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Few clinical datasets exist in dentistry to conduct secondary research. Hence, a novel dental data repository called BigMouth was developed, which has grown to include 11 academic institutions contributing Electronic Health Record data on over 4.5 million patients. The primary purpose for BigMouth is to serve as a high-quality resource for rapidly conducting oral health-related research. BigMouth allows for assessing the oral health status of a diverse US patient population; provides rationale and evidence for new oral health care delivery modes; and embraces the specific oral health research education mission. A data governance framework that encouraged data sharing while controlling contributed data was initially developed. This transformed over time into a mature framework, including a fee schedule for data requests and allowing access to researchers from noncontributing institutions. Adoption of BigMouth helps to foster new collaborations between clinical, epidemiological, statistical, and informatics experts and provides an additional venue for professional development.

Severe Acute Respiratory Syndrome Coronavirus‐2 (SARS‐CoV‐2) is a pathogenic coronavirus causing COVID‐19 infection. The interaction between the SARS‐CoV‐2 spike protein and the human receptor angiotensin‐converting enzyme 2, both of which contain several cysteine residues, is impacted by the disulfide‐thiol balance in the host cell. The host cell redox status is affected by oxidative stress due to the imbalance between the reactive oxygen/nitrogen species and antioxidants. Recent studies have shown that Vitamin D supplementation could reduce oxidative stress. It has also been proposed that vitamin D at physiological concentration has preventive effects on many viral infections, including COVID‐19. However, the molecular‐level picture of the interplay of vitamin D deficiency, oxidative stress, and the severity of COVID‐19 has remained unclear. Herein, we present a thorough review focusing on the possible molecular mechanism by which vitamin D could alter host cell redox status and block viral entry, thereby preventing COVID‐19 infection or reducing the severity of the disease.

A workshop “Electronic Health Records and Pulmonary Function Data: Developing an Interoperability Roadmap” was held at the American Thoracic Society 2019 International Conference. “Interoperability” is defined as is the ability of different information-technology systems and software applications to directly communicate, exchange data, and use the information that has been exchanged. At present, pulmonary function test (PFT) equipment is not required to be interoperable with other clinical data systems, including electronic health records (EHRs). For this workshop, we assembled a diverse group of experts and stakeholders, including representatives from patient-advocacy groups, adult and pediatric general and pulmonary medicine, informatics, government and healthcare organizations, pulmonary function laboratories, and EHR and PFT equipment and software companies. The participants were tasked with two overarching Aobjectives: 1) identifying the key obstacles to achieving interoperability of PFT systems and the EHR and 2) recommending solutions to the identified obstacles. Successful interoperability of PFT data with the EHR impacts the full scope of individual patient health and clinical care, population health, and research. The existing EHR–PFT device platforms lack sufficient data standardization to promote interoperability. Cost is a major obstacle to PFT–EHR interoperability, and incentives are insufficient to justify the needed investment. The current vendor–EHR system lacks sufficient flexibility, thereby impeding interoperability. To advance the goal of achieving interoperability, next steps include identifying and standardizing priority PFT data elements. To increase the motivation of stakeholders to invest in this effort, it is necessary to demonstrate the benefits of PFT interoperability across patient care and population health.

An essential component of innovation for medical devices is a comprehensive market sizing assessment. This evaluation is useful for creating a solid business case and understanding market potential. This project involves the development of an online medical information dashboard for rapid market sizing assessments using business intelligence tools. A Spotfire front end was paired with a robust SQL database with market information. A visually appealing, simple, and clickable user interface was developed. This tool is designed with the technologist in mind and has value in the early prototyping stages of innovative new medical therapies.

Background Antibody based cancer therapies have achieved convincing success rates combining enhanced tumor specificity and reduced side effects in patients. Trastuzumab that targets the human epidermal growth factor related receptor 2 (HER2) is one of the greatest success stories in this field. For decades, trastuzumab based treatment regimens are significantly improving the prognosis of HER2-positive breast cancer patients both in the metastatic and the (neo-) adjuvant setting. Nevertheless, ≥ 50% of trastuzumab treated patients experience de-novo or acquired resistance. Therefore, an enhanced anti-HER2 targeting with improved treatment efficiency is still aspired. Methods Here, we determined cellular and molecular mechanisms involved in the treatment of HER2-positive BC cells with a new rabbit derived HER2 specific chimeric monoclonal antibody called “B100″. We evaluated the B100 treatment efficiency of HER2-positive BC cells with different sensitivity to trastuzumab both in vitro and in the presence of a human immune system in humanized tumor mice. Results B100 not only efficiently blocks cell proliferation but more importantly induces apoptotic tumor cell death. Detailed in vitro analyses of B100 in comparison to trastuzumab (and pertuzumab) revealed equivalent HER2 internalization and recycling capacity, similar Fc receptor signaling, but different HER2 epitope recognition with high binding and treatment efficiency. In trastuzumab resistant SK-BR-3 based humanized tumor mice the B100 treatment eliminated the primary tumor but even more importantly eradicated metastasized tumor cells in lung, liver, brain, and bone marrow. Conclusion Overall, B100 demonstrated an enhanced anti-tumor activity both in vitro and in an enhanced preclinical HTM in vivo model compared to trastuzumab or pertuzumab. Thus, the use of B100 is a promising option to complement and to enhance established treatment regimens for HER2-positive (breast) cancer and to overcome trastuzumab resistance. Extended preclinical analyses using appropriate models and clinical investigations are warranted.

RAL Space has delivered four engineering qualification model (EQM) front-end receivers (FERXs) for the Microwave Sounder (MWS) and Microwave Imager (MWI) on-board the MetOp Second Generation (MetOp-SG) satellites. This mission will provide the European and wider global communities with weather forecasting services from 2022 to 2043. The two EQM FERXs developed by RAL for the MWS operate in the 183 and 229 GHz frequency ranges, featuring average double sideband (DSB) noise figures (NFs) of 5.3 and 6.2 dB, respectively. This paper presents the design and main characterisation results of these two state-of-the-art FERXs for the MWS and compares their performance with other in-orbit microwave sounding instruments, including those on-board MetOp.

Rutherford Appleton Laboratory Space Department (RAL Space) and Radiometer Physics GmbH are responsible for the provision of millimetre-wave front-end receivers operating from 165 GHz to 664 GHz for three instruments on board the MetOp Second Generation (MetOp-SG) satellites. Qualification of the Engineering Qualification Models (EQMs) is recently completed. This paper presents the results of the EQM qualification for receivers operating at 165 GHz, 183 GHz and 229 GHz for the MWS and MWI instruments.

CD81 is a required receptor for hepatitis C virus (HCV) infection of human hepatocytes in vitro. We generated several high-affinity anti-human CD81 monoclonal antibodies (mAbs) that demonstrated potent, specific, and cross-genotype inhibition of HCV entry. One of these mAbs, K04, was administered to human liver chimeric mice before or after HCV infection to determine its ability to prevent HCV infection or spread of HCV infection, respectively. All vehicle control mice established HCV infection, reaching steady-state levels of serum HCV RNA by day 21. Pretreatment of mice with K04 prevented HCV infection in all mice (n = 5). Treatment of mice with mAb K04 every 3 days for 21 days, starting at 6 hours postinfection, resulted in effective inhibition of virus spread. In 3 mice that were sacrificed on day 24, serum HCV levels remained detectable, below the limit of quantification (LOQ), indicating that infection was established, but virus spread was blocked, by the anti-CD81 mAb. In 5 additional mice that were followed for a longer time, virus remained detectable, below LOQ, until days 24 and 30 in 4 of 5 mice. In the fifth mouse, viral load was quantifiable, but reduced to 64-fold below the mean viral load in vehicle control at day 24. In addition, 2 of 5 mice cleared the infection by day 30 and 1 mouse had undetectable virus load from day 6 onward. Conclusion: These results demonstrate that CD81 is required for HCV infection and virus spread in vivo, and that anti-CD81 antibodies such as K04 may have potential as broad-spectrum antiviral agents for prevention and treatment of HCV infection. (Hepatology 2015;61:1136–1144)

CD81 is an essential receptor for hepatitis C virus (HCV). K21 is a novel high affinity anti-CD81 antibody with potent broad spectrum anti-HCV activity in vitro. The pharmacokinetics (PK), pharmacodynamics and liver distribution of K21 were characterized in cynomolgus monkeys after intravenous (i.v.) administration of K21. Characteristic target-mediated drug disposition (TMDD) was shown based on the PK profile of K21 and a semi-mechanistic TMDD model was used to analyze the data. From the TMDD model, the estimated size of the total target pool at baseline (V(c) • R(base)) is 16 nmol/kg and the estimated apparent Michaelis-Menten constant (KM) is 4.01 nM. A simulation using estimated TMDD parameters indicated that the number of free receptors remains below 1% for at least 3 h after an i.v. bolus of 7 mg/kg. Experimentally, the availability of free CD81 on peripheral lymphocytes was measured by immunostaining with anti-CD81 antibody JS81. After K21 administration, a dose- and time-dependent reduction in free CD81 on peripheral lymphocytes was observed. Fewer than 3% of B cells could bind JS81 3 h after a 7 mg/kg dose. High concentrations of K21 were found in liver homogenates, and the liver/serum ratio of K21 increased time-dependently and reached ~160 at 168 h post-administration. The presence of K21 bound to hepatocytes was confirmed by immunohistochemistry. The fast serum clearance of K21 and accumulation in the liver are consistent with TMDD. The TMDD-driven liver accumulation of the anti-CD81 antibody K21 supports the further investigation of K21 as a therapeutic inhibitor of HCV entry.

Sweet sorghum (Sorghum bicolor [L.] Moench) accumulates fermentable sugars in the stem and is increasingly being studied as a potential source of feedstock for bioethanol production. The objective of this study was to evaluate biomass and grain yield in five sweet sorghum cultivars (Dale, M81E, Sugar Drip, Della and Keller) and to determine quality of extractable juice and grain. Randomized complete block experiments were performed in the summer of 2009, 2010, and 2011. Leaf dry weight varied with year and cultivar and averaged 6177 kg·ha-1. Fresh stem weight ranged from 21 to 54 Mg·ha-1 with a mean across years and cultivars of 32.9 Mg·ha-1. Variations in stem weight were correlated with extractable juice volumes that ranged from 10 to 24 m3·ha-1. Juice Brix values fell within a narrow range (14% - 19%) across years and cultivars with an average of 15.6%. In all production years, theoretical sugar and ethanol yield were always numerically higher for Keller and M81E. Grain yield was lowest in Keller (90 kg·ha-1), but ranged from 400 to 1300 kg·ha-1 in other cultivars with a mean of 584 kg·ha-1 across years. However, Keller had the highest starch content with a lower proportion of resistant starch in the grain. Except for Keller, the cultivars tested are potential sources of both fermentable sugars and grain.

Stinging nettle (Urtica dioica) is a specialty crop with economic potential. Apart from being harvested and consumed as a leafy vegetable, stinging nettle has well-documented applications in alternative medicine and industry. However, research on stinging nettle mineral nutrition is insufficient and the current study is part of efforts to establish agronomic guidelines for managed cultivation. Greenhouse experiments were conducted over two seasons (summer and fall) to evaluate stinging nettle growth and dry matter partitioning in response to variations in the supply of nitrogen (N), and N in combination with potassium (K). In the first experiment, seedlings were transplanted into potted media amended with N applied at rates equivalent to 0, 15, 30, 45, 60, and 75 g·m−2, while Expt. 2 consisted of N (15, 45, and 75 g·m−2 equivalent) and K (4, 8, and 12 g·m−2 equivalent) applied in factorial combinations. In Expt. 1, stinging nettle growth was positively correlated with N supply up to 60 g·m−2 during the reproductive phase (summer) and 75 g·m−2 during the vegetative phase (fall), while there was a slight decline in growth and dry matter yield at the highest level of K (12 g·m−2) at all N levels in Expt. 2. In both experiments, growth and dry matter accumulation was higher in the fall than in summer, and high N accounted for significantly more vegetative growth with a concomitant increase in aboveground biomass. Our results suggest that K should be applied at a rate below the growth-limiting threshold of 12 g·m−2. In this study, N strongly stimulated aboveground growth suggesting it is the most important element in stinging nettle nutrition.

The demographic change causes an imbalance between the number of elderly in need of support and the number of caring staff. Therefore, it is important to help older adults keep their independence. Forgetting is a common obstacle people have to face when they become older which can be moderated by social robots by reminding on tasks. Since most elderly people are not used to robots a challenge in HRI is to identify aspects of a robot’s design to promote its acceptance. We present two different personas (companion vs. assistant) for a robotic platform by manipulating verbal and nonverbal behavior. A study was conducted in assisted living accommodations with the robot reminding on appointments to review if the persona influences the robot’s acceptance. Results indicate that the companion version of the robot was better accepted and perceived more likeable and intelligent compared to the assistant version.

In this study, we describe novel tetravalent, bispecific antibody derivatives that bind two different epitopes on the HIV coreceptor CCR5. The basic protein formats that we applied were derived from Morrison-type bispecific antibodies: whole IgGs to which we connected single-chain antibodies (scFvs) via (Gly 4 Ser) n sequences at either the C or N terminus of the light chain or heavy chain. By design optimization, including disulfide stabilization of scFvs or introduction of 30-amino-acid linkers, stable molecules could be obtained in amounts that were within the same range as or no less than 4-fold lower than those observed with monoclonal antibodies in transient expression assays. In contrast to monospecific CCR5 antibodies, bispecific antibody derivatives block two alternative docking sites of CCR5-tropic HIV strains on the CCR5 coreceptor. Consequently, these molecules showed 18- to 57-fold increased antiviral activities compared to the parent antibodies. Most importantly, one prototypic tetravalent CCR5 antibody had antiviral activity against virus strains resistant to the single parental antibodies. In summary, physical linkage of two CCR5 antibodies targeting different epitopes on the HIV coreceptor CCR5 resulted in tetravalent, bispecific antibodies with enhanced antiviral potency against wild-type and CCR5 antibody-resistant HIV-1 strains.

In recent years, a physical phenomenon referred to as Negative Group Delay (NGD) or superluminal wave propagation has been implemented in electronic circuitry and shown to temporally advance the detection of analog signals. Specifically, the output of such a circuit precedes the complete detection of its input as the group (and therefore time) delay through the circuit is negative. In this article we describe the background and theory behind this phenomenon, discuss its implementation in electronics and demonstrate a specific biomedical signal application (the human ECG). We discuss some key NGD circuit design considerations/configurations and potential applications in which this technology could offset or eliminate entirely, closed-loop control system delays.

To identify monoclonal antibodies (mAbs) with high potency and novel recognition sites, more than 25,000 of mouse hybridomas were screened and 4 novel anti-human CCR5 mAbs ROAb12, ROAb13, ROAb14, and ROAb18 showing potent activity in cell-cell fusion (CCF) assay were identified. These mAbs demonstrated potent antiviral activities in both single-cycle HIV infection (IC(50) range: 0.16-4.3 microg/ml) and PBMC viral replication (IC(50) range: 0.02-0.04 microg/ml) assays. These potent antiviral effects were donor-independent. All 4 mAbs were also highly potent in the PhenoSense assay against 29 HIV isolates covering clade A through G. In all antiviral assays, these mAbs showed potency superior to the previously reported mAb 2D7 in side-by-side comparison studies. All 4 mAbs were also fully active against viruses resistant to HIV fusion inhibitor enfuvirtide and CCR5 antagonist maraviroc. Although ROAb12, ROAb14, and ROAb18 inhibited RANTES, MIP1alpha and MIP1beta binding and cell activation, the other novel mAb ROAb13 was inactive in inhibiting cell activation by these three ligands. Furthermore, highly synergistic antiviral effects were found between mAb ROAb13 and 2D7 or ROAb12. In addition, none of these mAbs showed agonist activity or caused internalization of the CCR5 receptor.

Six mouse anti-human CCR5 monoclonal antibodies (mAbs) that showed potent antiviral activities were identified from over 26,000 mouse hybridomas. The epitopes for these mAbs were determined by using various CCR5 mutants, including CCR5/CCR2B chimeras. One mAb, ROAb13, was found to bind to a linear epitope in the N terminus of CCR5. Strikingly, the other five mAbs bind to epitopes derived from extracellular loop 2 (ECL2). The three most potent mAbs, ROAb12, ROAb14, and ROAb18, require residues from both the N-terminal (Lys171 and Glu172) and C-terminal (Trp190) halves of ECL2 for binding; two other mAbs, ROAb10 and ROAb51, which also showed potent antiviral activities, require Lys171 and Glu172 but not Trp190 for binding. Binding of the control mAb 2D7 completely relies on Lys171 and Glu172. Unlike 2D7, the novel mAbs ROAb12, ROAb14, and ROAb18 do not bind to the linear peptide 2D7-2SK. In addition, all three mAbs bind to monkey CCR5 (with Arg at position 171 instead of Lys); however, 2D7 does not. Since five of the six most potent CCR5 mAbs derived from the same pool of immunized mice require ECL2 as epitopes, we hypothesize that CCR5 ECL2 contains the dominant epitopes for mAbs with potent antiviral activities. These dominant epitopes were found in CCR5 from multiple species and were detected in large proportions of the total cell surface CCR5. mAbs recognizing these epitopes also showed high binding affinity. A homology model of CCR5 was generated to aid in the interpretation of these dominant epitopes in ECL2.

The application of straw mulch to organic seed potatoes ( Solanum tuberosum L.) has been shown to reduce virus incidence. In order to determine the associated agronomic effects of straw mulch, applied at 2.5–5 t ha −1 , on soil nitrate dynamics, weed development, tuber yield and soil erosion, 12 field experiments were evaluated. Experiments were conducted on organic farms over 3 years at two locations in a temperate climate (635–709 mm precipitation/year; 8.1 °C mean air temperature) on loamy silt soils. Tuber yield and tuber size distribution were not influenced significantly by mulching. However, the risk of undesirable post harvest N-leaching was significantly reduced due to the immobilization of nitrate–N after harvest at 6.8–7.0 kg N t −1 straw in two experiments (18–34 kg NO 3 –N ha −1 ). There was no consistent effect of straw mulch on number of weeds, weed cover and above ground biomass of weeds. The fact that yield and weed development were not significantly affected by straw mulch is mainly attributed to the relatively low amounts of straw applied. Soil erosion was reduced by >97% in a rain simulation experiment on a potato field of 8% slope with 20% crop cover. Soil loss was greatest (1606 g m −2 ) in the unmulched treatment, and 31, 42 and 26 g m −2 in treatments with chopped straw at 1.25, 2.5 and 5 t ha −1 , respectively.

The activity and biomass of soil microorganisms were determined in samples at 0—140 cm depth taken from an arable site, where the soil has been developed by erosion and colluvial deposition overlaying a black earth at 70—110 cm depth. The central aim was to get an insight into the breakdown of increasingly old and thus recalcitrant soil organic matter down the profile, effects on the availability of C to microorganisms and the microbial community structure. From 0 to 140 cm depth, microbial biomass C decreased by 96%, biomass N by 97%, the adenylates ATP, ADP, and AMP as well as the basal respiration rate by 89%. No ergosterol was measured at 120—140 cm depth. All soil biological properties decreased in distinct steps after 30 cm and 50 cm depth. At 30—90 cm depth, the amounts of soil organic C and microbial biomass C per hectare of the present colluvium exceeded nearly three-fold those in undisturbed aeolian loess sediments. The cation exchange significantly affected the relationships between microbial biomass C, biomass N, and the adenylates. As a consequence, none of the ratios between the soil microbial biomass properties revealed constant gradients throughout the profile. The adenylate energy charge (AEC) varied between the different soil layers insignificantly around a mean of 0.71. It was the most stable ratio down the profile showing absolutely no depth gradient, the lowest depth-to-depth variation, and also the lowest within depth variability. The other ratios between soil organic C, basal respiration, ergosterol, microbial biomass C and biomass N also did not reveal any marked changes in the microbial community structure. Mikrobielle Bodeneigenschaften eines Tschernosems unter Kolluvium Aktivitat und Biomasse von Bodenmikroorganismen wurden in Proben aus einer Tiefe von 0—140 cm untersucht, die von einer Ackerflache genommen wurden, auf der sich der Boden durch Kolluviation uber einer Schwarzerde in 70—110 cm Tiefe entwickelt hat. Das zentrale Ziel war es, einen Einblick in den Abbau von mit der Tiefe eines Profils zunehmend alter und deshalb schwer zersetzbarer organischer Bodensubstanz und die Auswirkungen auf die Verfugbarkeit von C fur Mikroorganismen und die Struktur der mikrobiellen Gemeinschaften zu untersuchen. Von 0 bis 140 cm Tiefe nahm C in mikrobieller Biomasse um 96% ab, N in mikrobieller Biomasse um 97%, die Adenylate ATP, ADP und AMP sowie die Basalatmung um 89 %. Ergosterol konnte in einer Tiefe von 120—140 cm nicht gemessen werden. Diskrete Stufen in der Abnahme traten nach 30 cm und 50 cm Tiefe fur alle bodenbiologischen Eigenschaften auf. In 30—90 cm Tiefe des Kolluviums ubertraf die Menge an C in organischer Bodensubstanz und C mikrobieller Biomasse pro Hektar diejenige in Boden aus ungestorten Lossen um nahezu das Dreifache. Die Kationen-Austausch-Kapazitat hatte einen signifikanten Einfluss auf die Beziehungen zwischen C und N in mikrobieller Biomasse und den Adenylaten. Das hat zur Konsequenz, dass keiner der Quotienten zwischen mikrobiellen Bodeneigenschaften konstante Gradienten im Profil aufwies. Der Adenylate-Energy-Charge (AEC) variierte zwischen den verschiedenen Tiefenstufen ohne Signifikanz um einen Mittelwert von 0.71. Im Profil abwarts war er damit der stabilste Quotient, ohne jeden Tiefengradienten, mit der geringsten Variation von Tiefen- zu Tiefenstufe, und ebenfalls der geringsten Variabilitat innerhalb einer Tiefenstufe. Auch die ubrigen Quotienten zwischen C in organischer Bodensubstanz, Basalatmung, Ergosterol, C und N in mikrobieller Biomasse zeigten keine deutlichen Veranderungen in der Struktur der mikrobiellen Gemeinschaften.

There is an increasing need for in vitro testing of compounds for topical application. Reconstructed epidermal models may provide a suitable and relevant model for screening compounds that may affect the activities of phase I and II enzymes involved in epidermal detoxification. In this study, we measured the activity of a phase I enzyme, cytochrome P450 IA1, i.e. 7-ethoxyresorufin-O-deethylase (EROD) and 7-ethoxycoumarin-O-deethylase (ECOD) activities, and that of a phase II enzyme, glutathione S-transferase (GST). The enzyme activities were determined in cultured keratinocytes, reconstructed epidermal models and samples of human epidermis or hair follicle. EROD activity was detected in cultured keratinocytes and was induced by 3-methylcholanthrene (3-MC) and β-naphthoflavone. The level of induction increased with increasing confluence. Induced EROD activity could be inhibited by clotrimazole in a dose-dependent manner. However, EROD activity was not detected in either hair follicles or untreated epidermal models but could be induced by 3-MC. The ability to induce EROD activity in epidermal models was batch dependent, and clotrimazole was able to inhibit the induced EROD activity. ECOD activity was detected in untreated models and paralleled EROD activity. GST activity was detected in cultured keratinocytes and all epidermal models. GST activity in models was equal or higher than the activity in epidermal samples. Reconstructed skin models may be useful to study the effects of non-water-soluble topical formulations on xenobiotic metabolism.

OBJECTIVES In order to evaluate the benefit provided through less invasive surgical techniques for the treatment of multivessel coronary artery disease, a prospective clinical trial was started. METHODS Group 1 included 53 patients (38 males, 15 females, age 51-79 years, mean 62.8 +/- 6.1 years) receiving conventional bypass surgery, group 2 included 69 patients (59 male, 10 female, age 43-82 years, mean 61.9 +/- 8.6 years) receiving less invasive surgical procedure including minithoracotomy in combination with cardiopulmonary bypass. RESULTS No perioperative death occurred in the whole series of patients. Time of operation was 267 +/- 61 min in group 2 and 162.9 +/- 53.6 min in group 1. Intensive Care Unit stay was 1 day for both groups and Hospitalization 6.9 +/- 6.0 for group 1 and 7.5 +/- 2.6 days for group 2. Perioperative bleeding was less in group 2 (P > 0.01). Back and chest pain assessment on postoperative day 3 showed less pain in group 2 (P < 0.05). Three-month follow-up revealed ischemia in stress electrocardiogram in two patients (3.8%) in group 1 and in 2 patients (2.9%) in group 2. Coronary angiograms confirmed the stress ECG findings. There was one (1.4%) redo operation in group 2 and two (3.8%) in group 1. CONCLUSIONS Both techniques are equal efficient. Even though time of operation is longer in patients receiving less invasive procedure, intensive care unit stay and hospitalization is exactly as long. Patients receiving minimally invasive surgery bleed less and have less pain early postoperatively.

Background . In a prospective clinical trial, a group of patients receiving less invasive surgical procedure, including minithoracotomy in combination with cardiopulmonary bypass (group 1), was compared to a group of patients receiving conventional bypass surgery (group 2) for the treatment of coronary artery disease. Methods . Group 1 included 85 patients (71 men, 14 women, aged 39 to 82 years, median 61.1 ± 9.0 years); group 2 included 53 patients (38 men, 15 women, aged 51 to 79 years, median 62.0 ± 6.1 years). Results . There were no perioperative deaths in the whole series of patients. Time of operation was 256 ± 43 minutes in group 1 and 150.0 ± 53.6 minutes in group 2. Hospitalization was 6.0 ± 1.4 days and intensive care unit stay 1 day for both groups. Back pain assessment on postoperative day 3 showed less pain in group 1. Three-month follow-up revealed ischemia in stress electrocardiogram in 2 patients (2.5%) in group 1 and in 2 patients (4.1%) in group 2. Coronary angiograms confirmed the stress-electrocardiogram findings. Conclusions . Surgical results are equal for both techniques. Even though time of operation is longer in patients receiving less invasive procedures, intensive care unit stay and hospital stays are the same length. Early postoperative back pain is less in group 1 and combined with faster convalescence.

Objective: The treatment of coronary single vessel disease under minimally invasive surgical conditions was followed by the treatment of coronary multivessel disease using a new technique. Methods: Using this technique 100 patients (80 male, 20 female, median age 61.0 ± 8.9 years, ranged from 39 to 82 years) with coronary single vessel disease, double vessel disease or multivessel disease were treated between November 1996 and December 1997. Via a small (6-9 cm) left lateral chest incision in the second or third intercostal space, the left internal thoracic mammary artery (LIMA) was harvested and access to the central portion of the heart including the ascending aorta was obtained. In parallel, saphenous vein segments were harvested. Arterial cannulation was instituted via the ascending aorta, thus avoiding retrograde flow. In all patients except three the LIMA was used for the left anterior descending artery (LAD). In addition vein grafts were used for revascularization of the other coronary arteries. All cardiac anastomoses were performed during cardioplegic arrest after external aortic cross clamping and antegrade application of cardioplegia. Results: No death or intraoperative complications were observed in this series. The median hospital stay was 6.0 ± 1.4 days (median ± SEM). Postoperative complications were reexplored for bleeding (n = 1), delayed wound healing (n = 2), wound infections (n = 4), lymphatic fistulas (n = 4), and a chest wall hernia (n = 1). Conclusions: This minimally invasive surgical technique presents a safe alternative to conventional coronary artery surgery avoiding sternotomy related complications and decreasing hospital stay and morbidity.

We present new sound and complete axiomatizations of type equality and subtype inequality for a first-order type language with regular recursive types. The rules are motivated by coinductive characterizations of type containment and type equality via simulation and bisimulation, respectively. The main novelty of the axiomatization is the fixpoint rule (or coinduction principle). It states that from A,P $$\vdash$$ P one may deduce A $$\vdash$$ P, where P is either a type equality τ = τ' or type containment τ ≤ τ' and the proof of the premise must be contractive in a sense we define in this paper. In particular, a proof of A, P $$\vdash$$ P using the assumption axiom is not contractive. The fixpoint rule embodies a finitary coinduction principle and thus allows us to capture a coinductive relation in the fundamentally inductive framework of inference systems. The new axiomatizations are more concise than previous axiomatizations, particularly so for type containment since no separate axiomatization of type equality is required, as in Amadio and Cardelli's axiomatization. They give rise to a natural operational interpretation of proofs as coercions. In particular, the fixpoint rule corresponds to definition by recursion. Finally, the axiomatization is closely related to (known) efficient algorithms for deciding type equality and type containment. These can be modified to not only decide type equality and type containment, but also construct proofs in our axiomatizations efficiently. In connection with the operational interpretation of proofs as coercions this gives efficient (O(n 2) time) algorithms for constructing efficient coercions from a type to any of its supertypes or isomorphic types. More generally, we show how adding the fixpoint rule makes it possible to characterize inductively a set that is coinductively defined as the kernel (greatest fixed point) of an inference system.

Stinging nettle (Urtica dioica L.) has a long history of usage and is currently receiving attention as a source of fiber and alternative medicine. In many cultures, nettle is also eaten as a leafy vegetable. In this study, we focused on nettle yield (edible portion) and processing effects on nutritive and dietary properties. Actively growing shoots were harvested from field plots and leaves separated from stems. Leaf portions (200 g) were washed and processed by blanching (1 min at 96–98°C) or cooking (7 min at 98-99°C) with or without salt (5 g·). Samples were cooled immediately after cooking and kept in frozen storage before analysis. Proximate composition, mineral, amino acid, and vitamin contents were determined, and nutritive value was estimated based on 100 g serving portions in a 2000 calorie diet. Results show that processed nettle can supply 90%–100% of vitamin A (including vitamin A as β-carotene) and is a good source of dietary calcium, iron, and protein. We recommend fresh or processed nettle as a high-protein, low-calorie source of essential nutrients, minerals, and vitamins particularly in vegetarian, diabetic, or other specialized diets. Published version

The development of heterodyne receiver channels at frequencies ranging from 183 GHz up to 664 GHz, and compatible with the requirements of both the ICI instrument onboard MetOp-SG and the ISMAR instrument onboard the FAAM aircraft are presented. In order to optimize the performance VS cost factor, multi-channels architecture that enhances commonalities as well as maximum redundancies in the use of planar Schottky diode is adopted. The performance of each component is close if not at the state-of-the-art. For these receivers, broadband high power and high efficiency mutlipliers, and also high sensitivity subharmonic mixers are required. These developments are also possible thanks to the availability of novel test equipment systems such as VNA and Spectrum Analyser extenders up to 750 GHz in order to characterize fully each component. Performance of these submillimetre wave test equipment systems developed by RPG is also presented.

In the framework of the Phase A study for MetOp Second Generation mission (MetOp-SG), CORISTA developed an instrument performance model for MicroWave Imager (MWI) instrument that is currently studied for MetOp-SG. MWI is a conically scanning microwave radiometer, consisting of 28 channels and covering frequency range from 18 GHz up to 183 GHz. The corresponding algorithms have been implemented by means of dedicated software aimed to analyze the performance of the MWI. An analysis tool was developed for the instrument channels as well as for the overall system performance parameters. The software tool was developed in MatLab language.

The autoimmune phenomena associated with destruction of the beta cell in pancreatic islets and development of type 1 (insulin-dependent) diabetes mellitus (IDDM) include circulating islet cell antibodies. We have immortalized peripheral blood lymphocytes from prediabetic individuals and patients with newly diagnosed IDDM by Epstein-Barr virus transformation. IgG-positive cells were selected by anti-human IgG-coupled magnetic beads and expanded in cell culture. Supernatants were screened for cytoplasmic islet cell antibodies using the conventional indirect immunofluorescence test on cryostat sections of human pancreas. Six islet cell-specific B-cell lines, originating from a patient with newly diagnosed IDDM, could be stabilized on a monoclonal level. All six monoclonal islet cell antibodies (MICA 1-6) were of the IgG class. None of the MICA reacted with human thyroid, adrenal gland, anterior pituitary, liver, lung, stomach, and intestine tissues but all six reacted with pancreatic islets of different mammalian species and, in addition, with neurons of rat cerebellar cortex. MICA 1-6 were shown to recognize four distinct antigenic epitopes in islets. Islet cell antibody-positive diabetic sera but not normal human sera blocked the binding of the monoclonal antibodies to their target epitopes. Immunoprecipitation of 35S-labeled human islet cell extracts revealed that a protein of identical size to the enzyme glutamate decarboxylase (EC 4.1.1.15) was a target of all MICA. Furthermore, antigen immunotrapped by the MICA from brain homogenates showed glutamate decarboxylase enzyme activity. MICA 1-6 therefore reveal glutamate decarboxylase as the predominant target antigen of cytoplasmic islet cell autoantibodies in a patient with newly diagnosed IDDM.

In passaging experiments, we isolated HIV strains resistant to MAb3952, a chemokine (C-C motif) receptor 5 (CCR5) monoclonal antibody (MAb) that binds to the second extracellular domain (extracellular loop 2 [ECL-2]) of CCR5. MAb3952-resistant viruses remain CCR5-tropic and are cross-resistant to a second ECL-2-specific antibody. Surprisingly, MAb3952-resistant viruses were more susceptible to RoAb13, a CCR5 antibody binding to the N terminus of CCR5. Using CCR5 receptor mutants, we show that MAb3952-resistant virus strains preferentially use the N terminus of CCR5, while the wild-type viruses preferentially use ECL-2. We propose this switch in the CCR5 binding site as a novel mechanism of HIV resistance.

Clinical scar assessment lacks standardized methodology and consensus on the most appropriate evaluation instrument. This study empirically evaluated whether area scars could be validly assessed by naive observers with the objective to develop and validate a novel multidimensional visual analogue scale (VAS) for the assessment of area scars.Standardized digital photographs of radial forearm free flap (RFFF) donor sites were obtained. Naive observers evaluated the images in three sequential psychophysical experiments, which led to the development of the new scar scale. These experiments involved initial evaluation of four dimensions (pigmentation, vascularity, observer comfort, acceptability) using a paired comparison (PC) paradigm and correlation with ratings of overall severity using a VAS, and initial VAS test phase followed by formal debriefing, and, subsequently, evaluation of a VAS for the four dimensions in addition to contour. Validation involved determination of intra- and interrater reliability and correlational analysis.Across all three experiments, 56 observers evaluated 101 images, generating 12 720 observations for analysis. PC data demonstrated that observers could assess scars with high reliability and internal consistency for all dimensions (95%). Overall (VAS) severity correlated highly with all dimensions, including contour. The new VAS yielded high levels of correlation (r = .72-.98, p.01).Comprehensive VAS analysis demonstrates high reliability in mirroring PC results for multiple dimensions of area scars. These data support our novel multidimensional VAS method as a valid, reliable, simple, and time-efficient instrument for clinical and research use. We introduce the Western Scar Index as a new measurement tool with many potential applications.