Dealing with emergencies in rural areas of Europe: proceedings from WONCA Europe 2000.

On 4 July 2000, two workshops on handling emergencies in rural areas of Europe were held at the WONCA (World Organisation of National Colleges and Academies of Family Medicine/General Practice) conference in Vienna under the auspices of EURIPA (European Rural and Isolated Practitioners' Association). Papers submitted covered varying patterns of service provision and examples of short intensive training for emergencies at resident and general practitioner levels. Ways of collecting data routinely for accident prevention were also discussed. The workshops concluded that there was a need for more research in the application of emergency skills, that lack of confidence in dealing with emergencies may contribute to recruitment problems, and that further work towards a document detailing training requirements for emergencies was needed. This will be developed at a EURIPA workshop at WONCA in Tampere, June 2001.

Time-resolved characterization of diesel particulate emissions. 2. Instruments for elemental and organic carbon measurements.

The measurement of elemental carbon (EC) and organic carbon (OC) mass for particles emitted by diesel vehicles is currently accomplished using particle collection on filters, followed by analysis using the thermal/optical reflectance carbon analysis method (TOR) or one of its variations. Such filter methods limit time resolution to a minimum of several minutes, making it impossible to study emissions during transient operating conditions. Testing of five different measurement methods has demonstrated that fast response measurement of diesel exhaust particulate EC and OC concentrations, consistent with TOR filter measurements, is feasible using existing technology. EC mass concentrations are best measured through determination of particulate light absorption with a photoacoustic instrument or determination of light extinction with a smoke meter. The photoacoustic instrument has the better dynamic range and sensitivity, whereas the smoke meter is a simpler instrument. Fast response OC measurements cannot be made with any single instrument tested. However, a combination of real time weighing as implemented in the tapered element oscillating microbalance with the photoacoustic instrument has been shown to be capable of determining OC concentrations with good time response. The addition of a nephelometer to the OC measurement could potentially improve time resolution, freedom from interferences, and sensitivity.

The Rotational Spectra, Structure, Internal Dynamics, and Electric Dipole Moment of the Argon-Ketene van der Waals Complex.

Pulsed-beam Fourier transform microwave spectroscopy was used to observe and assign the rotational spectra of the argon-ketene van der Waals complex. Tunneling of the hydrogen or deuterium atoms splits the a- and b-type rotational transitions of H(2)CCO-Ar, H(2)(13)CCO-Ar, H(2)C(13)CO-Ar, and D(2)CCO-Ar into two states. This internal motion appears to be quenched for HDCCO-Ar where only one state is observed. The spectra of all isotopomers were satisfactorily fit to a Watson asymmetric top Hamiltonian which gave A=10 447.9248(10) MHz, B=1918.0138(16) MHz, C=1606.7642(15) MHz, Delta(J)=16.0856(70) kHz, Delta(JK)=274.779(64) kHz, Delta(K)=-152.24(23) kHz, delta(J)=2.5313(18) kHz, delta(K)=209.85(82) kHz, and h(K)=1.562(64) kHz for the A(1) state of H(2)CCO-Ar. Electric dipole moment measurements determined &mgr;(a)=0.417(10)x10(-30) C m [0.125(3) D] and &mgr;(b)=4.566(7)x10(-30) C m [1.369(2) D] along the a and b principal axes of the A(1) state of the normal isotopomer. A least squares fit of principal moments of inertia, I(a) and I(c), of H(2)CCO-Ar, H(2)(13)CCO-Ar, and H(2)C(13)CO-Ar for the A(1) states give the argon-ketene center of mass separation, R(cm)=3.5868(3) Å, and the angle between the line connecting argon with the center of mass of ketene and the C=C=O axis, θ(cm)=96.4 degrees (2). The spectral data are consistent with a planar geometry with the argon atom tilted toward the carbonyl carbon of ketene by 6.4 degrees from a T-shaped configuration. Copyright 2001 Academic Press.

Time resolved characterization of diesel particulate emissions. 1. Instruments for particle mass measurements.

The measurement of diesel vehicle exhaust particulate mass is currently accomplished using filter collection methods according to the Code of Federal Regulations (CFR). Such filter methods limit time resolution to a minimum of several minutes, making it impossible to study emissions during transient operating conditions. Extensive testing of five different measurement methods has demonstrated that fast response measurements of diesel exhaust particulate mass concentrations, consistent with CFR filter measurements, are feasible using existing technology. The measurement principles of choice are the real time weighing of exhaust samples as implemented in the tapered element oscillating microbalance (TEOM) and the measurement of light scattering from exhaust particles as implemented in the DustTrak nephelometer. Each of these two instruments has distinctive strengths. The TEOM excels in the area of constant calibration, independent of vehicle. For the DustTrak, this calibration varies by vehicle. On the other hand, the DustTrak has an excellent signal-to-noise ratio, freedom from interference due to other exhaust sample properties, good time resolution, and simplicity. The strengths of the two measurement methods are complimentary, so an obvious suggestion is to integrate them. The nephelometer would obtain a fast response signal, with near real time calibration provided by the microbalance.

On-road particulate matter (PM2.5 and PM10) emissions in the Sepulveda Tunnel, Los Angeles, California.

Total and speciated particulate matter (PM2.5 and PM10) emission factors from in-use vehicles were measured for a mixed light- (97.4% LD) and heavy-duty fleet (2.6% HD) in the Sepulveda Tunnel, Los Angeles, CA. Seventeen 1-h test runs were performed between July 23, 1996, and July 27, 1996. Emission factors were calculated from mass concentration measurements taken at the tunnel entrance and exit, the volume of airflow through the tunnel, and the number of vehicles passing through the 582 m long tunnel. For the mixed LD and HD fleet, PM2.5 emission factors in the Sepulveda Tunnel ranged from 0.016 (+/-0.007) to 0.115 (+/-0.019) g/vehicle-km traveled with an average of 0.052 (+/-0.027) g/vehicle.km. PM10 emission factors ranged from 0.030 (+/-0.009) to 0.131 (+/-0.024) g/vehicle. km with an average of 0.069 (+/-0.030) g/vehicle.km. The PM2.5 emission factor was approximately 74% of the PM10 factor. Speciated emission rates and chemical profiles for use in receptor modeling were also developed. PM2.5 was dominated by organic carbon (OC) (31.0 +/- 19.5%) and elemental carbon (EC) (48.5 +/- 20.5%) that together account for 79% (+/-24%) of the total emissions. Crustal elements (Fe, Mg, Al, Si, Ca, and Mn) contribute approximately 7.8%, and the ions Cl-, NO3-, NH3+, SO4(2-), and K+ together constitute another 9.8%. In the PM10 size fraction the particulate emissions were also dominated by OC (31 +/- 12%) and EC (35 +/- 13%). The third most prominent species was Fe (18.5 +/- 9.0%), which is greater than would be expected from purely geological sources. Other geological components (Mg, Al, Si, K, Ca, and Mn) accounted for an additional 12.6%. PM10 emission factors showed some dependence on vehicle speed, whereas PM2.5 did not. For test runs in which the average vehicle speed was 42.6 km/h a 1.7 times increase in PM10 emission factor was observed compared to those runs with an average vehicle speed of 72.6 km/h. Speciated emissions were similar. However, there is significantly greater mass attributable to geological material in the PM10, indicative of an increased contribution from resuspended road dust. The PM2.5 shows relatively good correlation with NOx emissions, which indicates that even at the low percent of HD vehicles, which emit significantly more NOx than LD vehicles, they may also have a significant impact on the PM2.5 levels.

Comparison and evaluation of chemically speciated mobile source PM2.5 particulate matter profiles.

Mobile sources are significant contributors to ambient PM2.5, accounting for 50% or more of the total observed levels in some locations. One of the important methods for resolving the mobile source contribution is through chemical mass balance (CMB) receptor modeling. CMB requires chemically speciated source profiles with known uncertainty to ensure accurate source contribution estimates. Mobile source PM profiles are available from various sources and are generally in the form of weight fraction by chemical species. The weight fraction format is commonly used, since it is required for input into the CMB receptor model. This paper examines the similarities and differences in mobile source PM2.5 profiles that contain data for elements, ions, elemental carbon (EC) and organic carbon (OC), and in some cases speciated organics (e.g., polycyclic aromatic hydrocarbons [PAHs]), drawn from four different sources. Notable characteristics of the mass fraction data include variability (relative contributions of elements and ions) among supposedly similar sources and a wide range of average EC:OC ratios (0.60 +/- 0.53 to 1.42 +/- 2.99) for light-duty gasoline vehicles (LDGVs), indicating significant EC emissions from LDGVs in some cases. For diesel vehicles, average EC:OC ratios range from 1.09 +/- 2.66 to 3.54 +/- 3.07. That different populations of the same class of emitters can show considerable variability suggests caution should be exercised when selecting and using profiles in source apportionment studies.

Occupational asthma cases notified to OSH from 1996 to 1999.

AIMS: To update notifications to the Occupational Safety and Health Service of the Department of Labour (OSH) Notifiable Occupational Disease System (NODS) from June 1996 to the beginning of 1999. METHODS: All notifications received for non-asbestos related occupational respiratory disease were reviewed to confirm the clinical diagnosis, occupational causation, and to identify the causative agent where possible. RESULTS: 54 cases of asthma were notified, of which 21 (39%) were accepted as being occupationally caused. These cases arose from 'predictable' industries. CONCLUSIONS: NODS offers sentinel data from interested practitioners and workplaces. Occupational asthma and other occupational respiratory diseases remain poorly notified to this system. NODS confirms the presence of occupational asthma in New Zealand from predictable and preventable causes not dissimilar to other countries. This data collection system needs supplementation by other mechanisms.