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Type 1 diabetes autoantibodies are directed against multiple antigens including: glutamic acid decarboxylase (GAD65), protein tyrosine phosphatase-like islet antigen 2 (IA2), insulin (IAA), and Zinc transporter 8 protein (ZnT8). The aim of our study was to determine if the presence or titer of ZnT8 antibodies (Ab) was predictive of clinical presentation at diagnosis or subsequent disease course.Between January 2003 and May 2019, 105 patients aged ≤21 years with a clinical diagnosis of T1DM had at least 1 autoantibody measured. Retrospective chart review was completed. At diagnosis, we evaluated BMI z-score, HbA1c, and the presence of DKA. Complications analyzed post-diagnosis included episodes of DKA, diagnosis of autoimmune (AI) disease, and the presence of vascular complications. We evaluated cumulative lifetime excess glucose as HbA1c AUC6%.71 patients were ZnT8-Ab(+) (68%), with 19 having low titer ZnT8-Ab and 52 high titer ZnT8-Ab. Follow-up ranged from 10 days to 15.7 years, (median 2.08 years). There were no differences in characteristics at disease onset or in subsequent follow up between those with and without ZnT8 Ab or those with high or low titers of ZnT8 Ab except for a small but statistically significant difference in cumulative excess glucose (HbA1c AUC6%) between those with low and high titers (p=0.0095).Our study adds to the limited literature on the effect of the presence and titer of ZnT8Ab in pediatric diabetes. The small effect of ZnT8-Ab titer on glucose excess as measured by HbA1c AUC warrants further study.

Objective To define liquid chromatography tandem mass spectrometry (LC-MS/MS)–based cutoff levels and panels of steroid hormones, to improve diagnosis of nonclassic congenital adrenal hyperplasia (NCCAH) and other partial enzyme defects in the adrenals. Design Prospective cohort analysis. Setting University hospital-based tertiary endocrine center. Patients One hundred and twenty-one healthy adults and 65 patients evaluated for possible NCCAH (validation cohort). Interventions The LC-MS/MS–determined cutoffs for 11 steroids (basal and cosyntropin-stimulated) were defined by 2.5% and 97.5% percentile in healthy subjects. Validation cohort was used for comparison. Main Outcome Measures Percentage of patients diagnosed with NCCAH among patients with polycystic ovary syndrome (PCOS)-like symptomatology. Evaluation of the defined LC-MS/MS–based cutoff levels for steroid hormones among this patient group. Results Of the 65 PCOS-like patients evaluated for possible NCCAH, 8 (12.5%) were discovered and genetically verified, and 2 had classic congenital adrenal hyperplasia. Cosyntropin-stimulated 17-hydroxyprogesterone (17OHP) showed the best diagnostic accuracy for NCCAH with an area under the curve of 0.95 (0.89–1.0 with a sensitivity of 86% and a specificity of 88%. In homozygote patients, 21-deoxycortisol and 17OHP levels were elevated, in heterozygote patients only 17OHP (basal or stimulated) was raised. Four healthy patients in the validation cohort had 17OHP above the basal cutoff. Conclusions The NCCAH syndrome is frequent in patients with suspected PCOS, and should be considered as a routine screening when assessing infertility. We suggest the use of serum steroid profiling, including 21-deoxycortisol, together with the cosyntropin stimulation test with 17OHP. Our data support a 17OHP cutoff of 8.5 nmol/L (2.8 ng/mL) 60 minutes after cosyntropin stimulation, when measured with LC-MS/MS, significantly lower than current European guidelines. publishedVersion

Neonatal diabetes mellitus (DM) is defined by the onset of persistent hyperglycemia within the first six months of life but may present up to 12 months of life. A gene mutation affecting pancreatic beta cells or synthesis/secretion of insulin is present in more than 80% of the children with neonatal diabetes. Neonatal DM can be transient, permanent, or be a component of a syndrome. Genetic testing is important as a specific genetic mutation can significantly alter the treatment and outcome. Patients with mutations of either KCNJ11 or ABCC8 that encode subunits of the KATP channel gene mutation can be managed with sulfonylurea oral therapy while patients with other genetic mutations require insulin treatment.

Congenital nephrotic syndrome (CNS) is a complex condition that requires multidisciplinary care. Hyperlipidemia is a characteristic feature with elevation of serum cholesterol and triglycerides. Little evidence is available to guide treatment of dyslipidemia in infants with CNS. We describe successful treatment of severe hypertriglyceridemia through dietary changes in a boy with CNS. A 9-day-old boy presented to the emergency department with lower extremity edema caused by deep venous thrombosis. Laboratory evaluation identified hypoalbuminemia, nephrotic-range proteinuria, and a pathogenic variant of the NPHS1 gene. The initial triglyceride concentration of 369 mg/dl increased to 3096 mg/dl by 5 weeks of age, when his diet consisted of breast milk. Refrigerated breast milk was skimmed by removing the top layer after allowing it to separate for 24 h. This process was repeated prior to use. Skimmed breast milk was supplemented with medium-chain triglyceride oil and an infant protein powder. After 2 days, the triglyceride concentration declined to 481 mg/dl and, by day 10, to 148 mg/dl. When breast milk supply decreased, a 1:1 ratio of skimmed maternal breast milk to an elemental, very low-fat formula was utilized. The triglyceride concentration remained below 400 mg/dl for the first year of life, except when skimmed breast milk was not available during hospitalization. Severe hypertriglyceridemia caused by CNS can present in the neonatal period and be difficult to manage. In our patient, skimmed maternal breast milk was successful in reducing the triglyceride concentration and should be considered a therapeutic option for children with hyperlipidemia caused by CNS.

Introduction: Type 1 diabetes specific autoantibodies are glutamic acid decarboxylase (GAD65), protein tyrosine phosphatase-like islet antigen 2 (IA2), insulin (IAA), and Zinc transporter 8 protein (ZnT8). The aim of our study was to determine if the presence of ZnT8 antibodies(Ab) was predictive of clinical presentation at diagnosis or subsequent disease course. Methods: Between January 2003 and May 2019, 105 patients aged ≤ 21 years with a clinical diagnosis of T1DM had at least 1 diabetes autoantibody measured. For subjects who had less than 4 autoantibodies analyzed initially, residual serum sample was retrieved, and remaining autoantibodies were analyzed. Retrospective chart review was completed. At diagnosis, we evaluated BMI z-score, HbA1c, and the presence and severity of DKA. Complications recorded post diagnosis included episodes of DKA, diagnosis of autoimmune (AI) disease, and the presence of vascular complications. Results: Of the 105 patients, 71 were ZnT8(+) (68%). When comparing ZnT8Ab(+) to (-) patients at diagnosis, there was no difference in age (p=0.94), BMI z-score (p=0.83) or presence of DKA (p=0.26). There was no difference in duration of follow up between ZnT8 Ab (+) and (-) groups (p=0.54). Over follow-up, (0.05-15.7 years), there was no difference in rates of DKA episodes (p=0.71). There were no macrovascular complications recorded and no difference in microvascular complications between the 2 groups (p=0.14). There were more AI conditions in the ZnT8Ab(+) group, 77% compared to 23% in ZnT8Ab(-), but this did not reach statistical significance (p=0.12). Conclusions: Our study, unlike others, suggests that the presence of ZnT8 Ab does not result in a difference in disease course at presentation. This study adds to the literature as it has follow up on patients. Over up to 15 years of follow-up, there is no difference in complications between those with and without ZnT8 Ab’s. This study should be validated with larger numbers and longer follow up. Disclosure A. R. Dahl: None. S. Jenkins: None. J. Zbacnik: None. J. Foster: None. S. Pittock: None.

Introduction Calcinosis cutis is a condition characterized by pathologic calcium deposition into superficial dermal skin layers. It is often associated with an autoimmune disease. However, it may also occur after minor localized trauma and infection. Description of Problem We report a case of lumbar epidural placement of labor analgesia in a parturient with severe dystrophic calcinosis cutis without apparent complications. Clinical Solution We recommend fastidious optimization of epidural placement conditions for all patients who may be at high risk for neuraxial anesthesia, including consideration of ultrasound use, use of an experienced anesthesia provider for neuraxial placement, and placement in early labor. Additionally, judicious discussion of risks, benefits, and alternatives when obtaining informed consent is critical, ideally with the patient identified for a comprehensive visit in a preoperative obstetric anesthesia clinic before delivery.

This article investigates how comedians with an immigrant background gain political relevance, taking two contemporary comedians from Norway and Sweden as cases. The study uses media's interpretive power as a way to explore Habermas’ ([1996]. Between Facts and Norms: Contributions to a Discourse Theory of Law and Democracy. Cambridge, MA: MIT Press) claim that the borders between the cultural and the political public spheres are porous. A reading of the press coverage of the comedians is used to discover patterns in how media interpreted the comedians as immigrant voices and as humourists. It is demonstrated how the comedians get moulded into certain positions through mass media interpretations, as well as explained where these interpretations come from historically. Furthermore, it is shown that the coverage of the two comedians to a large degree conformed to existing immigration discourse, challenging the view of comedy as a subversive force. acceptedVersion

Type 1 diabetes mellitus (T1DM) can occur at any age, the presence of diabetes related autoantibodies predicts increased risk of disease and supports an autoimmune etiology for T1DM. Since 2017, Mayo Clinic Laboratories has been offering a comprehensive type 1 diabetes autoantibody evaluation (DM1Eval) which includes testing for 4 autoantibodies targeting glutamic acid decarboxylase autoantibodies (GAD), protein tyrosine phosphatase-like islet antigen 2 (IA-2), insulin (IAA), and zinc transporter 8 protein (ZnT8). The aim of this study was to determine the frequency of individual antibodies and antibody clusters (2, 3 or 4) stratified into 4 ages groups (children 0-17, young adult 18-35, middle aged 36-55 and older >55 years). Over a 30 month period (June 2017-Nov 2019) the DM1Eval was performed on 6,446 samples. At least 1 autoantibody was found in 3596 (56%) of all samples: 68% of children, 49% of young adults, 40% of middle aged and 41% of older adults. In patients with at least 1 antibody positive, GAD 65 antibodies were the most common in all age groups followed by ZnT8 in those Autoantibody clusters of 3 or 4 antibodies were more frequently encountered in younger patients (41% of pediatric and 27% of young adult patients in contrast to just 12% in middle and older age groups). Disclosure A.R. Dahl: None. S. Pittock: None. A. McKeon: None. J. Foster: None. J. Mills: None.

A previously healthy 2-year old Hmong girl presented to the Emergency Department with first time seizures during a febrile illness. Seizures continued for the next two weeks despite multiple antiepileptic agents. All initial cultures and evaluations were negative, and febrile infection related epilepsy syndrome (FIRES) was diagnosed. Three weeks into her hospital course, the patient developed a morbilliform rash on her thigh that became generalized. Concurrently, she developed fever and tachycardia. Laboratory studies demonstrated eosinophilia, an increase in ALT, AST, and direct/total bilirubin. CMV, EBV, and HHV-6 were negative. Skin biopsy showed lichenoid interface dermatitis. Clinical picture was suggestive of drug reaction with eosinophilia and systemic symptoms (DRESS). Topical and systemic steroids were started. Potential triggers for DRESS were discontinued. The patient deteriorated and cardiorespiratory failure occurred. She required ECMO for eight days. Patient gradually improved over the following weeks despite recurrent seizures and remained in the hospital for 283 days. FIRES is a rare and highly morbid condition in which patients develop status epilepticus in the setting of febrile illness that is often intractable to anticonvulsants and steroids. Typically no causative infection is identified. DRESS, another rare and potentially fatal condition, is a drug hypersensitivity reaction that includes eosinophilia, characteristic skin findings and potential involvement of liver, lungs, kidneys, or other organs. Allopurinol, antiepileptic agents, and antibiotics are the most frequently reported triggers. In this case report, we describe a patient who developed DRESS following FIRES, a sequence not previously described in the literature.

BACKGROUND There is a lack of consensus on the cardiometabolic consequences of mild subclinical hypothyroidism (SCH) among children. The objective of the current study was to compare lipid profiles in children with mild SCH with those of euthyroid children. STUDY DESIGN Retrospective medical record review. PATIENTS Children (ages 2-18 years) who had undergone simultaneous measurement of TSH, free thyroxine (T4) and lipids. Lipids in children with mild SCH (TSH 5

Klinefelter syndrome is the most frequent chromosomal aneuploidy in males occurring in about 1 in 660 males. Epidemiological studies have demonstrated increased risk of type 1 diabetes and type 2 diabetes in adults with Klinefelter syndrome. There is only one previous report of neonatal diabetes in a patient with Klinefelter syndrome. We report transient neonatal diabetes due to a pathogenic heterozygous variant in KCNJ11 in a male infant with Klinefelter syndrome. A 78-day old male infant was noted to have sustained hyperglycemia with serum glucose ranging between 148 mg/dL (8.2 mmol/L) and 381 mg/dL (21.2 mmol/L) three days after undergoing a complete repair of an atrioventricular defect. Hemoglobin A1c was 6.6%. The patient was born at term with a birth weight of 2.16 kg following a pregnancy complicated by gestational diabetes that was controlled with diet. The patient was initially started on a continuous intravenous insulin drip and subsequently placed on subcutaneous insulin (glargine, human isophane and regular insulin). Insulin was gradually decreased and eventually discontinued at seven months of age. Chromosomal microarray at 11 weeks of age showed XXY and a panel-based, molecular test for neonatal diabetes revealed a pathogenic heterozygous variant c.685G>A (p.Glu229Lys) in KCNJ11. The patient is now 34 months old and continues to have normal fasting and post-prandial glucose and HbA1C levels. The patient will need prospective follow up for assessment of his glycemic status. To our knowledge this is the second reported case of neonatal diabetes in an infant with Klinefelter syndrome and the first due to a mutation in the KCNJ11 in a patient with Klinefelter syndrome.

Background Accumulation of contrast medium in the subdural space after diagnostic intraarterial and intravenous contrast administrations is a rare observation. The authors report the case of a subdural contrast effusion (SCE) mimicking an acute subdural hematoma (SDH) presenting during embolization of an intracranial dural arteriovenous fistula (DAVF). Clinical history A 52-year-old woman was admitted to our department with a four months history of left-sided numbness of the upper lip, cheek, tongue and forehead. Digital subtraction angiography showed a right tentorial DAVF with a venous ectasia. The DAVF was mainly supplied by the right middle meningeal artery, occipital artery and the artery of Bernasconi-Cassinari and drained into the Galenic venous system. Procedure The patient underwent endovascular treatment with triaxial catheterization of the right occipital artery. Transarterial embolization using PHIL was performed and monitored by control runs made with an intermediate (distal access) catheter. After several injections, increased accumulation of contrast medium along the cerebellar tentorium and the walls of both transverse sinuses was noted. An immediately performed Dyna CT showed extensive contrast medium in the subdural space of the posterior cranial fossa and foramen magnum suspicious for an acute SDH. The catheters were removed, and the procedure was terminated. The patient woke up presenting no new symptoms and had an uneventful postoperative course. A 24-hour follow-up Dyna CT was completely normal suggesting the diagnosis of an asymptomatic SCE. We believe that repeat high pressure contrast injections via a large bore intermediate catheter into the territory of a (even partly) occluded DAVF may have induced leakage of contrast medium into the extravascular subdural space thereby causing a SCE. Summary In conclusion we present the unique case of an asymptomatic SCE, which developed during transarterial embolization of a DAVF. SCE can occur during endovascular therapy and may mimic an acute SDH. Differentiation between the two by computed tomography or Dyna CT and early neurological examination can be crucial for patient management. Disclosures R. Dahl: None. V. Eskesen: None. G. Benndorf: None.

In this paper, political advertisements in Norway are characterized as an argumentative activity type, following the pragma-dialectal theory of argumentation. Drawing on insights from political theory, marketing theory, Norwegian media regulations and empirical research into Norwegian political communication the conventions of the activity type are discussed. It is also explained how these conventions influence the arguer’s strategic maneuvering.

Coherent lidar techniques by providing direct measurement of optical phase enables advanced techniques for long-range imaging, atmospheric turbulence measurements, and potentially imaging through turbulence without the use of adaptive optics.

Amendments to the Federal Rules of Civil Procedure (FRCP) will take effect on December 1, 2015 (the "2015 Amendments") unless Congress acts to modify or reject them, which is highly unlikely.1 Collectively, the changes are designed to lower the costs of litigation by 1) providing judicial tools to encourage and enforce proportional discovery limited to information relevant to "claims and defenses," and 2) reducing costs associated with over-preservation and ancillary litigation by establishing a uniform national standard for preservation obligations and a safe harbor for parties that take reasonable steps in good faith to preserve electronically stored information ("ESI").This article provides an overview of these and other key 2015 Amendments along with examples of analytical methodologies to help courts and lawyers apply the Amendments as envisioned and, where appropriate, providing context and support from existing cases and commentary.I. IntroductionThe Amendments embrace a number of measures stemming from the Duke Conference of May 2010, which was convened by the Advisory Committee on Civil Rules ("Rules Committee") to address persistent complaints about the costs of discovery (especially e-discovery), preservation of ESI and standards for sanctions for the destruction of such material.2 After the Conference, the two subcommittees assigned to respond (the "Duke" Subcommittee, for all rules other than Rule 37(e), and the "Discovery" Subcommittee for issues relating to spoliation) considered a number of potential rules and amendments through a transparent process in which public participation was deep and effective.This process included two "miniconferences" held before the Rules Committee released initial proposals in August, 2013, followed by three public hearings involving 120 testifying witnesses and over 2,300 written comments. After careful consideration of competing arguments and, in some cases, substantial revisions, the Rules Committee, the Judicial Conference and the Supreme Court unanimously approved the final package of amendments. Many of the surviving proposals can be traced to discussions at the Duke Conference and the proposals and submissions relating to it, such as the LCJ White Paper.* * 3The 2015 Amendments can have a dramatic impact if judges and lawyers implement them in the manner intended by the Rules Committee. They reflect the realities of current discovery and address many of the core issues not adequately treated in the 2006 Amendments.4 * More data exists now than any time in our history, a problem that a revised Rule 26(b) addresses by embedding proportionality principles in both the scope of discovery and in cost allocation. Moreover, the replacement for Rule 37(e) provides a uniform culpability standard, which rejects the focus on the loss of a few emails to justify sanctions (e.g. Pension Committed).The amendments reflect agreement among a diverse spectrum of stakeholders that the high costs and burdens of discovery, especially e-discovery, are skewing the U.S. civil justice system. Unrestrained e-discovery is inordinately costly.6 Not only does this provide perverse incentives for requesting parties to make unlimited demands (at the cost of producing parties), but the costs routinely force unfair settlements for reasons other than a lack of merits.Large majorities of the plaintiffs' and defense bars share the view that e-discovery demands (and the threat of sanctions) are abused.7 The Committee concluded after the Duke Conference that "excessive discovery occurs in a worrisome number of cases."8 A survey of the Association of Corporate Counsel administered by the Institute for the Advancement of the American Legal System ("IAALS")9 found that 80 percent of chief legal officers or general counsel disagree with the statement that "outcomes are driven more by the merits of the case than by litigation costs." As the American College of Trial Lawyers ("ACTL") put it in advance of the Duke Conference, "[ajlthough the civil justice system is not broken, it is in serious need of repair. …

DNA functionalisation is a proven route to program an assembly of nanoparticles into a vast array of nanostructures. In this paper, we used coarse-grained molecular dynamics simulations to study DNA-functionalised nanoparticles and demonstrate the effect of grafted DNA strand composition, specifically the placement and number of contiguous G/C bases in the grafted DNA single strands, on the thermodynamics and structure of nanoparticle assembly at varying grafting densities and particle sizes. At a constant G/C content, nanoparticles assemble more readily when the G/C bases are placed on the outer or middle portions of the strands than on the inner portion. In addition, the number of neighbours within the assembled cluster decreases as the placement of the G/C bases goes from the outer to middle to inner sections of the strand. As the G/C content decreases, the cluster dissociation temperature, Td, decreases, as the enthalpic drive to assemble decreases. At a high G/C content (number of grafts and G/C plac...

Flow instabilities driven by the dissipative nature of particle–particle interactions have been well documented in granular flows. The bulk of previous studies on such instabilities have considered the impact of inelastic dissipation only and shown that instabilities are enhanced with increased dissipation. The impact of frictional dissipation on the stability of grains in a homogeneous cooling system is studied in this work using molecular dynamics (MD) simulations and kinetic-theory-based predictions. Surprisingly, both MD simulations and theory indicate that high levels of friction actually attenuate instabilities relative to the frictionless case, whereas moderate levels enhance instabilities compared to frictionless systems, as expected. The mechanism responsible for this behaviour is identified as the coupling between rotational and translational motion. These results have implications not only for granular materials, but also more generally to flows with dissipative interactions between constituent particles – cohesive systems with agglomeration, multiphase flows with viscous dissipation, etc.

A 32-year-old man presented with severe abdominal pain and ascites. His medical history included diagnosis of Sandifer syndrome, scoliosis requiring 3 spinal surgeries, microgastria, and hiatal hernia repair, and most recently, laparoscopic cholecystectomy (7 weeks prior). Postprocedural abdominal pain led to a computed tomography (CT) 3 scan which confirmed ascites. The possibility of a postcholecystectomy common bile duct leak prompted an endoscopic retrograde cholangiopancreatography (ERCP) with stent placement. Unfortunately, this did not prevent peritoneal fluid from reaccumulating and the patient was transferred to our institution for further evaluation and management. The patient was afebrile and vital signs were normal. The abdominal examination revealed mild diffuse nonspecific tenderness. CT scan of abdomen was performed revealing increased peritoneal fluid. The radiologist noted that the findings were likely iatrogenic and could represent a bile, lymph, or pancreatic leak. CT guided paracentesis aspirated 280 mL of fluid accumulated near the right hepatic lobe and paracolic gutter. Aspirate was described as watery opaque and white with a pink tinge. Results of body fluid laboratory analyses are described in Table 1. View this table: Table 1. Body fluid testing laboratory results. Fluid accumulation after abdominal surgery could be the result of several etiologies. Definitive identification of the fluid source is critical to guide medical treatment. In this case, the increased amylase concentration in the fluid suggested pancreatic origin (1, 2). However, the aspiration of milky turbid fluid following paracentesis that contains a high concentration of triglycerides, as measured by a nonglycerol blanked assay, may lead the physician to include chylous ascites in the differential diagnoses. Chylous effusions are characterized by the presence of chyle in fluid accumulations in the pleural or peritoneal space following lymphatic obstruction or disruption (3). Chyle is composed of lymph and lipids suspended in chylomicrons, which are the largest lipid-carrying lipoprotein particles that carry mainly …

Additional file 1. IPCRG scaling up activities.

In order to remove the sulfur compounds in jet fuels to produce ultra-clean fuels e.g., for fuel cell applications in aircraft (auxiliary power units, APUs), an integrated desulfurization process was developed, which combines a fixed-bed adsorption with a membrane separation. The present study focuses on the optimizing the fixed-bed adsorption with an Al 2 O 3 -based adsorbent. A sulfur level of 10 ppmw is required by the fuel cell system. 1 g of the adsorbent is capable of processing 7.43 ml of a 50% (vol.) light fraction of Jet A-1 with 440 ppmw under optimum operating conditions. The maximum sulfur adsorption capacity is approximately 2.51 mg S/g of adsorbent. The sulfur-loaded adsorbent can be regenerated by air rather than by hydrogen-containing gasses at an elevated temperature of 500 °C. However, the regenerated adsorbent only maintains a stable cyclic capacity of 2.01 mg S/g-ads over 70 adsorption–desorption cycles. In addition, the adsorbent bed dimensions with regard to bed length, bed diameter and particle size were optimized to obtain the desired sulfur adsorption capacity without encountering a significant pressure drop across the adsorption column.

This paper investigates pervaporation, a membrane separation process for the removal of sulfur-containing components from jet fuel. To this end, one type of commercial membrane from PolyAn GmbH was applied. The influence of the crucial reaction parameters of the pervaporation process, such as feed temperature, permeate pressure, and permeate temperature, on the characteristic pervaporation measures such as permeate flux and enrichment factor was tested experimentally. Fuels with different sulfur mass fractions were applied and the long-term stability of the membranes used was studied. Different spectroscopic methods were applied to investigate correlations between membrane performance and material properties of the membrane. It was found that an increased feed temperature had a positive effect on the permeate flux while it had a negative effect on the enrichment factor. At 100 °C, the permeate flux amounted to 5.44 kg/(h m2), while it was only 1.16 kg/(h m2) at a feed temperature of 80 °C. At a feed temperature of 80 °C, the enrichment factor was 0.47, while it amounted to 0.64 at a feed temperature of 100 °C. In the case of the permeate pressure, the trends were also antagonistic. Low permeate pressure enhanced the permeate flux but deteriorated the enrichment factor. At a value of 20 mbar, the permeate flux amounted to 5.44 kg/(h m2), while it was only 0.16 kg/(h m2) at 100 mbar. The enrichment factor was 0.64 at 20 mbar and decreased to 0.35 at 100 mbar. Different permeate temperatures and sulfur mass proportions had only a minor effect on the permeate flux and the enrichment factor. Experiments on the long-term stability of the membranes used showed that fortunately the pervaporation process could be run for more than 500 h using membranes from PolyAn GmbH while still showing a measurable permeate flux and a remarkable reduction of the sulfur mass fraction in the permeate. However, a significant deactivation with time on stream was observed. The permeate flux continuously decreased from 3.5 kg/(h m2) to 0.5 kg/(h m2) after 532 h of time on stream. The enrichment factor increased from 0.5 to 0.6. Long-term experiments with pretreated membranes revealed that interaction between the hydrocarbon matrix in kerosene Jet A-1 and the membrane material itself was not responsible for the observed degradation of performance. Spectroscopic investigations were used to show that the reduction of the permeate flux was probably caused by an irreversible inclusion of polar – mostly aromatic – molecules in the polymeric separation layer of the membrane. The probable influence of unknown additives on the permeate flux could not be proven but should be considered. No degradation of the membrane material itself was found.

In recent years, there has been heightened awareness regarding the use of drugs to modify a person's behavior to facilitate crime. A drug rape case involving the potent, short-acting sedative triazolam will be presented. On three occasions, the victim consumed green tea and chocolate before being massaged and ultimately sexually abused. Screening for alcohol, commonly used drugs and illicit substances in blood and urine sampled during the forensic examination 20 h after the last incident, was negative. Consequently, hair samples for chemical analysis were taken from the assaulted individual 34 days after the last incidents. The hair was cut into three 2-cm segments (0-6 cm) that were washed, dissolved in extraction solvent and screened and verified by ultra performance liquid chromatography coupled with time of flight mass spectrometry (UPLC-TOF-MS) and with tandem mass spectrometry (UPLC-MS/MS), respectively. In the 2-cm hair segment corresponding to the period of the alleged assaults, the presence of the sedative triazolam was revealed at a concentration of 1.0 pg/mg hair. The preserved urine sample, taken 20 h after the last incident, was reanalyzed by UPLC-MS/MS for metabolites of triazolam, and 39 μg/l α-hydroxytriazolam was detected in the hydrolyzed urine. This case illustrates that hair is a valuable forensic specimen in situations where natural processes have eliminated the drug from typical biological specimens due to delays in the crime being reported. Furthermore, it was possible to verify the hair finding with a urine sample by detection of a metabolite of triazolam.

Two inbred mouse strains, CBA/J and CBA/CaJ, have been used nearly interchangeably as 'good hearing' standards for research in hearing and deafness. We recently reported, however, that these two strains diverge after 1 year of age, such that CBA/CaJ mice show more rapid elevation of compound action potential (CAP) thresholds at high frequencies (Ohlemiller, Brain Res. 1277: 70-83, 2009). One contributor is progressive decline in endocochlear potential (EP) that appears only in CBA/CaJ. Here, we explore the cellular bases of threshold and EP disparities in old CBA/J and CBA/CaJ mice. Among the major findings, both strains exhibit a characteristic age (∼18 months in CBA/J and 24 months in CBA/CaJ) when females overtake males in sensitivity decline. Strain differences in progression of hearing loss are not due to greater hair cell loss in CBA/CaJ, but instead appear to reflect greater neuronal loss, plus more pronounced changes in the lateral wall, leading to EP decline. While both male and female CBA/CaJ show these pathologies, they are more pronounced in females. A novel feature that differed sharply by strain was moderate loss of outer sulcus cells (or 'root' cells) in spiral ligament of the upper basal turn in old CBA/CaJ mice, giving rise to deep indentations and void spaces in the ligament. We conclude that CBA/CaJ mice differ both quantitatively and qualitatively from CBA/J in age-related cochlear pathology, and model different types of presbycusis.

A coherent downconverting microwave photonic link using balanced heterodyne detection of single-sideband modulated optical signals is analyzed and demonstrated. The intermodulation analysis shows that the second-order photodetector nonlinearity can be the limiting factor in the third-order intermodulation spur performance. The link is designed to phase coherently downconvert 17 GHz of bandwidth in an extended K-band (23–45 GHz) to 1–18 GHz to match the capabilities of modern receivers. The application of the link is for a low-loss >20 μs analog buffer. Spur performance of 112.4 dB/Hz(2/3) is demonstrated when background noise is limited by shot noise.

92 patients with acute myeloid leukemia were classified according to the FAB classification (M1 n = 20, M2 n = 43, M3 n = 1, M4 n = 19, M5a n = 2, M5b n = 2, and M6 n = 5 patients). Serum measurements of lactoferrin (LF), myeloperoxidase (MPO) and lysozyme (LYS) were performed before the start of treatment. LF was significantly lower in M1 when compared with M2 but not as compared to M4, MPO was significantly higher in M2 and M4 than in M1, but comparable MPO levels were found in M2 and M4. LYS was significantly elevated in M2 in comparison with M1, and in M4 when compared to both M1 and M2. Polymorphonuclear granulocytes (PMNs) in M1 were significantly reduced when compared with M2 and M4, whereas mononuclear cells were significantly increased in M4 in comparison with both M1 and M2. FAB classification did not generate any prognostic information. When the patients were, instead, subdivided according to LF levels we found prognostically significant differences. Of patients below 100 μg/1, 44% went into remission as compared to 77% with LF from 101 to 400 μg/1. In patients with LF levels above 400 μg/1 the remission frequency was only 14%. Multivariate statistical analysis on the data further suggested that lactoferrin may be used as an independent prognostic indicator. We conclude that although determination of the serum-levels of lactoferrin, lysozyme and myeloperoxidase in certain cases may be valuable as a supplement to the morphological examination of acute myeloid leukemia, it is evident that none of the three determinations can be used alone to distinguish between the FAB groups. However, we suggest that lactoferrin may be used as a prognostic indicator and may even be used to recognize a new variant of AML with a particularly poor prognosis -high lactoferrin AML.

This report provides a summary of deliberations conducted under the charge for members of Module A participating in the Naphthalene State-of-the-Science Symposium (NS3), Monterey, CA, October 9-12, 2006. Whole animal bioassays have been performed by the National Toxicology Program in mice and rats to ascertain the carcinogenic potential of naphthalene by inhalation exposure. A statistically significant increased incidence of pulmonary alveolar/bronchiolar adenoma (a benign lesion), was observed among female mice; an observed increase among the males did not reach statistical significance. No nasal tumors were observed in either sex. A tumorigenic response was observed in both sexes of rats, in males an increased incidence of nasal respiratory epithelium adenoma (a benign rather than malignant lesion) and in females, olfactory epithelial neuroblastoma. Interpretations of these studies vary. On the one hand, evidence of extensive non-neoplastic response in both sexes of both species indicates cytotoxicity occurred at all doses, and strongly suggests that cytotoxicity played a significant role in the tumor responses observed in the target tissues. On the other hand, olfactory epithelial neuroblastoma has rarely been observed in NTP bioassays. This review seeks to develop a consensus understanding of the scientific evidence provided by these studies, taking into account that they have been used as the basis for quantitative human cancer risk assessment, and suggests scientific studies that, if performed, could resolve scientific uncertainties.

Hundreds of millions of people of all ages suffer from chronic respiratory diseases which include asthma and respiratory allergies, chronic obstructive pulmonary disease, occupational lung diseases and pulmonary hypertension. More than 500 million patients live in developing countries or in deprived populations. Chronic respiratory diseases are increasing in prevalence. Although the cost of inaction is clear and unacceptable, chronic respiratory diseases and their risk factors receive insufficient attention from the healthcare community, government officials, media, patients and families. The Fifty-Third World Health Assembly recognised the enormous human suffering caused by chronic diseases and requested the World Health Organization (WHO) Director General to give priority to the prevention and control of chronic diseases, with special emphasis on developing countries. This led to the formation of the WHO Global Alliance against Chronic Respiratory Diseases (GARD). GARD is a voluntary alliance of organisations, institutions and agencies working towards a common vision to improve global lung health according to local needs. GARD is developed in a stepwise approach using the following three planning steps: estimate population need and advocate action; formulate and adopt policy; and identify policy implementation steps.

Mixture formation plays an important role in the diesel reforming process. It is important to maintain proper O2/C and H2O/C ratios to avoid hot spots and coking. Fuel must be completely evaporated before entering the reaction zone in order to prevent catalyst damage by coking. Computational fluid dynamics (CFD) is used to optimise the mixing process. Turbulent mixing, diesel spray injections and evaporation and simplified chemical reactions have been calculated. This revealed critical parts of the existing construction. However, experimental verification is necessary. To identify thermodynamic conditions for a possible carbon formation process, experiments with idealised model fuels as well as with real diesel fuel were carried out. Flow visualisation experiments serve for the verification of the CFD simulations. Quartz glass reactors as models of the reformers were operated under real mixing temperatures (400 °C) to observe the effect of the flow profile on fuel sprays. Experiments with coloured fuels were used to visualise the flow and concentration profiles in the mixing chamber. Results were compared with CFD models. Two patented reformers were designed as a result of the CFD optimisation. These were operated for 500 h and 1,000 h respectively with a commercially available diesel, showing very promising results.

Background: Exacerbation history (EH) is an important stratifying variable in the GOLD classification but its relationship to mortality is less clear. We used pooled data from the large TIOtropium Safety and Performance In Respimat ® (TIOSPIR™) trial, which found no difference between delivery systems of tiotropium on mortality, to investigate this issue. Aim: To determine whether EH (≥1 exacerbation in the past year), and inhaled corticosteroid (ICS) use at baseline affected outcomes of patients with COPD. Methods: This post-hoc analysis compared all-cause mortality and exacerbations between four patient subgroups characterized by ICS use at baseline and EH, adjusting for postbronchodilator FEV 1 , smoking status and concomitant long-acting β 2 -agonist (LABA) use at baseline. Results: Baseline characteristics such as age, body mass index, sex, race, smoking history, and history of cardiac disease were comparable between subgroups. Patients with EH had a higher risk of death (time to fatal event) compared to patients without EH. Comparable increases were seen in the subgroups with ICS use (hazard ratio [HR]: 1.31) and without ICS (HR: 1.26). Exacerbation risk (time to first exacerbation) was also increased in patients with EH (with and without ICS use) (Table). Conclusions: In patients with COPD from TIOSPIR™, EH increased the risk of death (time to fatal adverse event) and the risk of exacerbations irrespective of ICS use.