The EBSD spatial resolution of a Timepix-based detector in a tilt-free geometry.

Performing EBSD with a horizontal sample and a parallel EBSD detector sensor, enables safer specimen movements for data collection of large specimen areas and improves the longitudinal spatial resolution. The collection of electron backscattering patterns (EBSPs) at normal incidence to the electron beam has been revisited via the use of a direct electron detection (DED) sensor. In this article we present a fully operational DED EBSD detection system in this geometry, referred to as the tilt-free geometry. A well-defined Σ=3[101]{121} twin boundary in a Molybdenum bicrystal was used to measure the physical spatial resolution of the EBSD detector in this tilt-free geometry. In this study, two separate methods for estimating the spatial resolution of EBSD, one based on a pattern quality metric and the other on a normalised cross correlation coefficient were used. The spatial resolution was determined at accelerating voltages of 8 kV, 10 kV, 12 kV, 15 kV and 20 kV ranging from ~22-38 nm using the pattern quality method and ~31-46 nm using the normalised cross correlation method.

Enhancing resilience and self-efficacy in the parents of children with disabilities and complex health needs.

AIM: The principal aim of this study was to develop, pilot and evaluate an intervention intended to support the development of resilience and self-efficacy in parents of children with disabilities or complex health needs. BACKGROUND: Previous research has found that families often experience physical, social and emotional stress in the context of living with and caring for their disabled child. The literature indicates that a key factor in determining how well the parents of these children cope with their situation may be how resilient and self-efficacious they are. METHODS: A total of 16 parents of children with complex needs and disabilities were engaged in a series of guided conversations delivered during six contact visits with nurse co-researchers (community children's nurses who had received an intensive three-day preparation programme). The conversations, which were supported with additional material that was designed specifically for use in the study, were based around four key themes: emotional coping, practical coping, support networks and 'you and your child'. The impact of the intervention was evaluated using both qualitative and quantitative measures. FINDINGS: When interviewed, parents reported increased self-belief and self-confidence and indicated that they felt better supported and stronger as a result of the intervention. This was consistent with the quantitative evaluation which identified significant improvements on scores for active coping and self-blame on the brief COPE inventory scale and for empathy and understanding and self-acceptance on the TOPSE scale. Scores on the self-report distress thermometer demonstrated a significant reduction in self-reported distress scores at the end of the intervention period.

The dispersion-brightness relation for fast radio bursts from a wide-field survey.

Despite considerable efforts over the past decade, only 34 fast radio bursts-intense bursts of radio emission from beyond our Galaxy-have been reported1,2. Attempts to understand the population as a whole have been hindered by the highly heterogeneous nature of the searches, which have been conducted with telescopes of different sensitivities, at a range of radio frequencies, and in environments corrupted by different levels of radio-frequency interference from human activity. Searches have been further complicated by uncertain burst positions and brightnesses-a consequence of the transient nature of the sources and the poor angular resolution of the detecting instruments. The discovery of repeating bursts from one source3, and its subsequent localization4 to a dwarf galaxy at a distance of 3.7 billion light years, confirmed that the population of fast radio bursts is located at cosmological distances. However, the nature of the emission remains elusive. Here we report a well controlled, wide-field radio survey for these bursts. We found 20, none of which repeated during follow-up observations between 185-1,097 hours after the initial detections. The sample includes both the nearest and the most energetic bursts detected so far. The survey demonstrates that there is a relationship between burst dispersion and brightness and that the high-fluence bursts are the nearby analogues of the more distant events found in higher-sensitivity, narrower-field surveys5.

Breeding biology and the evolution of dynamic sexual dichromatism in frogs.

Dynamic sexual dichromatism is a temporary colour change between the sexes and has evolved independently in a wide range of anurans, many of which are explosive breeders wherein males physically compete for access to females. Behavioural studies in a few species indicate that dynamic dichromatism functions as a visual signal in large breeding aggregations; however, the prevalence of this trait and the social and environmental factors underlying its expression are poorly understood. We compiled a database of 178 anurans with dynamic dichromatism that include representatives from 15 families and subfamilies. Dynamic dichromatism is common in two of the three subfamilies of hylid treefrogs. Phylogenetic comparative analyses of 355 hylid species (of which 95 display dynamic dichromatism) reveal high transition rates between dynamic dichromatism, ontogenetic (permanent) dichromatism and monochromatism reflecting the high evolutionary lability of this trait. Correlated evolution in hylids between dynamic dichromatism and forming large breeding aggregations indicates that the evolution of large breeding aggregations precedes the evolution of dynamic dichromatism. Multivariate phylogenetic logistic regression recovers the interaction between biogeographic distribution and forming breeding aggregations as a significant predictor of dynamic dichromatism in hylids. Accounting for macroecological differences between temperate and tropical regions, such as seasonality and the availability of breeding sites, may improve our understanding of ecological contexts in which dynamic dichromatism is likely to arise in tropical lineages and why it is retained in some temperate species and lost in others.

Comparison of veterinary drugs and veterinary homeopathy: part 1.

For many years after its invention around 1796, homeopathy was widely used in people and later in animals. Over the intervening period (1796-2016) pharmacology emerged as a science from Materia Medica (medicinal materials) to become the mainstay of veterinary therapeutics. There remains today a much smaller, but significant, use of homeopathy by veterinary surgeons. Homeopathic products are sometimes administered when conventional drug therapies have not succeeded, but are also used as alternatives to scientifically based therapies and licensed products. The principles underlying the veterinary use of drug-based and homeopathic products are polar opposites; this provides the basis for comparison between them. This two-part review compares and contrasts the two treatment forms in respect of history, constituents, methods of preparation, known or postulated mechanisms underlying responses, the legal basis for use and scientific credibility in the 21st century. Part 1 begins with a consideration of why therapeutic products actually work or appear to do so.

Comparison of veterinary drugs and veterinary homeopathy: part 2.

Part 2 of this narrative review outlines the theoretical and practical bases for assessing the efficacy and effectiveness of conventional medicines and homeopathic products. Known and postulated mechanisms of action are critically reviewed. The evidence for clinical efficacy of products in both categories, in the form of practitioner experience, meta-analysis and systematic reviews of clinical trial results, is discussed. The review also addresses problems and pitfalls in assessing data, and the ethical and negative aspects of pharmacology and homeopathy in veterinary medicine.

Sexual selection predicts brain structure in dragon lizards.

Phenotypic traits such as ornaments and armaments are generally shaped by sexual selection, which often favours larger and more elaborate males compared to females. But can sexual selection also influence the brain? Previous studies in vertebrates report contradictory results with no consistent pattern between variation in brain structure and the strength of sexual selection. We hypothesize that sexual selection will act in a consistent way on two vertebrate brain regions that directly regulate sexual behaviour: the medial preoptic nucleus (MPON) and the ventromedial hypothalamic nucleus (VMN). The MPON regulates male reproductive behaviour whereas the VMN regulates female reproductive behaviour and is also involved in male aggression. To test our hypothesis, we used high-resolution magnetic resonance imaging combined with traditional histology of brains in 14 dragon lizard species of the genus Ctenophorus that vary in the strength of precopulatory sexual selection. Males belonging to species that experience greater sexual selection had a larger MPON and a smaller VMN. Conversely, females did not show any patterns of variation in these brain regions. As the volumes of both these regions also correlated with brain volume (BV) in our models, we tested whether they show the same pattern of evolution in response to changes in BV and found that the do. Therefore, we show that the primary brain nuclei underlying reproductive behaviour in vertebrates can evolve in a mosaic fashion, differently between males and females, likely in response to sexual selection, and that these same regions are simultaneously evolving in concert in relation to overall brain size.

Survey of veterinary clients' perceptions of informed consent at a referral hospital.

This retrospective questionnaire study evaluates the perceptions of veterinary clients of the informed consent process and the consent form in a veterinary referral hospital. Replicating a validated perception survey from human medicine, 470 clients at the Queen Mother Hospital for Animals were surveyed on their perceptions during the consenting process through postal survey examining their understanding, experience and recall of informed consent. Of the 165 responses (35 per cent response rate), the majority of clients recalled the process and signing the form; however, half of the clients did not feel in control (51 per cent) or reassured (53 per cent) by the process. There was limited understanding of the purpose of consent, with 45 per cent thinking it removed their right to compensation for negligence and 31 per cent thought the veterinarian could do something different from the agreed procedure. Sixty per cent of clients did not read the form, as they trusted their veterinarian, but 33 per cent of clients felt frightened by the process. This survey highlights the need to understand the process of consent from the client's perspective, and adapt the consenting process to incorporate this into professional communication to ensure that the professional and contractual objectives of consent are met fully.

Plasma total bilirubin levels predict amputation events in type 2 diabetes mellitus: the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study.

AIMS/HYPOTHESIS: Bilirubin has antioxidant and anti-inflammatory activities. Previous studies demonstrated that higher bilirubin levels were associated with reduced prevalence of peripheral arterial disease (PAD). However, the relationship between bilirubin and lower-limb amputation, a consequence of PAD, is currently unknown. We hypothesised that, in patients with type 2 diabetes, bilirubin concentrations may inversely associate with lower-limb amputation. METHODS: The relationship between baseline plasma total bilirubin levels and amputation events was analysed in 9,795 type 2 diabetic patients from the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study. The analysis plan was pre-specified. Lower-limb amputation was adjudicated blinded to treatment allocation. Relevant clinical and biochemical data were available for analyses. Amputation was a pre-specified tertiary endpoint. RESULTS: Bilirubin concentrations were significantly inversely associated with lower-limb amputation, with a greater than threefold risk gradient across levels. Individuals with lower bilirubin concentrations had a higher risk for first amputation (HR 1.38 per 5 µmol/l decrease in bilirubin concentration, 95% CI 1.07, 1.79, p = 0.013). The same association persisted after adjustment for baseline variables, including age, height, smoking status, γ-glutamyltransferase level, HbA1c, trial treatment allocation (placebo vs fenofibrate), as well as previous PAD, non-PAD cardiovascular disease, amputation or diabetic skin ulcer, neuropathy, nephropathy and diabetic retinopathy (HR 1.38 per 5 µmol/l decrease in bilirubin concentration, 95% CI 1.05, 1.81, p = 0.019). CONCLUSIONS/INTERPRETATION: Our results identify a significant inverse relationship between bilirubin levels and total lower-limb amputation, driven by major amputation. Our data raise the hypothesis that bilirubin may protect against amputation in type 2 diabetes.

Quantifying the consequences of conifer succession in aspen stands: decline in a biodiversity-supporting community.

Quaking aspen (Populus tremuloides Michaux) stands are important for biodiversity in conifer-dominated forest landscapes. Our goal was to quantify the consequences of conifer succession on understory diversity and litter quality, as well as associated changes in aspen stand condition. We studied aspen stands on national park land in the transition zone between the northern Sierra Nevada and southern Cascade mountain ranges. We field-measured ten metrics of aspen stand condition in 29 aspen stands. Along a gradient of increasing current conifer cover, we observed decreases in herbaceous species diversity and richness and an increase in forest floor O horizon depth. We interpreted aerial photos from 1952 and 1998 to determine whether directional changes in conifer cover had occurred in the stands over the past half century, and used regression modeling to associate succession with the observed range of aspen stand condition. From the period 1952 to 1998, we found that conifer encroachment occurred in half the sampled stands, with an average increase in conifer cover of 1% a year. Aspen were persistent in the remaining stands. Stand cover dynamics and percent total canopy cover interacted to influence species richness, diversity, aspen sprouting, and litter quality. In stands with conifer encroachment, both understory species richness and diversity declined. Although aspen sprouting increased, aspen establishment declined and the relative mass of woody to fine soil litter increased.

Diabetes, pre-diabetes and insulin resistance screening in Native American children and youth.

OBJECTIVES: Early identification of pre-diabetes and insulin resistance (IR) provides an important window of opportunity for diabetes prevention. Little is known about the prevalence of pre-diabetes and IR in Native American (NA) youth. We designed a cross-sectional, community-based study of NA children to estimate the prevalence of diabetes, pre-diabetes and IR and their association with other diabetes risk factors. STUDY DESIGN: NA children (5-18 years) were screened with body mass index (BMI), blood pressure, oral glucose tolerance test (OGTT), lipids, insulin and highly sensitive C-reactive protein (hsCRP), and calculated homeostatic model assessment of IR (HOMA-IR). RESULTS: Mean age of the cohort (n=201) was 10.8 ± 3.8 years (± s.d.; 94/107 M/F). BMI percentile for age and sex (BMI%) was elevated (≥ 85 th percentile) in 58.6% of 5-11 years and 51.1% of 12-18 years, and positively correlated with HOMA-IR, blood pressure, triglycerides and hsCRP (P<0.05). The prevalence rate for pre-diabetes and diabetes were 6.5% (3.5-10.8%) and 1.0% (0.1-3.6%), respectively. Mean HOMA-IR was greater in the older than younger age group while prevalence of pre-diabetes was the same. Those with pre-diabetes and diabetes had a greater HOMA-IR, abdominal circumference and BMI% than normal youth. CONCLUSION: In the first prospective, community-based screening for pre-diabetes, IR and diabetes in United States NA youth using OGTT, while the number of diabetes cases was low, pre-diabetes was found in a significant number of youth, particularly in those with BMI ≥ 95 th%. As proportions of pre-diabetes were similar in 5-11 and 12-18 year olds, diabetes risk begins early in NA youth.

Effects of fenofibrate on renal function in patients with type 2 diabetes mellitus: the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) Study.

AIMS/HYPOTHESIS: Fenofibrate caused an acute, sustained plasma creatinine increase in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) and Action to Control Cardiovascular Risk in Diabetes (ACCORD) studies. We assessed fenofibrate's renal effects overall and in a FIELD washout sub-study. METHODS: Type 2 diabetic patients (n = 9,795) aged 50 to 75 years were randomly assigned to fenofibrate (n = 4,895) or placebo (n = 4,900) for 5 years, after 6 weeks fenofibrate run-in. Albuminuria (urinary albumin/creatinine ratio measured at baseline, year 2 and close-out) and estimated GFR, measured four to six monthly according to the Modification of Diet in Renal Disease Study, were pre-specified endpoints. Plasma creatinine was re-measured 8 weeks after treatment cessation at close-out (washout sub-study, n = 661). Analysis was by intention-to-treat. RESULTS: During fenofibrate run-in, plasma creatinine increased by 10.0 µmol/l (p < 0.001), but quickly reversed on placebo assignment. It remained higher on fenofibrate than on placebo, but the chronic rise was slower (1.62 vs 1.89 µmol/l annually, p = 0.01), with less estimated GFR loss (1.19 vs 2.03 ml min(-1) 1.73 m(-2) annually, p < 0.001). After washout, estimated GFR had fallen less from baseline on fenofibrate (1.9 ml min(-1) 1.73 m(-2), p = 0.065) than on placebo (6.9 ml min(-1) 1.73 m(-2), p < 0.001), sparing 5.0 ml min(-1) 1.73 m(-2) (95% CI 2.3-7.7, p < 0.001). Greater preservation of estimated GFR with fenofibrate was observed with baseline hypertriacylglycerolaemia (n = 169 vs 491 without) alone, or combined with low HDL-cholesterol (n = 140 vs 520 without) and reductions of ≥ 0.48 mmol/l in triacylglycerol over the active run-in period (pre-randomisation) (n = 356 vs 303 without). Fenofibrate reduced urine albumin concentrations and hence albumin/creatinine ratio by 24% vs 11% (p < 0.001; mean difference 14% [95% CI 9-18]; p < 0.001), with 14% less progression and 18% more albuminuria regression (p < 0.001) than in participants on placebo. End-stage renal event frequency was similar (n = 21 vs 26, p = 0.48). CONCLUSIONS/INTERPRETATION: Fenofibrate reduced albuminuria and slowed estimated GFR loss over 5 years, despite initially and reversibly increasing plasma creatinine. Fenofibrate may delay albuminuria and GFR impairment in type 2 diabetes patients. Confirmatory studies are merited. TRIAL REGISTRATION: ISRCTN64783481.

Estimated glomerular filtration rate and albuminuria are independent predictors of cardiovascular events and death in type 2 diabetes mellitus: the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study.

AIMS/HYPOTHESIS: We investigated effects of renal function and albuminuria on cardiovascular outcomes in 9,795 low-risk patients with diabetes in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study. METHODS: Baseline and year 2 renal status were examined in relation to clinical and biochemical characteristics. Outcomes included total cardiovascular disease (CVD), cardiac and non-cardiac death over 5 years. RESULTS: Lower estimated GFR (eGFR) vs eGFR ≥90 ml min⁻¹ 1.73 m⁻² was a risk factor for total CVD events: (HR [95% CI] 1.14 [1.01-1.29] for eGFR 60-89 ml min⁻¹ 1.73 m⁻²; 1.59 [1.28-1.98] for eGFR 30-59 ml min⁻¹ 1.73 m⁻²; p < 0.001; adjusted for other characteristics). Albuminuria increased CVD risk, with microalbuminuria and macroalbuminuria increasing total CVD (HR 1.25 [1.01-1.54] and 1.19 [0.76-1.85], respectively; p = 0.001 for trend) when eGFR ≥90 ml min⁻¹ 1.73 m⁻². CVD risk was further modified by renal status changes over the first 2 years. In multivariable analysis, 77% of the effect of eGFR and 81% of the effect of albumin:creatinine ratio were accounted for by other variables, principally low HDL-cholesterol and elevated blood pressure. CONCLUSIONS/INTERPRETATION: Reduced eGFR and albuminuria are independent risk factors for cardiovascular events and mortality rates in a low-risk population of mainly European ancestry. While their independent contributions to CVD risk appear small when other risk factors are considered, they remain excellent surrogate markers in clinical practice because they capture risk related to a number of other characteristics. Therefore, both should be considered when assessing prognosis and treatment strategies in patients with diabetes, and both should be included in risk models.

Acute effects of 5-methyltetrahydrofolate on endothelial function and asymmetric dimethylarginine in patients with chronic heart failure.

BACKGROUND AND AIMS: Folic acid enhances endothelial function in vascular disease states but its effects in chronic heart failure (CHF) are largely unknown. We studied the acute effects of i.v. methyltetrahydrofolate (5MTHF), the active metabolite of folic acid, on endothelial function and asymmetric dimethylarginine (ADMA) in CHF patients. METHODS AND RESULTS: Twenty two CHF patients and 22 controls received one of the following three-step infusions (1h per each step) in a randomized, parallel group, placebo-control study: (1) active treatment (saline, 5MTHF, and 5MTHF+the endothelial nitric oxide inhibitor N(G)-monomethyl l-arginine, LNMMA); or (2) placebo (salinex3). Endothelium-dependent vasodilatation was assessed by pulse-wave analysis (salbutamol-mediated changes in augmentation index, AIx). 5MTHF did not exert any significant effects on endothelium-dependent vasodilatation both in controls [DeltaAIx post-salbutamol baseline -7.6% (-24.8/-4.1) vs. 5MTHF -5.5% (-16.7/-3.6), medians and interquartile range, and CHF patients [-1.8% (-17.3/+1.3) vs. -2.4% (-3.8/-1.2)]. However, a significant reduction in ADMA concentrations was observed in both groups [controls baseline 0.68micromol/L (0.64/0.77) vs. 5MTHF 0.65 (0.57/0.74); CHF baseline 0.76 (0.63/0.82) vs. 5MTHF 0.69 (0.66/0.71), P=0.05 for both vs. baseline and placebo. These effects persisted during co-infusion with LNMMA. CONCLUSION: 5MTHF did not affect endothelial function but significantly reduced serum ADMA concentrations both in CHF patients and controls. This suggests a direct effect of 5MTHF on ADMA metabolism.

Simultaneous measurement of urinary metanephrines and catecholamines by liquid chromatography with tandem mass spectrometric detection.

BACKGROUND: The measurement of catecholamines and metanephrines in urine is an important diagnostic test in biochemical screening for phaeochromocytoma. Tandem mass spectrometry (MSMS) has the potential to be used in a profiling method for simultaneous assay of these analytes. METHODS: Optimal conditions were established for the MSMS detection of catecholamines (noradrenalin, adrenalin and dopamine) and metanephrines (normetanephrine and metanephrine), including commercially available isotopically labelled compounds for use as internal standards. Chromatographic separation of all five polar biogenic amines was achieved under solvent conditions that were compatible with MSMS and multiple reaction monitoring. Several types of solid-phase extraction cartridge were used to investigate clean-up conditions for urine, and acid-hydrolysates of urine, prior to LC-MSMS. RESULTS: Total catecholamines and metanephrines from acid-hydrolysed urines, or free catecholamines and free metanephrines from native urines, were complexed with diphenyl-boronate and recovered in high yield from polymer cartridges after elution with formic acid. Direct injection of eluates into the LC-MSMS system allowed quantitation of catecholamines and metanephrines with a run time of 6 min per sample. Biogenic amine concentrations for patient urines and quality assurance programme samples, and assay imprecision, were similar to values obtained with high-performance liquid chromatography methods, which used electrochemical detection. In normal urines, the ratio of free to total catecholamines was around three-fold higher than the ratio of free to total metanephrines. CONCLUSION: The assay of urinary catecholamines and metanephrines can be achieved simultaneously using one LC-MSMS method, which is rapid and reduces labour and consumable costs for routine application.

A comparative analysis of mitochondrial genomes in Coleoptera (Arthropoda: Insecta) and genome descriptions of six new beetles.

Coleoptera is the most diverse group of insects with over 360,000 described species divided into four suborders: Adephaga, Archostemata, Myxophaga, and Polyphaga. In this study, we present six new complete mitochondrial genome (mtgenome) descriptions, including a representative of each suborder, and analyze the evolution of mtgenomes from a comparative framework using all available coleopteran mtgenomes. We propose a modification of atypical cox1 start codons based on sequence alignment to better reflect the conservation observed across species as well as findings of TTG start codons in other genes. We also analyze tRNA-Ser(AGN) anticodons, usually GCU in arthropods, and report a conserved UCU anticodon as a possible synapomorphy across Polyphaga. We further analyze the secondary structure of tRNA-Ser(AGN) and present a consensus structure and an updated covariance model that allows tRNAscan-SE (via the COVE software package) to locate and fold these atypical tRNAs with much greater consistency. We also report secondary structure predictions for both rRNA genes based on conserved stems. All six species of beetle have the same gene order as the ancestral insect. We report noncoding DNA regions, including a small gap region of about 20 bp between tRNA-Ser(UCN) and nad1 that is present in all six genomes, and present results of a base composition analysis.

Using acupuncture to treat depression: a feasibility study.

OBJECTIVES: To establish the feasibility of conducting a randomised controlled trial to evaluate the efficacy of acupuncture in the treatment of mild-to-moderate depression. Control group intervention, blinding of treatment, outcome measures and the acceptability of such a trial amongst participants were key factors to be addressed. The findings from this study will be used to determine the design of a phase III randomised controlled trial. DESIGN: Nineteen participants were recruited through general practices in London, UK. Participants were randomly assigned on a 2:1 basis to either 12 sessions of verum acupuncture or 12 sessions of sham acupuncture (control). Sham acupuncture involved actual needling but at sites considered to be unrelated to depression. MAIN OUTCOME MEASURES: The Beck's Depression Inventory (BDI) and the RAND 36 Item Health Survey 1.0 (RAND) were completed at baseline and at the end of treatment or at treatment dropout. All participants also attended a brief qualitative interview at the end of the study. RESULTS: Treatment dropout was low and there were high levels of patient enthusiasm for a study of acupuncture. Referrals from General Practitioners (GPs) were lower than expected. The sham control method successfully maintained participant blinding to treatment and enabled the specific (or active) component of an acupuncture intervention to be isolated and its efficacy assessed. The outcome measures were sensitive enough to record changes in depressive symptoms and quality of life and are appropriate for use in a larger trial. CONCLUSIONS: This feasibility study has provided important information that can be used to guide the design and methodology of a full-randomised controlled trial.

Identifying patients with familial hypercholesterolaemia in primary care: an informatics-based approach in one primary care centre.

BACKGROUND: Familial hypercholesterolaemia (FH) is associated with highly raised low-density lipoprotein-cholesterol and causes early-onset cardiovascular disease. Its autosomal dominant inheritance allows family cascade screening to be performed once an index case has been identified. However, the vast majority of people with FH in the United Kingdom have not been identified, and there is no national screening programme. OBJECTIVE: To assess the utility of combined computer- and notes-based searches in identifying index cases of FH in primary care, and to uncover the degree of case overlap with secondary care. METHODS: Four computer searches were conducted in one South London practice with a registered population of 12,100 patients. Selected notes were reviewed by a general practitioner and consultant lipidologist to give a Dutch score for the probability of FH. RESULTS: 402/12,100 (3.3%) patients had a Dutch score high enough to require a notes review. Twelve cases of definite FH were found, of whom two were unknown to the practice. Eight probable cases were found, seven of whom were previously unknown. 2/12 (17%) definite cases and 4/8 (50%) probable cases were unknown to a secondary care lipid clinic. 216/402 (54%) patients scored as possible cases. After specialist review 47/216 (21.8%) patients would merit recalling for a detailed family history and xanthoma examination. CONCLUSIONS: There are both diagnosed and undiagnosed cases of FH in primary care not known to secondary care. Significant potential exists to identify new cases of FH in primary care who could act as new index cases for a family screening programme.