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Diabetes management presents a substantial burden to individuals living with the condition and their families, healthcare professionals, and healthcare systems. Although an increasing number of digital tools are available to assist with tasks such as blood glucose monitoring and insulin dose calculation, multiple persistent barriers continue to prevent their optimal use.As a guide to creating an equitable connected digital diabetes ecosystem, we propose a roadmap with key milestones that need to be achieved along the way.During the Coronavirus 2019 pandemic, there was an increased use of digital tools to support diabetes care, but at the same time, the pandemic also highlighted problems of inequities in access to and use of these same technologies. Based on these observations, a connected diabetes ecosystem should incorporate and optimize the use of existing treatments and technologies, integrate tasks such as glucose monitoring, data analysis, and insulin dose calculations, and lead to improved and equitable health outcomes.Development of this ecosystem will require overcoming multiple obstacles, including interoperability and data security concerns. However, an integrated system would optimize existing devices, technologies and treatments to improve help to improve outcomes.

Summary: Background: There is minimal experience in continuous glucose monitoring (CGM) among underserved racial/ethnic minority populations with or at risk of type 2 diabetes (T2D), and therefore a lack of CGM-driven insight for these individuals. We analyzed breakfast-related CGM profiles of free-living, predominantly Hispanic/Latino individuals at-risk of T2D, with pre-T2D, or with non-insulin treated T2D. Methods: Starting February 2019, 119 participants in Santa Barbara, CA, USA, (93 female, 87% Hispanic/Latino [predominantly Mexican-American], age 54·4 [±12·1] years), stratified by HbA1c levels into (i) at-risk of T2D, (ii) with pre-T2D, and (iii) with non-insulin treated T2D, wore blinded CGMs for two weeks. We compared valid CGM profiles from 106 of these participants representing glucose response to breakfast using four parameters. Findings: A “northeast drift” was observed in breakfast glucose responses comparing at-risk to pre-T2D to T2D participants. T2D participants had a significantly higher pre-breakfast glucose level, glucose rise, glucose incremental area under the curve (all p

Thermal creep properties of Zr-Excel alloy (Zr-3.5 wt% Sn-0.8 wt% Nb-0.8 wt% Mo) have been investigated in this study. The limits of existing experimental data on the current material and the search for more isotropic properties in Pressure Tube (PT) material motivates the current study. Heat-treatment on Excel PT materials leads to significant microstructural changes, where a strong texture of the As-Received (ASR) PT materials has been altered to a different degree of randomness at various solution temperatures. Microstructural alteration through heat-treatments should have an influence on the thermal creep behavior of the current material. It is observed that at a relatively high creep test temperature (>300 °C), steady-state creep rate of both ASR and heat-treated materials depends on the applied stress in a power law fashion and approaches stress exponent value of ~3. However, at a relatively low test temperature, n showed a high value in all treatments. The activation energy ( Q ) for the creep mechanism has been found to be microstructure-dependent. The ASR material has a Q value of ~73 to ~114 kJ/mol at the applied test temperature range (150–350 °C). However, martensitic structure formation and other microscopic changes (dislocation structures and elemental segregation) caused significant increase in Q values up to ~325 kJ/mol in the heat-treated materials. A significant decrease has been observed in creep anisotropy in the WQ-895 treatment for which texture has been moderately randomized.

This paper presents a detailed microstructural characterization by EBSD and TEM techniques of a hydride blister grown on a Zircaloy-4 plate. The hydrides formed are found to be of δ-type, and exhibit an increasing volume fraction from alloy matrix, across matrix-blister boundary, and into the blister. The microstructure of the blister mainly consists of δ-hydride platelets, however there is still un-transformed α-Zr phase inside the blister. The orientation relationship between the hydride and alloy matrix has been analyzed. In addition to the commonly observed ( 0001 ) α − Z r / / { 111 } δ orientation relationship, we found hydrides with a secondary ( 0001 ) α − Z r / / ( 100 ) δ orientation relationship. A correlation was drawn between the formation of hydrides with the two orientation relationships and the parent grain orientation. TEM observation revealed the distribution of the remnant α-Zr phase inside the blister, which had either a nodular shape or appeared as thin nano-sized layers among the hydride platelets. The microstructure of the hydrides has been characterized by HRTEM, exhibiting a uniform atomic structure with high dislocation density. Lastly, δ-hydride embryos obeying the primary orientation relationship were found within untransformed α-grains, indicating a consistent nucleation mechanism during blister growth.

People with type 1 diabetes are at risk for early- and late-onset hypoglycemia following exercise. Reducing this risk may be possible with strategic modifications in carbohydrate intake and insulin use. We examined the exercise preparations and management techniques used by individuals with type 1 diabetes before and after physical activity and sought to determine whether use of differing diabetes technologies affects these health-related behaviours.We studied 502 adults from the Type 1 Diabetes Exchange's online patient community, Glu, who had completed an online survey focused on diabetes self-management and exercise.Many respondents reported increasing carbohydrate intake before (79%) and after (66%) exercise as well as decreasing their meal boluses before (53%) and after (46%) exercise. Most reported adhering to a target glucose level before starting exercise (77%). Despite these accommodations, the majority reported low blood glucose (BG) levels after exercise (70%). The majority of users of both insulin pump therapy (CSII) and continuous glucose monitoring (CGM) (Combined) reported reducing basal insulin around exercise (55%), with fewer participants adjusting basal insulin when using other devices (SMBG only = 20%; CGM = 34%; CSII = 42%; p0.001). However, CSII and Combined users reported that exercise makes their BG levels harder to control (p0.05) and makes them feel less able to predict their BG levels while exercising (p0.001); they show agreement that fear of low BG levels keeps them from exercising (p0.01).These findings highlight the need for exercise-management strategies tailored to individuals' overall diabetes management, for despite making exercise-specific adjustments for care, many people with type 1 diabetes still report significant difficulties with BG control when it comes to exercise.

Background: Continuous glucose monitoring (CGM) has demonstrable benefits for people living with diabetes, but the supporting evidence is almost exclusively from White individuals with type 1 diabetes. Here, we have quantified CGM profiles in Hispanic/Latino adults with or at-risk of non-insulin treated type 2 diabetes (T2D). Methods: 100 participants (79 female, 86% Hispanic/Latino [predominantly Mexican], age 54·6 [±12·0] years) stratified into (i) at risk of T2D, (ii) with pre-diabetes (pre-T2D), and (iii) with non-insulin treated T2D, wore blinded CGMs for 2 weeks. Beyond standardized CGM measures (average glucose, glucose variability, time in 70–140 mg/dL and 70–180 mg/dL ranges), we also examined additional CGM measures based on the time of day. Findings: Standardized CGM measures were significantly different for participants with T2D compared to at-risk and pre-T2D participants (p

People who use high-tech augmentative and alternative communication (AAC) solutions still face restrictions in terms of practical utilization of present AAC devices, especially when speech impairment is compounded with motor disabilities. This study aims to explore an effective way to decode breathing patterns for AAC by the means of a breath activated dynamic air pressure detection system (DAPDS) and supervised machine learning (ML). The aim is to detect a user’s modulated breathing patterns (MBPs) and turn them into synthesized messages for conversation with the outside world. MBPs are processed using a one-nearest neighbor (1-NN) algorithm with variations of dynamic time warping (DTW) to produce synthesized machine spoken words (SMSW) at managed complexities and speeds. An ethical approved protocol was conducted with the participation of 25 healthy subjects to create a library of 1500 MBPs corresponding to four different classes. A mean systematic classification accuracy of 91.97 % was obtained using the current configuration. The implications from the study indicate that an improved AAC solution and speaking biometrics decoding could be undertaken in the future.

We show that if A is Z , O 2 , O ∞ , a UHF algebra of infinite type, or the tensor product of a UHF algebra of infinite type and O ∞ , then the conjugation action Aut ( A ) ↷ Aut ( A ) is generically turbulent for the point-norm topology. We moreover prove that if A is either (i) a separable C*-algebra which is stable under tensoring with Z or K , or (ii) a separable II 1 factor which is McDuff or a free product of II 1 factors, then the automorphisms of A are not classifiable up to conjugacy by countable structures.

This pilot study provides a preliminary assessment of the impact of genotype on acute innate immune pro-inflammatory, metabolic and endocrine responses to repeated lipopolysaccharide (LPS) administered to growing heifers. Heifers (n = 4/genotype) were from unselected (stable milk yield since 1964, UH) or contemporary (CH) Holstein cows that differed in milk yield (6200 vs 11,100 kg milk/305 d) or from contemporary Black Angus (CA) cows bred to contemporary Red Angus bulls. Heifers were challenged with iv administration of 0.5 μg LPS/kg body weight on day 1 (Challenge 1) and d 5 (Challenge 2) of study to assess endotoxin tolerance. Plasma was collected at -1, -0.5, 0, 1, 2, 3, 4, 6, 8, and 24 h relative to each LPS administration. Rectal body temperature (BT) was measured before each blood sampling and at 5 and 7 h. Data were analyzed by repeated measures with sampling time as the repeated effect. Each genotype had at least one pro-inflammatory response that indicated it might have a more robust response than the other genotypes. The CH heifers had a greater TNF-α response, UH heifers had greater IL-6 and XO responses and CA heifers had greater BT and SAA response to LPS than the other genotypes. There was a genotype by time by interaction as cortisol peaked earlier in CH and UH than in CA heifers. Glucose response was less in CA and insulin response was greater in CH heifers. Endotoxin tolerance to LPS was evident as pro-inflammatory, cortisol, glucose and insulin responses were less during Challenge 2 than during Challenge 1. Differences among genotypes during Challenge 1 were eliminated during Challenge 2 except for the greater SAA response in CA heifers and indicate the potential for differential impacts of genotype on the development of endotoxin tolerance. Specific reasons for these effects of genotype are not clear from these data but the results support the hypothesis for differential innate immune signaling among these bovine genotypes.

Let X be a real reflexive separable locally uniformly convex Banach space with locally uniformly convex dual space X ∗ . Let Q : H → X be a linear compact injection, according to Browder and Ton, such that Q ( H ) ¯ = X , where H is a real separable Hilbert space. A degree mapping d on X is constructed from the Nagumo degree d N A on H by d ( T + f , G , 0 ) ≔ lim t → 0 d N A ( I + 1 t Q ∗ ( T t + f ) Q , Q − 1 G , 0 ) , where G ⊂ X is open and bounded, T t is the resolvent ( T − 1 + t J − 1 ) − 1 of a strongly quasibounded maximal monotone operator T : X ⊃ D ( T ) → 2 X ∗ with 0 ∈ T ( 0 ) , and f : G ¯ → X ∗ is demicontinuous, bounded and of type ( S + ) . A “range of sums” result is also given, using the Skrypnik degree theory, in order to further exhibit the methodology of “elliptic super-regularization”.

259 adults with type 1 diabetes completed measure of anxiety, depression and diabetes specific distress, HbA1c from medical records. Anxiety not depression predicted HbA1c, this association was mediated by illness specific cognitions. Targeting illness specific cognitions may be more productive than treatment of general dysphoria in type 1 diabetes.

We develop a fine-scale local analysis of measure entropy and measure sequence entropy based on combinatorial independence. The concepts of measure IE-tuples and measure IN-tuples are introduced and studied in analogy with their counterparts in topological dynamics. Local characterizations of the Pinsker von Neumann algebra and its sequence entropy analogue are given in terms of combinatorial independence, l_1 geometry, and Voiculescu's completely positive approximation entropy. Among the novel features of our local study is the treatment of general discrete acting groups, with the structural assumption of amenability in the case of entropy., 44 pages

The antibacterial properties of bacteriophage lytic enzymes may be of importance in future mastitis control programs. A prophage was isolated from a strain of Streptococcus uberis (ATCC 700407) following exposure to mitomycin C. Partial sequencing of the phage DNA revealed a putative lysin based on sequence similarity to other streptococcal phage lysins. The putative lysin (Ply700) was recombinantly expressed in Escherichia coli, and chromatographically purified. Addition of the purified Ply700 to bacterial suspensions of S. uberis, Streptococcus pyogenes, and Streptococcus dysgalactiae caused a rapid, calcium-dependent lysis while there was little activity against Streptococcus agalactiae, Staphylococcus aureus, or E. coli. Killing of S. uberis in milk by Ply700 (50 microg/ml) was confirmed by plate count assay. Activity was related to the initial concentration of bacteria in that 31% killing (P

Glucose monitoring is important for patients with diabetes treated with insulin. Conventional glucose monitoring requires a blood sample, typically obtained by pricking the finger. A new sensor-based system called "flash glucose monitoring" monitors glucose levels with a sensor worn on the arm, without requiring blood samples.To estimate the utility difference between these two glucose monitoring approaches for use in cost-utility models.In time trade-off interviews, general population participants in the United Kingdom (London and Edinburgh) valued health states that were drafted and refined on the basis of literature, clinician input, and a pilot study. The health states had identical descriptions of diabetes and insulin treatment, differing only in glucose monitoring approach.A total of 209 participants completed the interviews (51.7% women; mean age = 42.1 years). Mean utilities were 0.851 ± 0.140 for conventional monitoring and 0.882 ± 0.121 for flash monitoring (significant difference between the mean utilities; t = 8.3; P0.0001). Of the 209 participants, 78 (37.3%) had a higher utility for flash monitoring, 2 (1.0%) had a higher utility for conventional monitoring, and 129 (61.7%) had the same utility for both health states.The flash glucose monitoring system was associated with a significantly greater utility than the conventional monitoring system. This difference may be useful in cost-utility models comparing the value of glucose monitoring devices for patients with diabetes. This study adds to the literature on treatment process utilities, suggesting that time trade-off methods may be used to quantify preferences among medical devices.

The early recurrence of atrial fibrillation (AF) after cardioversion and the need for frequent cardioversions to maintain sinus rhythm are important clinical features of AF management.We evaluated patients in the AFFIRM study whose qualifying episode of AF lastedor = 48 hours and was terminated by cardioversion. Clinical, electrocardiographic, and echocardiographic risk factors associated with AF recurrence within 2 months of cardioversion andor = 2 cardioversions during the first year were identified using multivariate analysis in 1293 eligible patients.The risk factors for the recurrence of AF within 2 months of cardioversion were no coronary artery disease and an electrocardiographic lead II P-wave duration of135 milliseconds. In the subset of patients not taking antiarrhythmic drug therapy, the multivariate risk factors were no coronary artery disease, second or greater episode of AF, left ventricular ejection fraction0.50, and mitral valve thickening. Significant risk factors for the need for2 cardioversions in the first year in patients taking antiarrhythmic medication were left atrial diameter4.5 cm and mitral valve thickening. The overall sensitivity and specificity of these parameters for recurrence and repeated cardioversion are low.There are several risk factors for difficulty maintaining sinus rhythm after cardioversion of persistent AF. The clinical predictive value of these factors is low, and they probably should not be used to justify withholding rhythm control efforts in patients who might benefit from sinus rhythm.

Summary Povidone-iodine solution is currently employed for pin-site care in many institutions. There are concerns that this agent reacts with the metal pins and can impede healing. This study compared two different treatment protocols for the care of the skin surrounding skeletal pin-sites. This practical clinical trial, employing stratified sampling, compared 10% cutaneous povidone-iodine solution with soft white paraffin ointment for the treatment of skeletal pin-sites. The end points of the study were the presence of clinical signs of pin-site inflammation and/or infection and pin removed as treatment was completed. Data were analysed on 116 pin-sites from 18 patients. Seventy-two pins (62%) were treated with povidone-iodine and 44 (37.9%) with paraffin ointment. The group treated with soft white paraffin ointment more frequently developed clinical signs of infection ( n =15; 34.1%) than the povidone-iodine treatment group ( n =13; 18.1%) ( χ 2 (df)=3.8(1); p =0.05). Also, 43.8% of pin-sites on the medial aspect of the lower leg displayed inflammation/infection compared with 16.7% of other lower limb pin-sites ( χ 2 (df)=9.28(1); p =0.002). The use of an antibacterial agent in the management of skeletal pin-sites reduces the likelihood of infection. Further studies are needed to determine whether anatomical position of the pin-site is a risk factor for the development of pin-site infection and whether intervention could reduce inflammation/infection at medial lower limb pin-sites.

Mammary gland epithelial cells are likely to be important effectors in defending against mastitis, yet little is known about their response mechanisms. Here, we describe a cryopreserved bovine mammary epithelial cell model to study the infection response. Primary cell cultures from four Holstein cows were prepared, and frozen after two passages. The cell cultures from each cow were then thawed and maintained separately, yet simultaneously, and exposed to treatments that included infection with Staphylococcus aureus or exposure to LPS from Escherichia coli. A clear inflammatory response was shown by a significant (P < 0.05), dose dependent, increase of lactoferrin and IL-8 secretion within 24h in response to S. aureus or LPS. Marked increases (P < 0.05) in lactoferrin, TNF-alpha and serum amyloid A (SAA) mRNA expression were also observed. The results indicate the usefulness of our model to study infection responses of mammary epithelial cells, where all cells are simultaneously exposed to the same infection pressure. These responses can be studied over time, and most importantly, biological replication is provided by the four different genotypes being investigated individually. Finally, the results indicate that mammary epithelial cells play an important role in inflammatory response, through the production of pro-inflammatory cytokines, an acute phase protein, and lactoferrin.

We develop a matricial version of Rieffel's Gromov–Hausdorff distance for compact quantum metric spaces within the setting of operator systems and unital C ∗ -algebras. Our approach yields a metric space of “isometric” unital complete order isomorphism classes of metrized operator systems which in many cases exhibits the same convergence properties as those in the quantum metric setting, as for example in Rieffel's approximation of the sphere by matrix algebras using Berezin quantization. Within the metric subspace of metrized unital C ∗ -algebras we establish the convergence of sequences which are Cauchy with respect to a larger Leibniz distance, and we also prove an analogue of the precompactness theorems of Gromov and Rieffel.

Transcranial Doppler (TCD) units measure blood velocity in the middle cerebral artery (MCA) and are used to examine the effects of pharmacological agents. The units actually measure the average of the maximum blood velocity envelope (aveV(max)) and it is assumed that changes in aveV(max) follow changes in the true mean velocity (aveV(mean)). This may not be true if there are changes in velocity profile. Results from previous TCD studies using acetazolamide (ACZ) and caffeine were examined for evidence for changes in velocity profile. ACZ increased aveV(max) by 21% (95% CI 13 to 29%) and aveV(mean) by 14% (95% CI 9 to 19%). Caffeine decreased aveV(max) by 8% (95% CI 4 to 12%) and aveV(mean) by 5% (95% CI 4% increase to 13% decrease). In both cases, the true change, measured using aveV(mean) was lower, indicating possible changes in velocity profile. We conclude that the possibility of changes in velocity profile must be considered when using TCD to quantify changes in blood velocity.

Followlng regular use, acute cessation of caffeine is associated with a characteristic withdrawal syndrome. Despite this, caffeine remains popular with its consumers. The aim of this study was to examine the physiologic and psychologic effects of small caffeine doses, administered in the form of a market-leading soft drink, on healthy women who were acutely withdrawn from caffeine. After 48-h abstinence and overnight fast, 11 healthy (22 to 40 years) female volunteers, all regular caffeine users (daily consumption 143 to 773 mg) consumed using a double-blind. randomized, controlled cross-over design either 2 tins of regular or caffeine-free Diet Coke. On both visits a Mars bar was eaten to prevent hypoglycaemia. Thus, the caffeine load was 76 or 10 mg respectively. Following ingestion of regular Diet Coke, there was a l0% fall in middle cerebral artery velocity (95% CI [6%-l4%], p < 0.005 versus caffeine free) and improvement in feelings of pleasure (p < 0.046) and energy (p < 0.037). Intellectual function (4-choice reaction time) was unaffected by caffeine status. On both visits, ingestion of Diet Coke induced a pressor response (maximum rise in systolic pressure +15+/- 2 mm Hg with caffeine and +l2 +/- 2 mm Hg with caffeine-free beverage, both p < 0.001 compared with baseline). In conclusion, in women acutely withdrawn from caffeine, ingestion of a popular soft beverage containing modest amounts of caffeine is associated with demonstrable physiologic and psychologic effects.

Keyhole laser welding of polymers is a subject well covered and researched, but relatively little information exists regarding the welding of thin polymer films, particularly to a heavier substrate. This paper presents the design of a suitable test apparatus for laser welding thin film to a heavier substrate, and shows the results of an investigation into the feasibility of laser welding multi-layer polymer film lids to tubs for the manufacture of aseptic food containers. A consistent weld, free from defects, is the key to process success. Typical welding defects have been synthesised in order to investigate, and consequently remove, their cause. The result is a reliable welding method based on even film clamping. With careful attention to machine design, a seal of high mechanical strength and chemical integrity is possible.

An optical pointing and tracking system incorporating opto-electronic components is described. The technique uses fast hardware based methods for tracking a beacon of laser light, where the focused spot is maintained in the centre of the TV camera image. The equipment was originally designed for use with a laser line-of-sight communication system for the control of a mobile vehicle, but can be easily used in many other tracking applications such as navigation, target acquisition and optical measurement systems. The system is designed to operate at short ranges from 1–20 m and has a positional accuracy of 0.1 mm or better at 10 m operating distance.

All the angiotensin peptides originate from angiotensinogen, a glycoprotein synthesized by several tissues, including the brain and the anterior pituitary. In the rat, immunohistochemistry has been used to localize angiotensinogen in gonadotropes and in uncharacterized cells surrounding sinusoids. Both cell types are capable of secreting angiotensinogen in cell culture; only the gonadotropes contain angiotensin II (AngII) and are capable of secreting it in culture. It has been asserted that the perisinusoidal cells are the only source of angiotensinogen for the generation of AngII by gonadotropes. Our current data favor the existence of a complete intracellular renin-angiotensin system (RAS) in gonadotropes and a separate extracellular system which utilizes the high concentration of angiotensinogen from perisinusoidal cells. Furthermore, we postulate that gonadotrope AngII serves mainly reproductive functions, while the proximity of angiotensinogen-secreting cells to folliculostellate cells, and their access to the intercellular sinusoidal and follicular spaces, places the extracellular RAS in a strategic position to affect pituitary growth and the mediation of acute-phase immune responses. In the rat brain, angiotensinogen is expressed by the 16-18th day of fetal life and by areas generally concerned with vasopressor, electrolyte, and fluid homeostasis. Antisense deoxyoligonucleotides to angiotensinogen mRNA lower blood pressure in hypertensive rats and inhibit in vitro growth of neuroblastoma cells, indicating a significant role for angiotensinogen in mitogenic and homeostatic functions. It is commonly agreed that astrocytes express angiotensinogen. Neuronal angiotensinogen has also been demonstrated by immunohistochemistry, as a secretion from neuronal cell cultures, and by reverse-transcriptase polymerase chain reaction. The fate of secreted astrocytic and neuronal angiotensinogen remains obscure. Angiotensinogen is regulated in a tissue-specific manner with smaller or absent responses observed for brain tissue. By using astrocyte and neuronal cultures the actions on angiotensinogen production of growth hormone, IGF-1, inflammatory lipopolysaccharide, and phorbol ester have been examined. Recent observations show that angiotensinogen is regulated positively or negatively by glucocorticoids and that a positive synergism between cAMP and glucocorticoids exists. On the basis of analogous systems for other proteins, a scheme involving glucocorticoid receptors, CREB, and AP-1 transcription factors is formulated to explain glucocorticoid-cAMP interactions. These transcriptional interactions may form a significant functional link between the RAS and adrenergic mechanisms.

Pulsed Electronic Speckle Pattern Interferometry (ESPI) offers the possibility of analysing fast transient phenomena in experimental mechanics. However, due to the short pulse separation required, addition fringes with very low visibility are generated. Several methods have recently been developed to process these data but they all suffer some limitations. This paper presents an electro-optical system based on the use of a Pockels cell which enables the introduction of carrier fringes between the firing of two consecutive laser pulses. This allows calculation of the wrapped phase distribution from a single fringe pattern using the Spatial Synchronous Detection method and enables the laser pulse separation to be significantly reduced. Preliminary experimental measurements performed using a continuous wave laser are used to illustrate the performance of this approach.

For the patient with diabetes, hypoglycaemia unawareness--ie, the warning signs of falling blood glucose are missing--is potentially dangerous. One study has suggested that, in healthy volunteers, caffeine might be a helpful treatment. Our study looked at two effects of caffeine ingestion (250 mg) on the brain--namely, a decrease in cerebral blood flow and an increase in brain glucose use--to see if the recognition of and physiological responses to hypoglycaemia were altered in patients with insulin-dependent diabetes mellitus (IDDM).12 patients were studied twice. A hyperinsulinaemic glucose clamp was used to maintain plasma glucose at 5 mmol/L for 90 min, followed by 60 min at 3.8 mmol/L, and then 2.8 mmol/L for a further hour. After 30 min at 5 mmol/L, patients consumed, in a double-blind, crossover design, 250 mg caffeine or matched placebo. We recorded middle cerebral artery velocity (VMCA), counterregulatory hormone levels, and cognitive function, and patients recorded hypoglycaemia symptoms on a visual analogue scale.Caffeine caused an immediate and sustained fall in VMCA of 10 cm/s, from 60 to 50 cm/s (95% CI -5 to -15 cm/s; p0.001). At a blood glucose of 3.8 mmol/L, plasma adrenaline levels were twice as high after caffeine than after placebo (difference 524 pmol/L). When glucose was lowered to 2.8 mmol/L, caffeine ingestion was associated with: greater awareness of hypoglycaemia in 9 patients, significantly more intense autonomic and neuroglycopenic symptoms, and higher levels of adrenaline, cortisol, and growth hormone. Cognitive function (latency of P300 evoked potentials) deteriorated to the same extent in both studies at this glucose level.The sustained fall in VMCA and augmented sympathoadrenal and symptomatic responses during moderate hypoglycaemia suggest caffeine as a potentially useful treatment for diabetic patients who have difficulty recognising the onset of hypoglycaemia.

In an effort to generate high titer colostrum for immunotherapy of cryptosporidiosis, a study was conducted to test the efficacy of immunizing sheep with recombinant plasmid DNA (pCMV-CP15/60) encoding epitopes of 15 and 60 kDa surface antigens of Cryptosporidium parvum sporozoites. The plasmid DNA was used to immunize preparturient ewes at three dose levels by jet-injection into either hind limb muscle (IM) or mammary tissue (IMAM). Regardless of route of injection, a dose-dependent anti-CP15/60 immunoglobulin response was observed in sera and colostrum from sheep immunized with pCMV-CP15/60 plasmid DNA. High titer antibody responses were observed in one of three animals per group receiving an IM injection of 100 or 1000 micrograms pCMV-CP15/60. IMAM immunization with 100 or 1000 micrograms pCMV-CP15/60 plasmid DNA elicited higher titer colostrum responses and more consistent serum responses compared to IM injections. A negligible serum and colostrum anti-CP15/60 response was observed in ewes injected IM with 10 micrograms pCMV-CP15/60 or 1000 micrograms control plasmid DNA. Immunoblotting of native C. parvum sporozoite/oocyst protein with hyperimmune serum and colostrum corroborated the increased titers against CP15/60 antigen. Serum and colostrum antibodies from pCMV-CP15/60-immunized sheep were eluted from native CP15 protein and bound a surface antigen of C. parvum sporozoites as indicated by indirect immunofluorescence staining.

This study has investigated adrenoceptor-mediated responses and beta-adrenoceptors in neonatal-onset hypothyroidism in rats. Four groups of adult rats were studied: controls, neonatal-onset uncorrected hypothyroidism (continuous oral methimazole treatment) and after chronic triiodothyronine (T3) replacement of these rats at either 25 or 100 micrograms/kg/day for 8 weeks beginning at 12 weeks of age. Hypothyroid rats were 61% smaller with an 18% decrease in heart rate; food and water intake were reduced to 43% and 52%, respectively; O2 consumption was reduced to 20% and rectal temperature was 2.9 degrees lower. T3 administration increased body weight to 60-62% of controls; metabolic changes were reversed; but tachycardia and cardiac hypertrophy (60-120% increases) resulted. The positive inotropic responses to the selective alpha 1-adrenoceptor agonist, phenylephrine, in left ventricular papillary muscles were abolished; the beta 1-adrenoceptor agonist, noradrenaline, was significantly less potent as an inotropic compound in isolated cardiac tissues from hypothyroid rats. The potency of phenylephrine to contract thoracic aortic rings was reduced in hypothyroid rats. These changes in alpha- and beta-adrenoceptor mediated responses were reversed by T3 administration. Both beta 1- and beta 2-adrenoceptor densities were increased in the hypothyroid left ventricle; T3 administration further increased beta 1-adrenoceptor density. We conclude that neonatal hypothyroidism produces pronounced physiological responses, changes in adrenoceptor-mediated responses and an increased ventricular beta 1-adrenoceptor density. T3 replacement reversed the changes in cardiac responses and metabolic parameters, except body weight, but produced cardiac symptoms of hyperthyroidism (tachycardia, hypertrophy as well as an increased beta 1-adrenoceptor density).

In this paper, the contrast enhancement produced by the subtraction of two sets of double pulse electronic speckle pattern interferometry (ESPI) addition fringes is investigated. It is shown that in most practical cases this process will produce a second set of interference fringes in addition to those which can be directly related to the vibration mode of interest. The formation of this second fringe pattern is explained by theory and computer simulation. Finally, the results are verified using an ESPI system with a pulsed Nd: YAG laser.

The effect of exogenous IGF-I on the reproductive performance of female rats was examined by infusing either recombinant human IGF-I (400 μg/d; n = 19) or vehicle (n = 18) over a four-day period (the time of one reproductive cycle) beginning on the day following estrus. The females were exposed to male rats one day after the infusions had commenced, and were euthanized 15 d later. There was no treatment effect on serum progesterone levels at this time or on the number of fetuses. Furthermore, the number of corpora lutea were not different between the IGF-I and vehicle infused groups (15.8 vs. 14.8; P=0.09). Total serum IGF-I concentrations, as determined with a polyclonal antiserum based RIA, were increased approximately three-fold in samples obtained 20 hr after commencing the IGF-I infusion. These samples were also analyzed for IGF-I with a monoclonal antibody based RIA previously shown to detect human, but not rat, IGF-I. By subtraction, the concentration of endogenous rat IGF-I was found to be approximately 60% higher in IGF-I - infused rats than in control rats. This increase was likely due to a reduced clearance rate of IGF-I from the circulation, caused by a marked induction of 42–46 kDa and 30–34 kDa IGF-I binding proteins observed in these samples with a ligand blot technique. The binding protein induction indicates that the infused IGF-I was bioactive. This induction may have attenuated the effects of IGF-I on ovarian function.

This study encourages the use of percutaneous FNB to diagnose and stage advanced lung cancer in patients with palpable metastases in supraclavicular lymph nodes or soft tissues. Percutaneous FNB of metastases is much easier to learn than transthoracic needle aspiration: the superficial target is anchored and sampled with multiple passes using a short needle grasped directly in the fingers. It is fast, accurate, economical and nearly free of risk and pain. The technique saves time and money because it is the only procedure needed by many patients with palpable disease in stage IIIB and IV. Bronchoscopy, transthoracic needle aspiration and open surgical biopsy thus can be avoided in most patients with palpable metastases. Prompt diagnosis by FNB of metastases speeds palliation for patients with urgent need. Tumor cell type from FNB correlated with cytologic findings from sputum samples, bronchoscopy specimens and autopsy results.