Dual-hormone artificial pancreas: benefits and limitations compared with single-hormone systems.

Technological advances have made the artificial pancreas a reality. This has the potential to improve the lives of individuals with Type 1 diabetes by reducing the risk of hypoglycaemia, achieving better overall glucose control, and enhancing quality of life. Both single-hormone (insulin-only) and dual-hormone (insulin and glucagon) systems have been developed; however, a focused review of the relative benefits of each artificial pancreas system is needed. We reviewed studies that directly compared single- and dual-hormone systems to evaluate the efficacy of each system for preventing hypoglycaemia and maintaining glycaemic control, as well as their utility in specific situations including during exercise, overnight and during the prandial period. We observed additional benefits with the dual-hormone artificial pancreas for reducing the risk of hypoglycaemic events overall and during exercise over the study duration. The single-hormone artificial pancreas was sufficient for maintenance of euglycaemia in the overnight period and for preventing late-onset post-exercise hypoglycaemia. Future comparative studies of longer duration are required to determine whether one system is superior for improving mean glucose control, eliminating severe hypoglycaemia, or improving quality of life.

Excess psychosocial burden in women with diabetes and premature acute coronary syndrome.

AIM: Diabetes is a stronger risk factor for acute coronary syndrome for women than men. We investigate whether behavioural and psychosocial factors contribute to the disparity in acute coronary syndrome risk and outcomes among women with diabetes relative to women without diabetes and men. METHODS: Among 939 participants in the GENESIS-PRAXY cohort study of premature acute coronary syndrome (age ≤ 55 years), we compared the prevalence of traditional and non-traditional factors by sex and Type 2 diabetes status. In a case-only analysis, we used generalized logit models to investigate the influence of traditional and non-traditional factors on the interaction of sex and diabetes. RESULTS: In 287 women (14.3% with diabetes) and 652 men (10.4% with diabetes), women and men with diabetes showed a heavier burden of traditional cardiac risk factors compared with individuals without diabetes. Women with diabetes were more likely to be the primary earner and have more anxiety relative to women without diabetes, and reported worse perceived health compared with women without diabetes and men with diabetes. The interaction term for sex and diabetes (odds ratio (OR) 1.40, 95% confidence intervals (95% CI) 0.83-2.36) was diminished after additional adjustment for non-traditional factors (OR 1.12, 95% CI 0.54-2.32), but not traditional factors alone (OR 1.41, 95% CI 0.84-2.36). CONCLUSIONS: We observed trends toward a more adverse psychosocial profile among women with diabetes and incident acute coronary syndrome compared with women without diabetes and men with diabetes, which may explain the increased risk of acute coronary syndrome in women with diabetes and may also contribute to worse outcomes.

Electrostatic dust collectors compared to inhalable samplers for measuring endotoxin concentrations in farm homes.

Paired electrostatic dust collectors (EDCs) and daily, inhalable button samplers (BS) were used concurrently to sample endotoxin in 10 farm homes during 7-day periods in summer and winter. Winter sampling included an optical particle counter (OPC) to measure PM2.5 and PM2.5-10 . Electrostatic dust collectors and BS filters were analyzed for endotoxin using the kinetic chromogenic Limulus amebocyte lysate assay. Optical particle counter particulate matter (PM) data were divided into two PM categories. In summer, geometric mean (geometric standard deviation) endotoxin concentrations were 0.82 EU/m(3) (2.7) measured with the BS and 737 EU/m(2) (1.9) measured with the EDC. Winter values were 0.52 EU/m(3) (3.1) for BS and 538 EU/m(2) (3.0) for EDCs. Seven-day endotoxin values of EDCs were highly correlated with the 7-day BS sampling averages (r = 0.70; P < 0.001). Analysis of variance indicated a 2.4-fold increase in EDC endotoxin concentrations for each unit increase of the ratio of PM2.5 to PM2.5-10 . There was also a significant correlation between BS and EDCs endotoxin concentrations for winter (r = 0.67; P < 0.05) and summer (r = 0.75; P < 0.05). Thus, EDCs sample comparable endotoxin concentrations to BS, making EDCs a feasible, easy to use alternative to BS for endotoxin sampling.

Augmented environments for minimally invasive therapy: implementation barriers from technology to practice.

Augmented environments for medical applications have been explored and developed in an effort to enhance the clinician's view of anatomy and facilitate the performance of minimally invasive procedures. These environments must faithfully represent the real surgical field and require seamless integration of pre- and intra-operative imaging, surgical instrument tracking and display technology into a common framework centered around the patient. However, few image guidance environments have been successfully translated into clinical use. Several challenges that contribute to the slow progress of integrating such environments into clinical practice are discussed here in terms of both technical and clinical limitations.

Salmonella enterica serovar Agona European outbreak associated with a food company.

We investigated an international outbreak of Salmonella Agona with a distinct PFGE pattern associated with an Irish Food company (company X) producing pre-cooked meat products sold in various food outlet chains in Europe. The outbreak was first detected in Ireland. We undertook national and international case-finding, food traceback and microbiological investigation of human, food and environmental samples. We undertook a matched case-control study on Irish cases. In total, 163 cases in seven European countries were laboratory-confirmed. Consumption of food from food outlet chains supplied by company X was significantly associated with being a confirmed case (mOR 18·3, 95% CI 2·2-149·2) in the case-control study. The outbreak strain was isolated from the company's pre-cooked meat products and production premises. Sufficient evidence was gathered to infer the vehicles of infection and sources of the outbreak and to justify the control measures taken, which were plant closure and food recall.

Standardisation of multilocus variable-number tandem-repeat analysis (MLVA) for subtyping of Salmonella enterica serovar Enteritidis.

Salmonella enterica serovar (S.) Enteritidis is an important cause of food-borne infection in Europe and the United States. Further subtyping of isolates is necessary to support epidemiological data for the detection of outbreaks and identification of the vehicle of infection. Multilocus variable-number tandem-repeat analysis (MLVA) is reportedly more discriminatory and produces data that are easier to share via databases than other molecular subtyping methods. However, lack of standardisation of the methodology and interpretive criteria for data analysis has meant that comparison of data between laboratories can be problematic. On the basis of MLVA profiles of 298 S. Enteritidis isolates received at the Health Protection Agency's Salmonella Reference Unit and sequence analysis of selected isolates, we propose a MLVA scheme for S. Enteritidis based on five loci (SENTR4, SENTR5, SENTR6, SENTR7 and SE-3) that have been selected from previously published S. Enteritidis MLVA schemes. A panel of reference strains has been developed that can be used by laboratories to normalise their raw fragment data to actual fragment sizes. We also provide recommendations for analysing and interpreting MLVA data. We urge laboratories to consider implementing these guidelines, thereby allowing direct comparison of data between laboratories irrespective of the platform used for fragment analysis, to facilitate international surveillance and investigation of international outbreaks.

Comparison of Droplet Size, Coverage, and Drift Potential from UAV Application Methods and Ground Application Methods on Row Crops.

Worldwide, the use of uncrewed aerial vehicles (UAVs) for pesticide application has grown tremendously in the past decade. Their adoption has been slower for Midwestern row crops. This study compared droplet size, coverage, and drift potential of sprays from UAV application methods to those from ground (implement) sprayer methods on corn in the Midwest. Droplet sizes measured during UAV spray trials [geometric mean diameters of 179 and 112 µm for UAV (boom) and UAV (no boom), respectively] were substantially smaller than those deposited during implement spray trials [mean diameters of 303 and 423 µm for implement (regular) and implement (pulse)]. Droplet coverage was high and localized in the middle swath of the field for the UAV with boom (10 to 30 droplets cm-2) and with no boom (60 droplets cm-2). Droplet coverage was broader, covering the entire field width for the implement methods (10 to 40 droplets cm-2). Vertical coverage of droplets was more uniform for UAV methods than implement methods. Although the UAVs produced smaller droplets than the implement methods, we still observed greater potential for downwind pesticide drift during the implement spray trials. Because localized application may be beneficial for pest control and drift reduction, the findings indicate a strong potential for "spot" or "band" spray coverage using UAV methods. This is likely due to the smaller size, reduced spray volumes, and increased agility of UAVs as compared to more conventional methods.

Nanoparticle collection efficiency of capillary pore membrane filters.

The surface and overall collection efficiencies of capillary pore membrane filters were measured for sub-micrometer particles. Collection efficiencies were derived from the surface loadings of particles on filters measured by scanning electron microscopy and from airborne particle concentrations measured with a scanning mobility particle sizer. Tests used filters with nominal pore diameters of 0.4 and 0.8 µm and face velocities of 3.7 and 18.4 cm/s. Surface collection efficiencies were below 100% for particles smaller than 316 nm and below 55% for particles smaller than 100 nm. Overall collection efficiencies reached as low as 45% for 70 nm particles. For nanoparticles, collection efficiencies overall were substantially higher than those to the filter surface, indicating that deposition occurs to a large extent inside the filter pores. These results underscore the need to account for surface collection efficiency when deriving airborne concentrations from microscopic analysis of nanoparticles on capillary pore membrane filters.

Variable workup calls for guideline development for type 2A hereditary haemochromatosis.

BACKGROUND: Type 2A hereditary haemochromatosis (type 2A HH) is a rare iron-loading disorder caused by mutations in the HFE2 gene, which encodes the HJV protein. We present characteristics, treatment and follow-up of subjects diagnosed with type 2A HH in the Netherlands to increase awareness of the disease and its treatment, and to define knowledge gaps. METHODS: We collected clinical, biochemical and genetic data from seven patients (two female; five probands) from six families genetically diagnosed with type 2A HH at the Expertise Center for Iron Disorders, Radboud University Medical Centre between 2006 and 2016. RESULTS: The five probands presented with heterogeneous complaints between the ages of 19 and 39. One of two patients with delayed clinical diagnosis developed hypogonadism and Y. enterocolitica sepsis. Diagnostic workup and follow-up varied. When assessed, elevated transferrin saturation (79-98%), ferritin (1400-6200 µg/l) and severely elevated liver iron levels were found, and in all subjects, phlebotomies were initiated. One subject was switched to erythrocytapheresis. Target ferritin levels varied. Despite long-term iron depletion, two subjects developed clinical complications. Sanger sequencing revealed two pathogenic HFE2 variants (homozygous or compound heterozygous) for the five families of Dutch descent and one new pathogenic variant in the family of non-Dutch descent. CONCLUSION: Three genetic variants caused type 2A HH in six families. Clinical diagnosis was delayed in two subjects. We observed variance in presentation, workup, follow-up and treatment. We found new complications in long-term iron-depleted patients. We recommend research and guidelines for optimal workup, follow-up and treatment of type 2A HH.

TFR2-related haemochromatosis in the Netherlands: a cause of arthralgia in young adulthood.

BACKGROUND: Type 3 hereditary haemochromatosis (HH) is a rare iron overload disorder caused by variants in the transferrin 2 receptor (TFR2) gene. We aim to present characteristics of patients diagnosed with TFR2-HH in the Netherlands, in order to increase knowledge and awareness of this disease. METHODS: We collected clinical, biochemical and genetic data from four patients from three families diagnosed with HH type 3 in the Netherlands between 2009 and 2016. RESULTS: Three women and one man diagnosed with HH type 3 presented with arthralgia and elevated ferritin levels and transferrin saturation (TSAT) at ages 25-41 years. The hepcidin/ferritin ratio as measured in three patients was low. Liver iron content in two patients as assessed by MRI or liver biopsy was highly increased (250 and 362.7 µmol iron/g dry weight, respectively, reference < 35 µmol/g). DNA analysis revealed four different TFR2 pathogenic variants: one nonsense, one splicing and two missense variants, of which three are novel. Phlebotomy decreased the serum iron parameters but did not relieve the arthralgia. CONCLUSION: In patients with a combination of elevated TSAT and ferritin in the absence of anaemia, and after exclusion of HFE-related HH, rare forms of HH should be considered. In these cases, presentation with arthralgia in young adulthood, low hepcidin/ferritin ratio and/or liver iron content > 100 µmol/g form an indication for analysis of the TFR2 gene. Although type 3 HH is extremely rare, awareness of the disease among physicians is important in order to achieve an early diagnosis and prevent complications, such as liver damage.

Genetic diversity in the Helicobacter pylori cag pathogenicity island and effect on expression of anti-CagA serum antibody in UK patients with dyspepsia.

AIMS: To investigate variation within the cag pathogenicity island (PAI) of Helicobacter pylori isolated from patients with dyspepsia in mid-Essex, and to evaluate the effect on expression of anti-CagA antibody. METHODS: Sixty two isolates of H pylori cultured from gastric biopsies were screened by specific PCR assays for the presence of cagA and other gene markers (cagD and cagE, and virD4) in the cag PAI. An enzyme linked immunosorbent assay (ELISA) kit (Viva Diagnostica helicobacter p120) was used to test for anti-CagA IgG antibody in matching sera. Isolates were also genotyped by vacuolating cytotoxin polymerase chain reaction (PCR) analysis, and tested for absence of the complete cag PAI (empty site PCR assay). RESULTS: Forty one of the H pylori isolates had a cag PAI containing cagA. One strain had no cagA but other cag PAI loci were present, whereas the remaining 20 strains had no detectable cag PAI markers. Anti-CagA IgG antibody was detected in 34 sera by the ELISA assay, and when compared with the cag PAI genotype of the infecting strain, accuracy, sensitivity, and specificity were 92%, 87%, and 100%, respectively. The seven discrepant or borderline strains in the ELISA were all vacA s1 but differed in other genotypic markers. CONCLUSIONS: The cag PAI was widely distributed in H pylori from patients with dyspepsia in mid-Essex who had different gastric pathologies. Infection with a strain having an uninterrupted cag PAI was associated with the presence of anti-CagA antibody in most patients. Discrepant ELISA results, mostly for elderly patients with duodenal ulcers, were attributed to cagA associated variation, particularly to the presence of mixed cagA+/cagA- cell variants in the infecting strain population. Tests for anti-CagA serum antibody were unreliable for predicting severity of clinical disease associated with H pylori infection in this series of patients.

Molecular epidemiology of Helicobacter pylori in England: prevalence of cag pathogenicity island markers and IS605 presence in relation to patient age and severity of gastric disease.

The cagA gene is a key marker for the Helicobacter pylori cag pathogenicity island (PAI), which may vary in composition in different strains with insertion sequence mediated interruptions and deletions of genes. While presence of cagA has been associated with increased risk for peptic ulcer disease and gastric cancer, the precise link with virulence is controversial. We investigated H. pylori from dyspeptics in one location in England (mid-Essex) with reference to the prevalence and distribution by age cohort of different cag PAI forms to determine if presence of the insertion element IS605 had a modifying effect on the severity of associated disease. H. pylori isolated from gastric biopsies over a 4-year period were screened by specific PCR assays for the presence of cagA, cagD, cagE and virD4 genes in the cag PAI, and for the presence of IS605 in the PAI and elsewhere in the genome. Most (68%) of the 166 isolates of H. pylori contained a PAI based on detection of cagA whereas 29% had no detectable PAI using multiple loci. The cagA+ genotype frequencies were similar in the peptic ulcer and non-ulcer dyspepsia-gastritis groups (79% vs. 74%) whereas frequencies in the NUD-oesophagitis and normal mucosa groups were lower (58%) but not significantly different (P>0.41). Genomic IS605 inserts were present at an overall frequency of 32% and were widely distributed with respect to patient age and disease severity. The combined cagA+/IS- strain genotype was common but not significantly associated with PUD compared to endoscopically normal mucosa (P> or =0.807). We concluded that presence of the IS605 element, whether in cagA+ or cagA- strains of H. pylori, did not systematically modify the severity of associated disease in the study population.

Bilateral thalamic glioma: review of eight cases with personality change and mental deterioration.

PURPOSE: To describe the clinical, radiographic, and neuropathologic features of bilateral thalamic glioma. METHODS: We searched our hospital records (1963 to present) to identify patients diagnosed as having the disease. RESULTS: Our search revealed eight patients, ranging in age from 8-63 years, with bithalamic tumor diagnosed by angiography, CT, and/or MR. All patients displayed personality changes and/or mental deterioration, including memory loss, inattention, confusion, hallucination, hyperphagia, or slow mentation. Unilateral motor weakness was also noted in six cases. The tumor always involved the medial aspect of the left and right thalami, but was often more extensive. The pathology was determined to be grades I-IV astrocytoma, confirmed by stereotactic biopsy or autopsy in six. Mild to moderate hydrocephaly occurred in some cases and was considered to be a contributing factor to mental deterioration. No correlation was found between age and type of tumor. CONCLUSIONS: Bilateral glioma of the dorsomedial and intralaminar nuclei of the thalamus can be a primary cause of dementia that has not been well-recognized in the past. CT and particularly MR should be considered for patients presenting with personality change or dementia, because of the possible presence of this unusual but devastating disease.

Stereoscopic digital subtraction angiography in neuroradiologic assessment.

Digital subtraction angiography (DSA) with stereoscopic imaging was performed in 40 patients for evaluation of a variety of cerebrospinal disorders. It was facilitated by a C-arm mounted x-ray tube and imaging chain with 7 degrees angulation between image pairs. Stereoscopic digital imaging proved particularly useful in the preoperative assessment of aneurysms, arteriovenous malformations, and primary and metastatic tumors. The technique was also found to be useful as a real-time adjunct to therapeutic radiographic procedures, as an aid in stereotaxic procedures, and in follow-up of postsurgical patients. Although the intravenous route was occasionally used, especially in postoperative follow-up of aneurysms, the procedure was most often carried out via an intraarterial approach. Stereoscopy was useful in supplying depth information regarding the relations between lesions and surrounding normal and abnormal vasculature. This technique combines the demonstrated advantages of intraarterial DSA with the unique advantage of stereoscopic imaging to demonstrate three-dimensional detail, thus contributing significantly to diagnostic confidence. Disadvantages are discussed. Further refinements in the equipment are expected: generation of stereo images with one injection, thus increasing procedure efficiency and patient safety; a video stereoscopic viewing unit; and the ability to obtain precise measurements via computer of depth, position, distance between, and true size of objects.

Three-dimensional reconstruction of vascular trees. Theory and methodology.

In this paper we examine the few-view reconstruction problem as it applies to imaging vascular trees. A fully automated reconstruction algorithm is described that circumvents the traditional "correspondence problem," using only notions of consistency and connectivity. It is assumed that the vascular tree is a connected structure and that its centerlines have been identified in three or more images. The first of three steps in the procedure involves generating a connected structure that represents the multiplicity of solutions that are consistent with any two (different) projections. The second step assigns to each branch in this structure a measure of agreement based on its relationship with one or more additional views of the vasculature. The problem then becomes one of propagating this information, via connectivity relationships and consistency checks, throughout the above structure to distinguish between the branches comprising the imaged structure and the accompanying artifacts. In this paper we present the theory and methodology of the technique, while in a companion paper we address the issue of validation via simulations and experiments. Together, these papers shed some light on why ambiguities arise and often lead to errors in the few-view reconstruction problem. Strategies to handle these errors are described and results are presented that demonstrate the ability to obtain adequate reconstructions with as few as three distinct views.

Three-dimensional reconstruction of vascular trees: experimental evaluation.

This paper is the second of two that together present a novel approach to the problem of reconstructing vascular trees from a small number of projections. Previously, we described the reconstruction algorithm and how it effectively circumvents the matching or "correspondence problem" found in most photogrammetric or computer-vision-based approaches. The algorithm is fully automatic and assumes that the imaging geometry is known, the vascular tree is a connected structure, and that its center-lines have been identified in three or more images. It employs consistency and connectivity constraints and comprises three steps: The first generates a connected structure representing the multiplicity of solutions that are consistent with the first two views; the second assigns a measure of agreement to each branch in this structure based on one or more additional projections; and the third step employs this measure to distinguish between those branches comprising the vasculature and the accompanying artifacts. This paper addresses the issue of validation via simulations and experiments. In addition to a clinical case, we examine the performance of the algorithm when applied to simulated projections of two 3-D vascular models, both representative of the complexity faced in coronary and cerebral angiography. The results in each instance are impressive and demonstrate that adequate reconstructions may be obtained with as few as three distinct views.

Analysis of projection geometry for few-view reconstruction of sparse objects.

In this paper certain projections are examined as to why they are better than others when used to reconstruct sparse objects from a small number of projections. At the heart of this discussion is the notion of "consistency," which is defined as the agreement between the object's 3-D structure and its appearance in each image. It is hypothesized that after two or more projections have been obtained, it is possible to predict how well as subsequent view will perform in terms of resolving ambiguities in the object reconstructed from only the first few views. The prediction is based on a step where views of the partial reconstruction are simulated and the use of consistency to estimate the effectiveness of a given projection is exploited. Here some freedom is presumed to acquire arbitrary as opposed to predetermined views of the object. The principles underlying this approach are outlined, and experiments are performed to illustrate its use in reconstructing a realistic 3-D model. Reflecting an interest in reconstructing cerebral vasculature from angiographic projections, the experiments employ simulations based on a 3-D wireframe model derived from an internal carotid arteriogram. It is found that for such an object, the predictions can be improved significantly by introducing a correction to account for the degree to which the object possesses some symmetry in shape. For objects sufficiently sparse, this correction is less important. It is concluded that when the number of projections is limited, it may be possible to favorably affect the reconstruction process in this manner.

Intraoperative ultrasound for guidance and tissue shift correction in image-guided neurosurgery.

We present a surgical guidance system that incorporates pre-operative image information (e.g., MRI) with intraoperative ultrasound (US) imaging to detect and correct for brain tissue deformation during image-guided neurosurgery (IGNS). Many interactive IGNS implementations employ pre-operative images as a guide to the surgeons throughout the procedure. However, when a craniotomy is involved, tissue movement during a procedure can be a significant source of error in these systems. By incorporating intraoperative US imaging, the target volume can be scanned at any time, and two-dimensional US images may be compared directly to the corresponding slice from the pre-operative image. Homologous points may be mapped from the intraoperative to the pre-operative image space with an accuracy of better than 2 mm, enabling the surgeon to use this information to assess the accuracy of the guidance system along with the progress of the procedure (e.g., extent of lesion removal) at any time during the operation. Anatomical features may be identified on both the pre-operative and intraoperative images and used to generate a deformation map, which can be used to warp the pre-operative image to match the intraoperative US image. System validation is achieved using a deformable multi-modality imaging phantom, and preliminary clinical results are presented.

Dose distributions in dynamic stereotactic radiosurgery.

A treatment planning technique for calculation of dose distributions in dynamic stereotactic "radiosurgery" with a 10-MV isocentrically mounted linear accelerator is presented. The treatment planning for dynamic radiosurgery is a three-dimensional problem, since during treatment both the gantry and the couch rotate simultaneously, the gantry from 30 degrees to 330 degrees and the couch from 75 degrees to - 75 degrees. The patient surface and anatomical information is obtained from a family of computed tomography or magnetic resonance scans, and a stereotactic frame is used for target localization, treatment setup, and patient immobilization during the treatment. The dose calculational algorithm follows the gantry and couch rotation in an incremental fashion, and relies on measured stationary beam central axis percentage depth doses and dose profiles to calculate the normalized tissue-maximum-ratio distributions over a matrix of points defined on one of three orthogonal planes (transverse, sagittal, or coronal). The dose calculation algorithm is discussed in detail and calculated dose distributions for single plane and dynamic radiosurgery compared with measured data.

Multimodality image integration for stereotactic surgical planning.

A method is presented for integrating stereotactic projection and tomographic image data to give composite 3-D images (stereo pairs) of cerebral anatomy and vasculature. The technique serves to combine complementary information from each modality and allows the imaged volume to be viewed directly. The procedure is largely automated and requires no additional apparatus or information beyond that which is ordinarily employed during stereotactic surgical planning. The two types of data are combined by superimposing the projection angiogram (DSA) onto a translucent volume rendered CT or MR image. Since the rendering algorithm employs an orthographic projection technique, the tomographic volume must first be reshaped and oriented to yield a perspective view that matches the DSA projection. During this process, the data undergo various interpolations which consequently affect the accuracy of target identification based on the resulting images. The integrity of the matching procedure was assessed using simulated data sets. Also, calculations were performed to estimate the resolution of measurements made from digitized stereoscopic images. The resulting sub-pixel accuracy of the matched images suggests that the technique has potential for stereotactic applications. Preliminary results are presented illustrating combined CT-DSA and MR-DSA data sets.