Evolution of femtosecond laser damage in a hafnia-silica multi-layer dielectric coating.

To optimize optical coating materials, designs, and technologies for high damage resistance, understanding the growth of laser damage is of paramount importance. In this Letter, we show the evolution of femtosecond laser damage in a hafnia-silica (HfO2/SiO2) multilayer dielectric mirror coating. Depending on various spatial features of damaged sites, we identified several regimes of the laser-material interaction with varying laser fluence and incident number of pulses. A change in surface roughness has been observed only for a small number of pulses, and interestingly, a threshold number of pulses is found for nanocrack formation. We report the polarization-dependent orientation of nanocracks and their growth with an increasing number of pulses. The presented results demonstrate that the laser damage originates from the nanobumps and surface roughening, which then leads to the formation of nanocracks. The presented experimental results acknowledge the existing theoretical models in bulk dielectrics to explain the formation of nanostructures by interference of the incident laser with the scattering radiation from laser-induced inhomogeneities and growth of the field enhancement due to nanoplasma.

Reduced fetal growth velocities and the association with neonatal outcomes in appropriate-for-gestational-age neonates: a retrospective cohort study.

BACKGROUND: Fetal growth restriction is, despite advances in neonatal care and uptake of antenatal ultrasound scanning, still a major cause of perinatal morbidity. Neonates with birth weight > 10th percentile are assumed to be appropriate-for-gestational-age (AGA), although many are at increased risk of perinatal morbidity, because of undetected mild restriction of growth potential. We hypothesized that within AGA neonates, reduced fetal growth velocities are associated with adverse neonatal outcome. METHODS: A retrospective cohort study of singleton pregnancies, in the Maastricht University Medical Centre (MUMC) between 2010 and 2016. Women had two fetal biometry scans (18-22 weeks and 30-34 weeks of gestational age) and delivered a newborn with a birth weight between the 10th-80th percentile. Differences in growth velocities of the abdominal circumference (AC), biparietal diameter (BPD), head circumference (HC) and femur length (FL) were compared between the suboptimal AGA (sAGA) (birth weight centiles 10-50) and optimal AGA (oAGA) (birth weight centiles 50-80) group. We assessed the association between velocities and neonatal outcomes. RESULTS: We included 934 singleton pregnancies. In the suboptimal AGA group, fetal growth velocities were lower (in mm/week): AC 10.72 ± 1.00 vs 11.23 ± 1.00 (p < .001), HC 10.50 ± 0.80 vs 10.68 ± 0.77 (p = 0.001), BPD 3.01 ± 0.28 vs 3.08 ± 0.27 (p < .0001) and FL 2.47 ± 0.21 vs 2.50 ± 0.22 (p = 0.014), compared to the optimal AGA group. Neonates with an adverse neonatal outcome had significantly lower growth velocities (in mm/week) of: AC 10.57 vs 10.94 (p = 0.034), HC 10.28 vs 10.59 (p = 0.003) and BPD 2.97 vs 3.04 (p = 0.043) compared to those with normal outcome. An inverse association was observed between the AC velocity and a composite adverse neonatal outcome (OR) = 0.667 (95%CI 0.507-0.879, p = 0.004), and between the AC velocity and neonates with NICU stay (OR) = 0.733 (95%CI 0.570-0.942, p = 0.015). Neonates with a birthweight lower than expected (based on the abdominal circumference at 20 weeks) had significantly more composite adverse neonatal outcomes 8.5% vs 5.0% (p = 0.047), NICU stays 9.6% vs 3.8% (p < .0001) and hospital stays 44.4% vs 35.6% (p = 0.006). CONCLUSIONS: Appropriate-for-gestational-age neonates are a heterogeneous group with some showing suboptimal fetal growth. Abnormal fetal growth velocities, especially abdominal circumference velocity, are associated with adverse neonatal outcome and can potentially improve the detection of mild growth restriction when used in multivariate models.

En Bloc Liver Kidney Transplantation Using Donor Splenic Artery as Inflow to the Kidney: Report of Two Cases.

The number of simultaneous liver-kidney transplants has been increasing. This surgery is associated with an increased risk of complications, longer duration of surgery and longer ischemia time for the renal allograft. Two patients listed for liver-kidney transplant at our center underwent en bloc combined liver-kidney transplantation using donor splenic artery as inflow. Patient 1 previously underwent cardiac catheterization that was complicated by a bleeding pseudoaneurysm of the right external iliac artery that required endovascular stenting of the external iliac artery and embolization of the inferior epigastric artery. Patient 2 was on vasopressor support and continuous renal replacement therapy at the time of transplant. In this paper, we described a novel technique of en bloc liver-kidney transplant with simultaneous reperfusion of both allografts using the donor splenic artery for renal inflow. This technique is useful for decreasing cold ischemia time and total operative time by simultaneous reperfusion of both allografts. It is a useful technical variant that can be used in patients with severe disease of the iliac arteries.

Standardizing terms, definitions and concepts for describing and interpreting unwanted immunogenicity of biopharmaceuticals: recommendations of the Innovative Medicines Initiative ABIRISK consortium.

Biopharmaceuticals (BPs) represent a rapidly growing class of approved and investigational drug therapies that is contributing significantly to advancing treatment in multiple disease areas, including inflammatory and autoimmune diseases, genetic deficiencies and cancer. Unfortunately, unwanted immunogenic responses to BPs, in particular those affecting clinical safety or efficacy, remain among the most common negative effects associated with this important class of drugs. To manage and reduce risk of unwanted immunogenicity, diverse communities of clinicians, pharmaceutical industry and academic scientists are involved in: interpretation and management of clinical and biological outcomes of BP immunogenicity, improvement of methods for describing, predicting and mitigating immunogenicity risk and elucidation of underlying causes. Collaboration and alignment of efforts across these communities is made difficult due to lack of agreement on concepts, practices and standardized terms and definitions related to immunogenicity. The Innovative Medicines Initiative (IMI; www.imi-europe.org), ABIRISK consortium [Anti-Biopharmaceutical (BP) Immunization Prediction and Clinical Relevance to Reduce the Risk; www.abirisk.eu] was formed by leading clinicians, academic scientists and EFPIA (European Federation of Pharmaceutical Industries and Associations) members to elucidate underlying causes, improve methods for immunogenicity prediction and mitigation and establish common definitions around terms and concepts related to immunogenicity. These efforts are expected to facilitate broader collaborations and lead to new guidelines for managing immunogenicity. To support alignment, an overview of concepts behind the set of key terms and definitions adopted to date by ABIRISK is provided herein along with a link to access and download the ABIRISK terms and definitions and provide comments (http://www.abirisk.eu/index_t_and_d.asp).

Social neighborhood environment and sports participation among Dutch adults: does sports location matter?

Studies on the relation between the social neighborhood environment and sports participation have produced inconsistent results. Use of generic sports outcomes may have obscured associations only apparent for sports at certain locations. This study aims to assess the association between the social neighborhood environment and three location-specific sports outcomes. Repeated cross-sectional data on sports participation (any type of sports, sports at indoor sports clubs, sports at outdoor sports clubs, sports on streets) were obtained from 20 600 adults using the Dutch national health survey 2006-2009. Data on neighborhood social safety and social capital were obtained using the Dutch Housing Research 2006. Over 40% of Dutch adults participated in any type of sports. Indoor sports clubs were most popular. Multilevel logistic regression analyses revealed that neighborhood social safety was positively associated with sports at indoor sports clubs [odds ratio (OR) = 1.25, 95% confidence interval (CI) = 1.06-1.48), but not with the other sports outcomes. Contrary, neighborhood social capital was positively associated with sports on streets only (OR = 1.69, 95% CI = 1.17-2.44). The results suggest that a positive social neighborhood environment enhances sports participation, but that this impact depends on the location of the sports activity. This study highlights the importance of using location-specific sports outcomes when assessing environmental determinants.

Laboratory diagnosis of paraneoplastic pemphigus.

BACKGROUND: Paraneoplastic pemphigus (PNP) is a multiorgan disease characterized by antibodies against plakins, desmogleins and the α2-macroglobulin-like-1 (A2ML1) protein, in association with an underlying neoplasm. Accurate diagnosis relies on the demonstration of these autoantibodies in serum. OBJECTIVES: To evaluate the value of different laboratory techniques in the serological diagnosis of PNP. METHODS: We performed immunoblotting, envoplakin (EP) enzyme-linked immunosorbent assay (ELISA), indirect immunofluorescence (IIF) on rat bladder, radioactive immunoprecipitation and a nonradioactive combined immunoprecipitation-immunoblot assay. Additional assays included BP180 ELISA and BP230 ELISA. We included the sera of 19 patients with PNP and 40 control subjects. RESULTS: The sensitivities were 63% for anti-EP ELISA, 74% for rat bladder IIF, 89% for immunoblotting, 95% for radioactive immunoprecipitation and 100% for nonradioactive immunoprecipitation. Specificities ranged from 86% to 100%. The BP180 and BP230 ELISAs had low sensitivity and specificity for PNP. The combination of rat bladder IIF and immunoblot showed 100% sensitivity and specificity. The analysis of sequential PNP sera showed that antibody titres may decrease over time, possibly resulting in negative outcomes for EP ELISA and rat bladder IIF studies. CONCLUSIONS: The detection of autoantibodies against EP and periplakin, or A2ML1 by immunoprecipitation is most sensitive for PNP. The combination of rat bladder IIF and immunoblotting is equally sensitive and highly specific, and represents an alternative valuable and relatively easy approach for the serological diagnosis of PNP.

[Normalisation of screening HASE for 4- to 4½-year-old children]. / Normierung des Screening HASE für 4- bis 4 ½-jährige Kinder.

For reasons of prevention medical examinations of school beginners are brought forward up to 2 years before school enrollment. In Baden-Württemberg HASE is used as screening for risks in the acquisition of language and in learning to read and write. Up to now norms were insufficient for the age-group of 4;0-4;5 years. Based on the results of 3 354 children the norms for this age-group could be recalculated and are now available as percentile ranks, T-scores, and C-scores.

[The new preschool examination in Baden-Wuerttemberg: what determinants influence the school medical evaluation special need for language promotion in childhood development?]. / Die neue Einschulungsuntersuchung in Baden-Württemberg: Welche Determinanten beeinflussen die schulärztliche Gesamtbewertung Intensiver pädagogischer Förderbedarf im kindlichen Entwicklungsfeld Sprache?

BACKGROUND AND AIMS: The new examination before primary school enrollment in Baden-Wuerttemberg aims at detecting problems in infant development with regard to later school success in time to initiate supporting measures, especially to improve the language skills of children with other native languages. By a 2-level process composed of a screening of language skills (HASE and KVS) and an additional test (SETK 3-5) of children who did not pass the screening, the school physicians attested special needs for language promotion in the kindergarten. This study looked for associated risks of children with special needs for language promotion. The degree of test quality of the 2-level process for identifying special needs for language promotion was determined. METHODS AND RESULTS: This cross-sectional analysis explored findings of n=80,781 children in the new examination before primary school enrollment of the data-set of Baden-Wuerttemberg (children with school enrollment 2011). 56,352 children (69.8%) were speaking German, 24,429 children (30.2%) had other family languages. 20,461 children (25.3%) had special needs for language promotion in the kindergarten. A logistic regression model to determine main risks of special needs for language promotion was developed. Main effects were other native languages (OR 5.1 [4.8; 5.2]), problems in subitising (OR 2.8 [2.7; 3.0]) and language development lags in the questionnaire of the nursery school teachers (OR 3.5 [3.3; 3.7]). Protective effects were an elevated graduation of the mother (OR 0.7 [0.7; 0.7]) or the father (OR 0.8 [0.7; 0.8]). Risk scores of the effects were defined. The corresponding predictive probability to different levels of risk scores was calculated. The true positive rate of the screening of language skills (HASE/KVS) in regard to special needs for language promotion was 0.95, the true negative rate was 0.72 and the -positive predictive value was 0.53. The school physician's findings of special needs for language promotion acted as gold standard. With the additional test (SETK 3-5) the positive predictive value improved to 0.9, if at least one of the subtests of the SETK 3-5 was not passed. The risk score-level corresponded with the pretest-probability and the consecutive positive predictive value of the screening of language skills. CONCLUSIONS: This study showed an adequate degree of test quality of the 2-level process in the new examination before primary school enrollment in Baden-Wuerttemberg (screening of language skills and additional test, if the screening is not passed). In addition children with special needs for language promotion had associated risks. Risk scores, that have been defined, offer an information tool to the school physicians concerning the positive predictive value of the screening of language skills without additional testing.

Influence of anthropometric features on graft diameter in ACL reconstruction.

BACKGROUND: There is a paucity of literature regarding the influence of anthropometric features on the hamstring graft obtained in ACL reconstruction. This study was undertaken to assess the influence of anthropometric measurements on the graft diameter obtained at ACL reconstruction surgery within the European population. We hypothesise that anthropometric features do influence graft thickness in ACL reconstruction. MATERIALS AND METHODS: Data from 121 consecutive patients who had undergone ACL reconstruction by the same surgeon using quadruple hamstring grafts were analysed. The body mass index (BMI), height and weight of these patients were correlated with the graft diameter obtained during surgery. Regression analysis was undertaken to assess the influence of individual anthropometric variables on the graft diameter. RESULTS: There were 121 patients with mean age of 32 years (14-55). There was a statistically significant positive correlation individually between the height and graft diameter (r = 0.38, p < 0.01) as well as between the body weight and graft diameter (r = 0.29, p < 0.01). However, when the body mass index was calculated, the correlation was not statistically significant (r = 0.08, p > 0.1). Regression analysis confirmed that BMI was not statistically significant as a predictor of hamstring graft diameter whereas height was statistically the most important predictor (F = 20.1; p < 0.01).This yielded the predictive equation, graft diameter = 4.5 + 0.02 x Ht (in cm). CONCLUSION: Although body mass index did not significantly correlate, body height may be a predictive variable in predicting the graft diameter in ACL reconstruction and provide useful pre operative information.

Keratolysis exfoliativa (dyshidrosis lamellosa sicca): a distinct peeling entity.

BACKGROUND: Keratolysis exfoliativa (KE), also known as dyshidrosis lamellosa sicca, is a palmoplantar dermatosis characterized by air-filled blisters and collarette desquamation. It has been regarded as a subtype of dyshidrotic eczema, a fungal infection or a dermatophytid reaction. KE may also resemble acral peeling skin syndrome and localized epidermolysis bullosa simplex. Although KE is a common disorder, it is a rarely reported and is an under-recognized dermatosis. OBJECTIVES: To delineate the characteristic features of KE. METHODS: We investigated the clinical, immunohistopathological, ultrastructural and molecular features of KE. Patients were included from the clinical records. Additional diagnostic research consisted of mutation analysis of the candidate genes TGM5, KRT5, KRT14, FLG, SPINK6 and SPINK9. RESULTS: A total of 24 patients with KE were identified, six with familial and 18 with sporadic KE. Lesions consisted of air-filled blisters only on palmoplantar skin, followed by collarette and lamellar peeling. Both light microscopy and electron microscopy showed cleavage and partially degraded corneodesmosomes within the stratum corneum, whereas immunofluorescence microscopy showed normal expression of corneodesmosomal components. No mutations were found in TGM5, KRT5/14 and SPINK6/9. There was no clear link with atopy or with FLG mutations. CONCLUSIONS: Our study suggests premature corneodesmolysis as the main pathological mechanism of this palmoplantar skin disorder. We conclude that KE appears to be a distinct peeling entity.

Frequency of subnormal hypoosmotic swelling tests increase with advancing age of the male.

PURPOSE: To determine if there is an increased frequency of abnormal hypoosmotic swelling (HOS) tests when testing semen in males of advanced reproductive age. METHODS: Ten-year retrospective review according to six age groups (< or = 29.9, 30-34.9, 35-39.9, 40-44.9, 45.0-49.9, and > or = 50). RESULTS: Compared to males < 35 years old, the frequency of HOS scores < 50% doubles in males 45-49.9 and quadruples in males > or = 50. CONCLUSIONS: Males with low HOS scores despite having no problem with fertilization of the oocytes rarely achieve a pregnancy because of embryo implantation defects unless intracytoplasmic sperm injection (ICSI) is performed. Thus at least one abnormality seen in sperm of males of advanced reproductive age is correctable by performing in vitro fertilization with ICSI.

The majority of males with subnormal hypoosmotic test scores have normal vitality.

PURPOSE: To determine if males with low hypoosmotic swelling (HOS) test scores may have normal vitality tests. METHODS: Retrospective nine-year review of initial semen analyses evaluating vitality and HOS tests. RESULTS: Only 12.5% (45/361) of males with low HOS test scores have low vitality. CONCLUSIONS: WHO seems to treat vitality and HOS as equal tests. We disagree and find that structural defects of the sperm membrane are much less common than functional impairment of the sperm membrane. Since a male with an HOS test score < 50% will rarely achieve a pregnancy with intercourse, intrauterine insemination, or IVF with conventional insemination it is important to check for the HOS test not viability because the HOS test can be easily corrected with ICSI.

Low hypoosmotic swelling test scores correlate better with lower percent motility than any other abnormal semen parameters.

PURPOSE: To determine if any single abnormal semen parameter is associated with low hypoosmotic swelling (HOS) test scores. METHODS: A retrospective review evaluating males with single sperm defects of sperm concentration, % progressive motility, morphology using strict criteria, and antisperm antibodies. The percentage of these males with HOS test scores < 50% was then determined. RESULTS: By far the abnormal semen parameter most associated with a subnormal HOS test was poor motility. CONCLUSIONS: Though we believe that the simple inexpensive HOS test should be performed routinely when performing semen analysis, it is especially important to evaluate in males with poor motility since simple intrauterine insemination will not allow pregnancies.

A combined active shape and mean appearance model for the reconstruction of segmental bone loss.

This study investigates the novel combination of an active shape and mean appearance model to estimate missing bone geometry and density distribution from sparse inputs simulating segmental bone loss of the femoral diaphysis. An active shape Gaussian Process Morphable model was trained on healthy right femurs of South African males to model shape. The density distribution was approximated based on the mean appearance of computed tomography images from the training set. Estimations of diaphyseal resections were obtained by probabilistic fitting of the active shape model to sparse inputs consisting of proximal and distal femoral data on computed tomography images. The resulting shape estimates of the diaphyseal resections were then used to map the mean appearance model to the patients' missing bone geometry, constructing density estimations. In this way, resected bone surfaces were estimated with an average error of 2.24 (0.5) mm. Density distributions were approximated within 87 (0.7) % of the intensity of the original target images before the simulated segmental bone loss. These results fall within the acceptable tolerances required for surgical planning and reconstruction of long bone defects.

Taking immunogenicity assessment of therapeutic proteins to the next level.

Therapeutic proteins provide innovative and effective therapies for numerous diseases. However, some of these products are associated with unwanted immunogenicity that may lead to clinical consequences such as reduced or loss of efficacy, altered pharmacokinetics (PK), general immune and hypersensitivity reactions, and neutralisation of the natural counterpart (e.g. the physiological hormone). Regulatory guidance on immunogenicity assessment needs to take into consideration a great diversity of products, indications and patient populations as well as constantly advancing manufacturing technologies. Such guidance needs to be sufficiently specific while, at the same time, allowing interactive discussion and adjusted benefit-risk weighing of each product on a case-by-case basis, e.g. for a unique treatment of a life threatening disease acceptable treatment risks may differ considerably from the ones in case of less serious disease. This theme was the focus of the international conference "Taking immunogenicity assessment of therapeutic proteins to the next level", held at the Paul-Ehrlich-Institut in Langen, Germany, on the 10-11. June 2010. The objectives of the conference were to highlight how the field could move from that of a mere description of risk factors to a system of risk assessment and mitigation, as well as an understanding of the impact of unwanted immunogenicity on the overall benefit/risk consideration for a medicinal product. More than 150 experts from industry, academia and regulatory authorities worldwide discussed the phenomenon of undesired immunogenicity from different perspectives. The conference focussed on issues relevant to three areas: (1) new European guidelines that are currently the subject of discussion; (2) testing strategies for immunogenicity assessment; and (3) scientific progress on the product-related factors that may contribute to the development of pathogenesis of immunogenicity, in particular in the field of protein aggregation and post-translational modifications. This report provides an overview of issues, insights, and conclusions that were discussed and achieved during the meeting.

Minimum velocity necessary for nonconventional projectiles to penetrate the eye: an experimental study using pig eyes.

To satisfy the Criminal Code of Canada's definition of a firearm, a barreled weapon must be capable of causing serious bodily injury or death to a person. Canadian courts have accepted the forensically established criteria of "penetration or rupture of an eye" as serious bodily injury. The minimal velocity of nonconventional ammunition required to penetrate the eye including airsoft projectiles has yet to be established. To establish minimal threshold requirements for eye penetration, empirical tests were conducted using a variety of airsoft projectiles. Using the data obtained from these tests, and previous research using "air gun" projectiles, an "energy density" parameter was calculated for the minimum penetration threshold of an eye. Airsoft guns capable of achieving velocities in excess of 99 m/s (325 ft/s) using conventional 6-mm airsoft ammunition will satisfy the forensically established criteria of "serious bodily injury." The energy density parameter for typical 6-mm plastic airsoft projectiles is 4.3 to 4.8 J/cm². This calculation also encompasses 4.5-mm steel BBs.

Aerosol insulin induces regulatory CD8 gamma delta T cells that prevent murine insulin-dependent diabetes.

Cellular immune hyporesponsiveness can be induced by the presentation of soluble protein antigens to mucosal surfaces. Most studies of mucosa-mediated tolerance have used the oral route of antigen delivery and few have examined autoantigens in natural models of autoimmune disease. Insulin is an autoantigen in humans and nonobese diabetic (NOD) mice with insulin-dependent diabetes mellitus (IDDM). When we administered insulin aerosol to NOD mice after the onset of subclinical disease, pancreatic islet pathology and diabetes incidence were both significantly reduced. Insulin-treated mice had increased circulating antibodies to insulin, absent splenocyte proliferation to the major epitope, insulin B chain amino acids 9-23, which was associated with increased IL-4 and particularly IL-10 secretion, and reduced proliferation to glutamic acid decarboxylase, another islet autoantigen. The ability of splenocytes from insulin-treated mice to suppress the adoptive transfer of diabetes to nondiabetic mice by T cells of diabetic mice was shown to be caused by small numbers of CD8 gamma delta T cells. These findings reveal a novel mechanism for suppressing cell-mediated autoimmune disease. Induction of regulatory CD8 gamma delta T cells by aerosol insulin is a therapeutic strategy with implications for the prevention of human IDDM.

Surface-chemistry-driven actuation in nanoporous gold.

Although actuation in biological systems is exclusively powered by chemical energy, this concept has not been realized in man-made actuator technologies, as these rely on generating heat or electricity first. Here, we demonstrate that surface-chemistry-driven actuation can be realized in high-surface-area materials such as nanoporous gold. For example, we achieve reversible strain amplitudes of the order of a few tenths of a per cent by alternating exposure of nanoporous Au to ozone and carbon monoxide. The effect can be explained by adsorbate-induced changes of the surface stress, and can be used to convert chemical energy directly into a mechanical response, thus opening the door to surface-chemistry-driven actuator and sensor technologies.