Kismet/CHD7/CHD8 and Amyloid Precursor Protein-like Regulate Synaptic Levels of Rab11 at the Drosophila Neuromuscular Junction.

The transmembrane protein ß-amyloid precursor protein (APP) is central to the pathophysiology of Alzheimer's disease (AD). The ß-amyloid hypothesis posits that aberrant processing of APP forms neurotoxic ß-amyloid aggregates, which lead to the cognitive impairments observed in AD. Although numerous additional factors contribute to AD, there is a need to better understand the synaptic function of APP. We have found that Drosophila APP-like (APPL) has both shared and non-shared roles at the synapse with Kismet (Kis), a chromatin helicase binding domain (CHD) protein. Kis is the homolog of CHD7 and CHD8, both of which are implicated in neurodevelopmental disorders including CHARGE Syndrome and autism spectrum disorders, respectively. Loss of function mutations in kis and animals expressing human APP and BACE in their central nervous system show reductions in the glutamate receptor subunit, GluRIIC, the GTPase Rab11, and the bone morphogenetic protein (BMP), pMad, at the Drosophila larval neuromuscular junction (NMJ). Similarly, processes like endocytosis, larval locomotion, and neurotransmission are deficient in these animals. Our pharmacological and epistasis experiments indicate that there is a functional relationship between Kis and APPL, but Kis does not regulate appl expression at the larval NMJ. Instead, Kis likely influences the synaptic localization of APPL, possibly by promoting rab11 transcription. These data identify a potential mechanistic connection between chromatin remodeling proteins and aberrant synaptic function in AD.

The CHD Protein Kismet Restricts the Synaptic Localization of Cell Adhesion Molecules at the Drosophila Neuromuscular Junction.

The appropriate expression and localization of cell surface cell adhesion molecules must be tightly regulated for optimal synaptic growth and function. How neuronal plasma membrane proteins, including cell adhesion molecules, cycle between early endosomes and the plasma membrane is poorly understood. Here we show that the Drosophila homolog of the chromatin remodeling enzymes CHD7 and CHD8, Kismet, represses the synaptic levels of several cell adhesion molecules. Neuroligins 1 and 3 and the integrins αPS2 and ßPS are increased at kismet mutant synapses but Kismet only directly regulates transcription of neuroligin 2. Kismet may therefore regulate synaptic CAMs indirectly by activating transcription of gene products that promote intracellular vesicle trafficking including endophilin B (endoB) and/or rab11. Knock down of EndoB in all tissues or neurons increases synaptic FasII while knock down of EndoB in kis mutants does not produce an additive increase in FasII. In contrast, neuronal expression of Rab11, which is deficient in kis mutants, leads to a further increase in synaptic FasII in kis mutants. These data support the hypothesis that Kis influences the synaptic localization of FasII by promoting intracellular vesicle trafficking through the early endosome.

The effects of exposure to solar radiation on human health.

This assessment by the Environmental Effects Assessment Panel (EEAP) of the Montreal Protocol under the United Nations Environment Programme (UNEP) evaluates the effects of ultraviolet (UV) radiation on human health within the context of the Montreal Protocol and its Amendments. We assess work published since our last comprehensive assessment in 2018. Over the last four years gains have been made in knowledge of the links between sun exposure and health outcomes, mechanisms, and estimates of disease burden, including economic impacts. Of particular note, there is new information about the way in which exposure to UV radiation modulates the immune system, causing both harms and benefits for health. The burden of skin cancer remains high, with many lives lost to melanoma and many more people treated for keratinocyte cancer, but it has been estimated that the Montreal Protocol will prevent 11 million cases of melanoma and 432 million cases of keratinocyte cancer that would otherwise have occurred in the United States in people born between 1890 and 2100. While the incidence of skin cancer continues to rise, rates have stabilised in younger populations in some countries. Mortality has also plateaued, partly due to the use of systemic therapies for advanced disease. However, these therapies are very expensive, contributing to the extremely high economic burden of skin cancer, and emphasising the importance and comparative cost-effectiveness of prevention. Photodermatoses, inflammatory skin conditions induced by exposure to UV radiation, can have a marked detrimental impact on the quality of life of sufferers. More information is emerging about their potential link with commonly used drugs, particularly anti-hypertensives. The eyes are also harmed by over-exposure to UV radiation. The incidence of cataract and pterygium is continuing to rise, and there is now evidence of a link between intraocular melanoma and sun exposure. It has been estimated that the Montreal Protocol will prevent 63 million cases of cataract that would otherwise have occurred in the United States in people born between 1890 and 2100. Despite the clearly established harms, exposure to UV radiation also has benefits for human health. While the best recognised benefit is production of vitamin D, beneficial effects mediated by factors other than vitamin D are emerging. For both sun exposure and vitamin D, there is increasingly convincing evidence of a positive role in diseases related to immune function, including both autoimmune diseases and infection. With its influence on the intensity of UV radiation and global warming, the Montreal Protocol has, and will have, both direct and indirect effects on human health, potentially changing the balance of the risks and benefits of spending time outdoors.

Diffuse large B cell lymphoma (DLBCL) in patients older than 65 years: analysis of 3 year Real World data of practice patterns and outcomes in England.

BACKGROUND: We wished to examine treatment and outcome patterns in older diffuse large B-cell lymphoma (DLBCL) patients, with a focus on the effect of route-to-diagnosis to outcome. METHODS: Data were extracted from Public Health England's National Cancer Registration and Analysis Service between 2013 and 2015 included route-to-diagnosis, disease characteristics and survival for 9186 patients ≥65 years. Systemic Anti-Cancer Therapy data identified front-line regimens, cycles and doses. RESULTS: Route-to-diagnosis were emergency (34%), NHS urgent cancer pathway (rapid haemato-oncologist review <2 weeks), (29%) and standard GP referral (25%). The most common regimen was R-CHOP (n = 4392). 313 patients received R-miniCHOP (7% of R-CHOP). For all patients, 3-year overall survival (OS) for 65-79 years was 57% and for ≥80 years was 32%. Three-year OS for R-CHOP-treated patients diagnosed via emergency presentation was 54% (adjusted hazard ratio (HR) 1.63, p < 0.01) and 75% (adjusted HR 0.81, p < 0.01) on the NHS urgent cancer pathway (reference HR:1.00: GP referrals). 3-year OS was 54% for both R-miniCHOP and R-CHOP in ≥80 years. CONCLUSIONS: Our comprehensive population analysis is the first to show that the NHS urgent cancer pathway is associated with a superior survival after adjusting for multiple confounders. Equivalent survival for R-CHOP and R-mini-CHOP was demonstrated in those ≥80 years.

Galactose-positive adjunct cultures prevent gas formation by Paucilactobacillus wasatchensis WDC04 in a model gas production test.

Gas production by obligatory heterofermentative lactic acid bacteria such as Paucilactobacillus wasatchensis is a sporadic problem in Cheddar cheese and results in undesired slits and cracks in the cheese. Growth of Pa. wasatchensis is not rapid, which makes investigations of gas production difficult to consistently execute. A primary objective of this study was to develop a model gas production test that could be used to investigate the effect of galactose and ribose utilization on gas production by Pa. wasatchensis and determine whether galactose-fermenting adjunct cultures could prevent gas formation. Paucilactobacillus wasatchensis WDC04 was inoculated at 101 to 106 cfu/mL into carbohydrate-restricted MRS broth containing different ribose and galactose levels and incubated for up to 21 d at 23°C. Gas production in the broth was detected using a Durham tube inverted on a 6-cm-long capillary tube; cells were enumerated at 4, 8, and 12 d; and residual galactose was also measured. Gas production was sporadic except for when 105 cfu/mL of Pa. wasatchensis WDC04 was inoculated into broth containing 0.3% ribose and 0.7% galactose. In those tubes, gas production was consistently observed after 8-d incubation, by which time galactose levels had decreased to 0.15%. Co-inoculation of Pa. wasatchensis WDC04 with as few as 103 cfu/mL of a lactose-negative galactose-positive adjunct culture (Pediococcus acidilactici 23F, Lacticaseibacillus paracasei UW4, or Lactobacillus helveticus 7995) resulted in galactose depletion by d 4 and no observable gas production by d 12. With less galactose available to the slower-growing Pa. wasatchensis WDC04, its growth was limited to 108 cfu/mL when any of the adjunct cultures was co-inoculated, compared with 109 cfu/mL when grown on its own. We concluded that galactose-fermenting adjunct cultures have potential for preventing unwanted gas production in cheese by competition for resources and especially by removing the 6-carbon galactose before it can be utilized for energy by an obligatory heterofermentative lactobacilli such as Pa. wasatchensis and produce carbon dioxide.

Process evaluation of European 'Healthy Stadia' program.

Healthy Stadia (HS) is a European public health pilot-program started in 2007 to support sports stadia in promoting the health of people who work and visit sports stadia, as well as inhabitants of the surrounding communities. The aim of this study is to describe the process evaluation of the program, from its beginning in July 2007 to December 2009, in order to assess the feasibility and sustainability of an HS network across Europe. The program involved nine associate partners involved in the coordination of activities at a local level, in the recruitment of stadia, in the development of specific program tasks and in the dissemination of the program at a national level. The activities of associate partners were evaluated through structured questionnaires administered every 6 months. The questionnaire response rate from associate partners was 77.8% for the first and third evaluations and 88.9% for the second and fourth evaluations. According to the evaluation's results, several good practices such as alcohol prevention policies and those supporting people with disabilities were implemented in stadia over the course of the program. Conversely, practices supporting mental health and green transport were generally not achieved. The implemented activities mainly involved staff and visitors. Lack of human and economic resources, especially toward the end of the program, was considered the principal challenge for program development. In conclusion, the process evaluation presented the feasibility of the HS program and the development of health promoting practices in sport stadia over time.

Lung ventilation volumetry with same-breath acquisition of hyperpolarized gas and proton MRI.

The purpose of this work was to assess the reproducibility of percentage of ventilated lung volume (PV) measured from hyperpolarized (HP) (3)He and (1)H anatomical images acquired in the same breath-hold when compared with PV measured from (3)He and (1)H images from separate breath-holds. Volumetric (3)He ventilation and (1)H anatomical images of the same resolution were acquired during the same breath-hold. To assess reproducibility, this procedure was performed twice with a short gap between acquisitions. In addition, (1)H images were also acquired in a separate breath for comparison. PV ((3)He ventilated volume divided by (1)H total lung volume) was calculated using the single-breath-hold images (PV(single)) and the separate-breath-hold images (PV(separate)). Short-term reproducibility of PV measurement was assessed for both single- and separate-breath acquisitions. Dice similarity coefficients (DSCs) were calculated to quantify spatial overlap between (3)He and (1)H segmentations for the single- and separate-breath-hold acquisitions. The efficacy of using the separate-breath method combined with image registration was also assessed. The mean magnitude difference between the two sets of PV values (±standard deviation) was 1.49 ± 1.32% for PV(single) and 4.19 ± 4.10% for PV(separate), with a significant difference (p < 0.01). The mean magnitude difference between the two PV values for the registered separate-breath technique (PV(sep-registered)) was 2.27 ± 2.23%. Bland-Altman analysis showed that PV measured with single-breath acquisitions was more repeatable than PV measured with separate-breath acquisitions, regardless of image registration. DSC values were significantly greater (p < 0.01) for single-breath acquisition than for separate-breath acquisition. Acquisition of HP gas ventilation and (1)H anatomical images in a single breath-hold provides a more reproducible means of percentage lung ventilation volume measurement than the previously used separate-breath-hold scan approach, and reduces errors.

Simple methodology for the therapeutic drug monitoring of the tyrosine kinase inhibitors dasatinib and imatinib.

A simple HPLC method has been developed to measure imatinib and N-desmethylimatinib (norimatinib) in plasma or serum at concentrations attained during therapy. Adaptation of this method to LC-MS/MS also allows dasatinib assay. A small sample volume (100 µL HPLC-UV, 50 µL LC-MS/MS) is required and analysis time is <5 min in each case. Detection was by UV (270 nm) or selective reaction monitoring (two transitions per analyte) tandem mass spectrometry. Assay calibration was linear (0.05-10 mg/L imatinib, 0.01-2.0 mg/L norimatinib and 1-200 µg/L dasatinib), with acceptable accuracy (86-114%) and precision (<14% RSD) for both methods. A comparison between whole blood and plasma confirmed that plasma is the preferred sample for imatinib and norimatinib assay. For dasatinib, although whole blood concentrations were slightly higher, plasma is still the preferred sample. Despite considerable variation in the (median, range) plasma imatinib and norimatinib concentrations in patient samples [1.66 (0.02-4.96) and 0.32 (0.01-0.99) mg/L, respectively, N = 104], plasma imatinib was >1 mg/L (suggested target for response) in all but one sample from patients achieving complete molecular response. As to dasatinib, the median (range) plasma dasatinib concentration was 13 (2-143) µg/L (N = 33). More observations are needed to properly assess the potential role of therapeutic drug monitoring in guiding treatment with dasatinib.

An automated method for the measurement of a range of tyrosine kinase inhibitors in human plasma or serum using turbulent flow liquid chromatography-tandem mass spectrometry.

Tyrosine kinase inhibitors (TKIs) are used to treat a number of cancers, including chronic myeloid leukaemia and hepatocellular carcinoma. Therapeutic drug monitoring (TDM) may be indicated to (1) monitor adherence, (2) guide dosage, and (3) minimise the risk of drug-drug interactions and dose-related toxicity. On-line, automated sample preparation provided by TurboFlow technology (ThermoFisher Scientific) in conjunction with the sensitivity and selectivity of tandem mass spectrometry (MS/MS) detection may be applied to the analysis of single drugs and metabolites. We report the use of TurboFlow LC-MS/MS for the analysis of nine TKIs and metabolites (imatinib, N-desmethylimatinib, dasatinib, nilotinib, erlotinib, gefitinib, lapatinib, sorafenib, sunitinib) in human plasma or serum for TDM purposes. An Aria Transcend TLX-II system coupled with a TSQ Vantage was used. Samples (50 µL) were vortex mixed with internal standard solution (150 µL imatinib-D(8), gefitinib-D(8), sunitinib-D(10), and nilotinib-(13)C (2) (15) N(2) in acetonitrile) and, after centrifugation 100 µL supernatant were injected directly onto a 50 × 0.5-mm Cyclone TurboFlow column. Analytes were focussed onto a 50 × 2.1-mm (3 µm) Hypersil GOLD analytical column and eluted with an acetonitrile/water gradient. Analytes were monitored in selected reaction monitoring mode (positive APCI). Total analysis time was 7 min without multiplexing. Calibration was linear (R(2) > 0.99) for all analytes. Inter- and intra-assay precision (in percent relative standard deviation, RSD) was <11 % and accuracy 89-117 % for all analytes. No matrix effects were observed. This method is suitable for high-throughput TDM in patients undergoing chronic therapy with TKIs and has been utilised in the analysis of clinical samples.

The CD63 homologs, Tsp42Ee and Tsp42Eg, restrict endocytosis and promote neurotransmission through differential regulation of synaptic vesicle pools.

The Tetraspanin (Tsp), CD63, is a transmembrane component of late endosomes and facilitates vesicular trafficking through endosomal pathways. Despite being widely expressed in the human brain and localized to late endosomes, CD63's role in regulating endo- and exocytic cycling at the synapse has not been investigated. Synaptic vesicle pools are highly dynamic and disruptions in the mobilization and replenishment of these vesicle pools have adverse neuronal effects. We find that the CD63 homologs, Tsp42Ee and Tsp42Eg, are expressed at the Drosophila neuromuscular junction to regulate synaptic vesicle pools through both shared and unique mechanisms. Tsp42Ee and Tsp42Eg negatively regulate endocytosis and positively regulate neurotransmitter release. Both tsp mutants show impaired locomotion, reduced miniature endplate junctional current frequencies, and increased endocytosis. Expression of human CD63 in Drosophila neurons leads to impaired endocytosis suggesting the role of Tsps in endocytosis is conserved. We further show that Tsps influence the synaptic cytoskeleton and membrane composition by regulating Futsch loop formation and synaptic levels of SCAR and PI(4,5)P2. Finally, Tsp42Ee and Tsp42Eg influence the synaptic localization of several vesicle-associated proteins including Synapsin, Synaptotagmin, and Cysteine String Protein. Together, our results present a novel function for Tsps in the regulation of vesicle pools and provide insight into the molecular mechanisms of Tsp-related synaptic dysfunction.

What factors influence patient compliance with supportive periodontal therapy in a general practice setting?

Background The importance of supportive periodontal therapy following active treatment has been well documented but numerous studies have shown patient compliance to be poor. The aim of this study was to ascertain which factors affect patient compliance and whether this included routinely recorded periodontal indices.Methodology This was a five-year retrospective service evaluation study set within a private general dental practice. It utilised demographic and periodontal data from patients who attended the practice for chronic periodontal treatment in 2009 and ascertained whether there were links between this data and compliance with the supportive phase of periodontal treatment.Results Three hundred and ten patients satisfied the inclusion criteria of which 32.3% were categorised as compliant, 45.5% non-compliant and 22.3% erratic attenders. Patients who were statistically significantly more compliant were males (p = 0.03) and non-smokers (p = 0.01). There was a trend for older people to be more compliant; however this was not statistically significant. Plaque and bleeding scores were lower in the compliant group but only the bleeding scores were statistically significant (p = 0.03). The pocket probing depths were used as an indicator of disease severity and showed no significant relationship with compliance.Conclusion Although some of the periodontal parameters showed a statistically significant relationship with compliance, the difference between the parameters was clinically minimal suggesting that there is no definitive physical characteristic which is an indicator of patient compliance.

Time-course of PTSD symptoms in the Australian Defence Force: a retrospective cohort study.

AIMS: Understanding the time-course of post-traumatic stress disorder (PTSD), and the underlying events, may help to identify those most at risk, and anticipate the number of individuals likely to be diagnosed after exposure to traumatic events. METHOD: Data from two health surveys were combined to create a cohort of 1119 Australian military personnel who deployed to the Middle East between 2000 and 2009. Changes in PTSD Checklist Civilian Version (PCL-C) scores and the reporting of stressful events between the two self-reported surveys were assessed. Logistic regression was used to examine the association between the number of stressful events reported and PTSD symptoms, and assess whether those who reported new stressful events between the two surveys, were also more likely to report older events. We also assessed, using linear regression, whether higher scores on the Kessler Psychological Distress Scale or the Alcohol Use Disorder Identification Test were associated with subsequent increases in the PCL-C in those who had experienced a stressful event, but who initially had few PTSD symptoms. RESULTS: Overall, the mean PCL-C scores in the two surveys were similar, and 78% of responders stayed in the same PCL-C category. Only a small percentage moved from having few symptoms of PTSD (PCL-C < 30) in Survey 1 to meeting the criteria for PTSD (PCL-C ≥ 50) at Survey 2 (1% of all responders, 16% of those with PCL-C ≥ 50 at Survey 2). Personnel who reported more stressful lifetime events were more likely to score higher on the PCL-C. Only 51% reported the same stressful event on both surveys. People who reported events occurring between the two surveys were more likely to record events from before the first survey which they had not previously mentioned (OR 1.48, 95% CI (1.17, 1.88), p < 0.001), than those who did not. In people who initially had few PTSD symptoms, a higher level of psychological distress, was significantly associated with higher PCL-C scores a few years later. CONCLUSIONS: The reporting of stressful events varied over time indicating that while the impact of some stressors endure, others may increase or decline in importance. When screening for PTSD, it is important to consider both traumatic experiences on deployment and other stressful life events, as well as other mental health problems among military personnel, even if individuals do not exhibit symptoms of PTSD on an initial assessment.

Functional Image-guided Radiotherapy Planning for Normal Lung Avoidance.

For patients with lung cancer undergoing curative intent radiotherapy, functional lung imaging can be incorporated into treatment planning to modify the dose distribution within non-target volume lung by differentiation of lung regions that are functionally defective or viable. This concept of functional image-guided lung avoidance treatment planning has been investigated with several imaging modalities, primarily single photon emission computed tomography (SPECT), but also hyperpolarised gas magnetic resonance (MR) imaging, positron emission tomography (PET) and computed tomography (CT)-based measures of lung biomechanics. Here, we review the application of each of these modalities, review practical issues of lung avoidance implementation, including image registration and the role of both ventilation and perfusion imaging, and provide guidelines for reporting of future lung avoidance planning studies.

High concordance of genomic and cytogenetic aberrations between peripheral blood and bone marrow in myelodysplastic syndrome (MDS).

Bone marrow (BM) genetic abnormalities in myelodysplastic syndrome (MDS) have provided important biological and prognostic information; however, frequent BM sampling in older patients has been associated with significant morbidity. Utilizing single-nucleotide polymorphism array (SNP-A) and targeted gene sequencing (TGS) of 24 frequently mutated genes in MDS, we assessed the concordance of genetic abnormalities in BM and peripheral blood (PB) samples concurrently from 201 MDS patients. SNP-A karyotype in BM was abnormal in 108 (54%) and normal in 93 (46%) patients, with 95% (190/201) having an identical PB karyotype. The median copy number (CN) for deletions was significantly lower in BM (CN:1.4 (1-1.9)) than in PB (CN:1.5 (1-1.95), P<0.001). Using TGS, 71% (130/183) patients had BM somatic mutations with 95% (124/130) having identical mutations in PB. The mutant allele burden was lower in PB (median 27% (1-96%)) compared with BM (median 29% (1-100%); P=0.14) with no significant difference in the number, types of mutations or World Health Organization subtype. In all patients with discordant SNP (n=11) and mutation (n=6) profiles between BM and PB, shared abnormalities were always present irrespective of treatment status. Overall, 86% of patients had a clonal aberration with 95% having identical SNP-A karyotype and mutations in PB, thus enabling frequent assessment of response to treatment and disease evolution especially in patients with fibrotic or hypocellular marrows.

Use of messenger RNA differential display to identify interleukin-11-responsive genes in human umbilical cord blood mononuclear cells: IL-11 upregulates the expression of the hMAL gene.

Human umbilical cord blood (HUCB) mononuclear cells represent a source of hematopoietic stem and progenitor cells, including cells responsive to interleukin-11 (IL-11). To investigate the molecular mechanisms associated with IL-11 action, we have used HUCB mononuclear cells as a model system to identify genes that are transcriptional targets of IL-11. Using the technique of messenger RNA differential display, we have identified 17 candidate cDNA differentially expressed in mononuclear cells incubated without and with IL-11. Fifteen of these cDNA were recovered, and 11 were sequenced. DNA sequence analysis has identified one of these cDNA as being the human MAL gene, originally identified as a marker for intermediate stages of T cell differentiation. Northern analysis using a MAL-specific probe confirms the upregulation of MAL by IL-11 in HUCB cells.

Effects of vitamin D binding protein-macrophage activating factor (DBP-MAF) infusion on bone resorption in two osteopetrotic mutations.

Osteopetrosis is a heterogeneous group of bone diseases characterized by an excess accumulation of bone and a variety of immune defects. Osteopetrosis (op) and incisors absent (ia) are two nonallelic mutations in the rat which demonstrated these skeletal defects as a result of reduced bone resorption. Osteopetrotic (op) rats have severe sclerosis as a result of reduced numbers of osteoclasts which are structurally abnormal. The sclerosis in ia rats is not as severe as in op mutants; they have elevated numbers of osteoclasts, but they are also morphologically abnormal, lacking a ruffled border. Both of these mutations have defects in the inflammation-primed activation of macrophages. They demonstrate independent defects in the cascade involved in the conversion of vitamin D binding protein (DBP) to a potent macrophage activating factor (DBP-MAF). Because this factor may also play a role in the pathogenesis of osteoclastic dysfunction, the effects of ex vivo-generated DBP-MAF were evaluated on the skeletal system of these two mutations. Newborn ia and op rats and normal littermate controls were injected with DBP-MAF or vehicle once every 4 days from birth until 2 weeks of age, at which time bone samples were collected to evaluate a number of skeletal parameters. DBP-MAF treated op rats had an increased number of osteoclasts and the majority of them exhibited normal structure. There was also reduced bone volume in the treated op animals and an associated increased cellularity of the marrow spaces. The skeletal sclerosis was also corrected in the ia rats; the bone marrow cavity size was significantly enlarged and the majority of the osteoclasts appeared normal with extensive ruffled borders.

Translocation (9;17) a novel translocation in acute myeloid leukaemia.

We report a case of AML, acute myeloid leukaemia, with a novel translocation involving the short arms of chromosomes 9 and 17. The acute myeloid leukaemia was morphologically classified as FAB subtype M2. A prolonged remission was induced with chemotherapy, followed by a relapse which was associated with the finding of the same translocation.

Pre-ALL and non-A, non-B hepatitis infection.

We report a case of acute lymphoblastic leukaemia which presented as hypoplastic anaemia following Non-A, Non-B viral hepatitis infection. The role of infection and the mechanisms involved in the evolution of pre-ALL to overt leukaemia remain speculative. However, it is of practical importance to distinguish pre-ALL from aplastic anaemia and the myelodysplastic syndromes during the early pancytopenic phase to avoid inappropriate management.

Magnetic impedance tomography.

Tissue can be characterized by its electrical impedance, especially if measurement can be extended over a range of frequencies. Recently, there has been a great deal of interest in imaging the distribution of electrical impedance through the technique of electrical impedance tomography (EIT). However, EIT has a number of practical problems relating to the placement of electrodes on the body. Such contacts are not required to collect magnetic field data around an object through which current is flowing and thus this approach may be more practical than EIT in the clinical environment. This paper describes the technique of magnetic impedance tomography (MIT), which allows reconstruction of the current distribution from magnetic field measurements. The reconstruction techniques used to generate the images and the prototype data collection system are described. Images produced using data collected from discrete and distributed current phantoms and the thorax during human respiration are presented.

Immediate knowledge increase from an oral cancer information leaflet in patients attending a primary health care facility: a randomised controlled trial.

The aim was to determine the immediate influence of a validated patient information leaflet (PIL) on oral cancer and knowledge in primary care attenders. Participants were patients (n=800) attending their primary health care provider from 14 general practices (eight dental and six medical) in the north west of England. Measures were a previously validated knowledge questionnaire (36 dichotomous items), self-reported dental service attendance history and demographic variables. The results showed that patients who had read the oral cancer PIL demonstrated a significant increase in knowledge regardless of clinical setting (F[1,739]=246.24, P<0.0001). Patients showed improvements in selecting the correct signs and risk factors associated with disease. Immediate knowledge gain from a simple PIL about oral cancer was found and independent of the primary care facility, where the PIL was distributed.