Optical limiting properties of surface functionalized nanodiamonds probed by the Z-scan method.

This work focuses on the optical limiting behavior of surface modified nanodiamonds (DNDs) namely, amino-terminated DNDs (DND-NH2) and hydrogen-terminated DNDs (DND-H). Their relevant nonlinear optical properties for optical limiting are compared to those of unfunctionalized DNDs. The optical limitation is characterized by means of nonlinear transmittance, Z-scan, and scattered intensity assessments when submitted to a nanosecond pulsed Nd:YAG laser operating at a wavelength of 532 nm. It is stated that the largest nonlinear attenuation is attributed to the DND-H system, whereas the exceedingly low threshold values for optical limiting for the DND-H and the DND-NH2 systems is attributed to their negative electron affinity character (NEA). Using Z-scan experiments, it is shown that nonlinear refraction combined with a significant nonlinear absorption predominates in the DND-H suspension, while the pure thermal origin of the nonlinear refractive index change is conjectured in the case of the DNDs. Besides, an amazing valley to peak profile was measured on DND - NH2indicating an unexpected positive sign of the nonlinear refraction coefficient. In addition, a stronger backscattered intensity signal is highlighted for the unfunctionalized DNDs through nonlinear scattering measurements.

A clickable NHC-Au(i)-complex for the preparation of stimulus-responsive metallopeptide amphiphiles.

We report the synthesis of an alkyne functionalised NHC-Au(i)-complex which is conjugated with amphiphilic oligopeptides using a copper(i) catalysed cycloaddition. The resulting Au(i)-metalloamphiphiles are shown to self-assemble into charge-regulated stimulus-responsive supramolecular polymers in water via a weakly cooperative polymerisation mechanism.

Folding induced supramolecular assembly into pH-responsive nanorods with a protein repellent shell.

We report the synthesis of ABA' triblock peptide-polysarcosine-peptide conjugates featuring two complementary phenylalanine-histidine pentapeptide strands A/A'. These sequences encode for antiparallel ß-sheet formation into folded conjugates, which promote the self-assembly into polysarcosine-shielded core-shell nanorods. These do not cause aggregation of serum proteins in human blood plasma underlining an enhanced stability.

Optical properties of functionalized nanodiamonds.

Detonation nanodiamonds exhibit strong nonlinear optical properties depending on their electronic properties. In the present paper, the nanodiamond functional groups are chemically modified to obtain nanodiamonds with primary amines on their surface. The optical properties of such nanodiamonds placed in water suspensions are studied and compared with the one of classical detonation nanodiamonds. Transmission, scattering and Z-scan experiments are performed for two different wavelengths (532 nm and 1064 nm). A lower threshold for optical limiting associated to more pronounce non-linear optical effects is detected at the wavelength of 1064 nm compared to the one at 532 nm. This effect may be due to a stronger nonlinear backscattering behavior at 1064 nm. Moreover, a striking result obtained from the Z-scan experiments reveals a completely different behavior of the functionalized nanodiamonds for both wavelengths. This result is discussed in regard to the electronic properties of the material and possible charge transfer.

Closing the Gap: Mouse Models to Study Adhesion in Secondary Palatogenesis.

Secondary palatogenesis occurs when the bilateral palatal shelves (PS), arising from maxillary prominences, fuse at the midline, forming the hard and soft palate. This embryonic phenomenon involves a complex array of morphogenetic events that require coordinated proliferation, apoptosis, migration, and adhesion in the PS epithelia and underlying mesenchyme. When the delicate process of craniofacial morphogenesis is disrupted, the result is orofacial clefting, including cleft lip and cleft palate (CL/P). Through human genetic and animal studies, there are now hundreds of known genetic alternations associated with orofacial clefts; so, it is not surprising that CL/P is among the most common of all birth defects. In recent years, in vitro cell-based assays, ex vivo palate cultures, and genetically engineered animal models have advanced our understanding of the developmental and cell biological pathways that contribute to palate closure. This is particularly true for the areas of PS patterning and growth as well as medial epithelial seam dissolution during palatal fusion. Here, we focus on epithelial cell-cell adhesion, a critical but understudied process in secondary palatogenesis, and provide a review of the available tools and mouse models to better understand this phenomenon.

Ovarian stimulation in ART - Unwinding pressing issues.

Conventional controlled ovarian stimulation (cCOS) can cause significant discomfort, including ovarian hyperstimulation syndrome (OHSS). Clearly, management of OHSS and poor responder patients requires new strategies to overcome these problems and facilitate the birth of a healthy child with the fewest stimulation cycles. Several alternative methods have been developed. Non-conventional controlled ovarian stimulation (non-cCOS) is based on low-dose stimulation regimens and is often termed "light", "soft", "mini", "minimal", "mild", "low cost", or "low dose IVF". Non-controlled ovarian stimulation therapies (non-COS) include natural cycle IVF or a mixture between non-controlled and non-cCOS, termed "modified natural IVF" or "antiestrogen/aromatase inhibitor/low dose FSH-cycles", in which cycles are monitored but not controlled. These approaches promise to reduce the physical, emotional, and financial burden of IVF therapy while maintaining acceptable pregnancy rates. Such approaches might reduce the risk of OHSS. However, the overall cost per baby increases due to the higher number of stimulation cycles required, and the inconvenience of ovum pick-up still remains. The primary focus should be to obtain several good quality blastocysts after a single cCOS cycle. Thus, adequate numbers of mature oocytes are mandatory. What is more difficult and expensive for patients: several non-COS/non-cCOS cycles to obtain a baby or a single cCOS cycle with a high probability to obtain more than one child? Classic cCOS using the GnRH agonist long protocol followed by single embryo transfer (SET) at the blastocyst stage and aseptic vitrification of surplus embryos optimizes the IVF outcome. This strategy, combined with outpatient management in the case of OHSS, minimizes inconvenience and risks of OHSS. Accumulation cycles (AC) by repeated COS with subsequent freezing of blastocysts, combined with preimplantation genetic screening (PGS), is a promising new approach for low responders, especially in cases of advanced maternal age (AMA).

Implications of Blood Type for Ovarian Reserve and Infertility - Impact on Oocyte Yield in IVF Patients.

Introduction: Diminished ovarian reserve (DOR) has been linked to certain subpopulations and distinct gene polymorphisms. It has even been hypothesized that the AB0 blood group system could be linked to ovarian reserve (OR) as reflected by early follicular phase follicle stimulating hormone (FSH) levels. Although estimation of OR is routinely done using levels of anti-Müllerian hormone (AMH), FSH, estradiol or inhibin B, the diagnostic accuracy of these markers is often limited. The aim of this study was to evaluate whether there is any correlation between IVF patients' AB0 blood group system and ART outcome. Methods: In this retrospective observational single-center study we investigated the outcome of 1889 IVF cycles carried out between 2005 and 2012 with regard to blood type and OR in different age groups (21-36 years and 37-43 years). The number of cumulus oocyte complexes (COCs) and metaphase II oocytes obtained after ovarian stimulation, fertilization rate (FR), pregnancy rate (PR) and birth rate (BR) were evaluated with respect to maternal age (21-36 and 37-43 years, respectively). Results: We found no significant differences in the average number of COCs after ovum pick-up in either of the age groups. Moreover, the mean number of MII oocytes and 2PN stages were similar for all blood type groups. As regards IVF outcome measured in terms of PR and BR, no significant differences were observed between the different blood groups. In conclusion, no correlation was found between blood type and female fertility. Discussion: The most precise definition of OR is determining the number of competent oocytes. Based on the finding of our study, the hypothesis that there is a correlation between OR and AB0 blood group system can be dismissed for Caucasian IVF patients.

Continuous engineering of nano-cocrystals for medical and energetic applications.

Cocrystals, solid mixtures of different molecules on molecular scale, are supposed to be tailor made materials with improved employability compared to their pristine individual components in domains such as medicine and explosives. In medicine, cocrystals are obtained by crystallization of active pharmaceutical ingredients with precisely chosen coformers to design medicaments that demonstrate enhanced stability, high solubility, and therefore high bioavailability and optimized drug up-take. Nanoscaling may further advance these characteristica compared to their micronsized counterparts - because of a larger surface to volume ratio of nanoparticles. In the field of energetic materials, cocrystals offer the opportunity to design smart explosives, combining high reactivity with significantly reduced sensitivity, nowadays essential for a safe manipulation and handling. Furthermore, cocrystals are used in ferroelectrics, non-linear material response and electronic organics. However, state of the art batch processes produce low volume of cocrystals of variable quality and only have produced micronsized cocrystals so far, no nano-cocrystals. Here we demonstrate the continuous preparation of pharmaceutical and energetic micro- and nano-cocrystals using the Spray Flash Evaporation process. Our laboratory scale pilot plant continuously prepared up to 8 grams per hour of Caffeine/Oxalic acid 2:1, Caffeine/Glutaric acid 1:1, TNT/CL-20 1:1 and HMX/Cl-20 1:2 nano- and submicronsized cocrystals.

The time aspect in storing vitrified blastocysts: its impact on survival rate, implantation potential and babies born.

STUDY QUESTION: Does the storage time of vitrified human blastocysts negatively impact their survival, the implantation potential of embryos or the malformation rate of babies born? SUMMARY ANSWER: There was no evidence that storage times of up to 6 years after vitrification (VIT) had a negative impact on blastocyst survival, the implantation potential of embryos or the malformation rate of babies born. WHAT IS KNOWN ALREADY: Although several thousand children have been born after blastocyst VIT, many aspects of this technique remain to be elucidated. New applications, such as fertility preservation, lead to long storage times of vitrified gametes or embryos but it remains to be determined if these vitrified embryos are stable over time. STUDY DESIGN, SIZE, DURATION: A retrospective study including 603 transfers was conducted between January 2009 and April 2012. Blastocysts were vitrified using a closed system. PARTICIPANTS/MATERIALS, SETTING, METHODS: All patients underwent the transfer of aseptically vitrified/warmed blastocysts in a cryo-cycle. A total of 1077 blastocysts were transferred. Survival rates (SRs), implantation potential, birth rates and characteristics of the children born were evaluated. MAIN RESULTS AND THE ROLE OF CHANCE: We found that the storage of vitrified blastocysts in aseptic conditions neither impaired blastocyst viability (SR after warming during the first year of storage was 83.0% compared with 83.1% after 5-6 years of storage: NS) nor decreased pregnancy rates (clinical pregnancy rate after 1 year of storage was 40.0 versus 38.5% after 6 years: NS). In addition, no increase in the malformation rate over time was observed. LIMITATIONS, REASONS FOR CAUTION: Our study only included the transfer of blastocysts which had been vitrified aseptically (i.e. using a closed system). Therefore, our results might not be applicable to 'open' VIT systems. The long-term follow-up of children born will be necessary to confirm our findings. WIDER IMPLICATIONS OF THE FINDINGS: The results suggest that vitrified human blastocysts can be stored for long periods of time without significant negative consequences for the offspring. Therefore, the method should be of benefit to those patients who need to consider taking measures for fertility preservation. STUDY FUNDING/COMPETING INTEREST(S): No external funding was sought for this study and the authors have no conflict of interest to declare.

Ellipsometry with polarisation analysis at cryogenic temperatures inside a vacuum chamber.

In this paper we describe a new variant of null ellipsometry to determine thicknesses and optical properties of thin films on a substrate at cryogenic temperatures. In the PCSA arrangement of ellipsometry the polarizer and the compensator are placed before the substrate and the analyzer after it. Usually, in the null ellipsometry the polarizer and the analyzer are rotated to find the searched minimum in intensity. In our variant we rotate the polarizer and the compensator instead, both being placed in the incoming beam before the substrate. Therefore the polarisation analysis of the reflected beam can be realized by an analyzer at fixed orientation. We developed this method for investigations of thin cryogenic films inside a vacuum chamber where the analyzer and detector had to be placed inside the cold shield at a temperature of T ≈ 90 K close to the substrate. All other optical components were installed at the incoming beam line outside the vacuum chamber, including all components which need to be rotated during the measurements. Our null ellipsometry variant has been tested with condensed krypton films on a highly oriented pyrolytic graphite substrate (HOPG) at a temperature of T ≈ 25 K. We show that it is possible to determine the indices of refraction of condensed krypton and of the HOPG substrate as well as thickness of krypton films with reasonable accuracy.

Direct volumetric flow cytometric quantitation of CD34+ stem and progenitor cells.

OBJECTIVES: In this study, we compared a classic single-platform (SP) method applying beads for enumeration of CD45+ or CD34+ cells with a new device allowing direct volumetric measurements of stem and progenitor cells. BACKGROUND: Following apheresis and cyropreservation, the precise enumeration of CD34+ cells as key parameter of graft quality is mandatory for the clinical course after transplantation. Currently, flow cytometry with SP technique represents the 'gold standard' for such determinations. METHODS/MATERIALS: Fresh samples, 14 from mobilised peripheral blood (PB), 9 from apheresis products (AP) and 13 samples from frozen-thawed (FT) haematopoietic progenitor cell grafts, were analysed for CD34+ cells, CD45+ cells, and in frozen-thawed samples for viability by a bead-based flow cytometric method and in parallel by a direct, volumetric flow cytometric method. RESULTS: Comparison of CD34+ analyses revealed a significant correlation (P < 0·01) for each material between both techniques with r = 0·95 (PB), r = 0·933 (AP) and r = 0·929 (FT). Also, for analysis of CD45+ cells µL(-1) , the measured numbers evaluated with the different techniques did not significantly differ for all three materials analysed. In frozen-thawed samples, the analysis of viability was comparable for both techniques. CONCLUSIONS: The results of this study demonstrate that a direct volumetric analysis of CD34+ cells µL(-1) or CD45+ cells µL(-1) is feasible. This technique represents a simple and economical approach for standardisation of progenitor and stem cell analyses.

Adnexal Torsion in Pregnancy after Assisted Reproduction - Case Study and Review of the Literature.

Purpose: Aim of the study was to investigate the incidence, progress, management and outcome of adnexal torsion after controlled ovarian hyperstimulation in embryo transfer cycles. Materials and Method: A retrospective analysis was done of 1007 patients of a private IVF centre. The literature on adnexal torsion is reviewed. Results: In the literature, the incidence of adnexal torsion after assisted reproductive technologies (ART) is given as around 0.2 %. A significant increase of up to 33 % has been reported for cases with additional ovarian hyperstimulation syndrome (OHSS) and in pregnant women. In our retrospective analysis of 1007 women (incidence 0.46 %) with 1411 fresh embryo transfer cycles, we found an incidence of 0.35 % per embryo transfer. All adnexal torsions were treated by laparoscopic derotation to preserve fertility. All 5 cases with torsion were pregnant, 2 patients had mild OHSS. We recorded 3 term deliveries, 1 induced abortion for sirenomelia, and 1 missed abortion. Conclusion: Adnexal torsion must be kept in mind after hyperstimulation and embryo transfer, especially when pregnancy or OHSS is also present. With early diagnosis, it should be possible to preserve fertility using laparoscopic derotation.

MRI-based pre-planning in patients with cervical cancer treated with three-dimensional brachytherapy.

OBJECTIVE: The aim of this study was to analyse the feasibility and determine the benefits of MRI-based pre-planning with CT/MRI data fusion in patients with cervical cancer treated with radical radiotherapy. METHODS: Patients underwent MRI examination prior to external beam radiotherapy and prior to the first and fourth fraction of brachytherapy with applicators in place. Insertion of applicators at the radiology department was performed under paracervical anaesthesia. The benefit of MRI pre-planning was determined by comparing conventional treatment planning with dose specification to "point A" and dose specification to 90% of the high-risk clinical target volume (HR-CTV D90). Tolerance of MRI evaluation with applicators, coverage of HR-CTV and dose-volume parameters for organs at risk (OAR) has been assessed in 42 brachytherapy procedures. RESULTS: Insertion of applicators at the radiology department was successful in all patients and there were no complications. The target dose was higher for MRI planning than for conventional planning (5.3 Gy vs 4.5 Gy). Maximum doses in the bladder and rectum were significantly lower (p<0.05) for MRI planning than for the conventional approach (6.49 Gy vs 7.45 Gy for bladder; 4.57 Gy vs 5.06 Gy for rectum). We found no correlation between the International Commission on Radiation Units (ICRU) point dose for OAR and the maximum dose in OAR. Nevertheless, a strong correlation between the maximum dose in OAR and the minimal dose in a volume of 2 cm(3) has been observed. CONCLUSION: MRI-based pre-planning with consecutive CT/MRI data fusion is feasible and safe, with the advantage of increasing the dose to the tumour and decreasing the dose to the organs at risk.

Sunitinib in metastatic thymic carcinomas: laboratory findings and initial clinical experience.

BACKGROUND: Thymic carcinoma (TC) is a rare aggressive tumour. Median survival with current treatments is only 2 years. Sunitinib is a multi-targeted tyrosine kinase inhibitor that has shown benefit in various other cancers. METHODS: Laboratory analyses of snap-frozen tumour tissues were performed to detect activation and genetic mutations of receptor tyrosine kinases (RTKs) in TC samples. On the basis of molecular analyses showing activation of multiple RTKs in their tumour, four patients with metastatic TCs refractory to conventional therapies were treated with sunitinib according to standard protocols. RESULTS: RTK analysis in three of the patients showed activation of multiple RTKs, including platelet-derived growth factor-beta and vascular endothelial growth factor 3. Mutations of EGFR, c-KIT, KRAS, and BRAF genes were not found. Administration of sunitinib yielded a partial remission (lasting 2 to 18+ months) according to the RECIST criteria in three patients and stable disease with excellent metabolic response in 18F-FDG-PET in another one. The overall survival with sunitinib treatment ranges from 4 to 40+ months. Withdrawal of the drug in one patient prompted rapid tumour progression that could be controlled by re-administration of sunitinib. CONCLUSIONS: Sunitinib is an active treatment for metastatic TC. A panel of molecular analyses may be warranted for optimal patient selection.

Can guidelines improve referral to elective surgical specialties for adults? A systematic review.

AIM: To assess effectiveness of guidelines for referral for elective surgical assessment. METHOD: Systematic review with descriptive synthesis. DATA SOURCES: Medline, EMBASE, CINAHL and Cochrane database up to 2008. Hand searches of journals and websites. SELECTION OF STUDIES: Studies evaluated guidelines for referral from primary to secondary care, for elective surgical assessment for adults. OUTCOME MEASURES: Appropriateness of referral (usually measured as guideline compliance) including clinical appropriateness, appropriateness of destination and of pre-referral management (eg, diagnostic investigations), general practitioner knowledge of referral appropriateness, referral rates, health outcomes and costs. RESULTS: 24 eligible studies (5 randomised control trials, 6 cohort, 13 case series) included guidelines from UK, Europe, Canada and the USA for referral for musculoskeletal, urological, ENT, gynaecology, general surgical and ophthalmological conditions. Interventions varied from complex ("one-stop shops") to simple guidelines. Four randomized control trials reported increases in appropriateness of pre-referral care (diagnostic investigations and treatment). No evidence was found for effects on practitioner knowledge. Mixed evidence was reported on rates of referral and costs (rates and costs increased, decreased or stayed the same). Two studies reported on health outcomes finding no change. CONCLUSIONS: Guidelines for elective surgical referral can improve appropriateness of care by improving pre-referral investigation and treatment, but there is no strong evidence in favour of other beneficial effects.

Preparation of explosive nanoparticles in a porous chromium(III) oxide matrix: a first attempt to control the reactivity of explosives.

This paper reports the first attempt to control the combustion and the detonation properties of a high explosive through its structure. A porous chromium(III) oxide matrix produced by the combustion of ammonium dichromate was infiltrated by hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX). The structure of the Cr(2)O(3) matrix was studied by both scanning and transmission electron microscopy (SEM, TEM); the Cr(2)O(3)/RDX nanocomposites were characterized by nitrogen adsorption. A mathematical model based on these techniques was used to demonstrate that the Cr(2)O(3) matrix encloses and stabilizes RDX particles at the nanoscale. The decomposition process of the nanocomposites was investigated by atomic force microscopy (AFM). The reactivity and sensitivity of the nanocomposites were studied by impact and friction tests, differential scanning calorimetry (DSC), time-resolved cinematography and detonation experiments, and were correlated with their structure. The size of RDX nanoparticles and their distribution in the Cr(2)O(3) matrix have an important influence on their reactivity. The reactive properties of nanostructured RDX differ significantly from those of classical micron-sized RDX. For instance, the melting point disappears and the decomposition temperature is significantly lowered. The quantization of the explosive particles in the Cr(2)O(3) matrix decreases the sensitivity to mechanical stress and allows controlling the decomposition mode-i.e. combustion versus detonation.

The decay accelerating factor mutation I197V found in hemolytic uraemic syndrome does not impair complement regulation.

Hemolytic uremic syndrome is the clinical triad of thrombocytopenia, microangiopathic hemolytic anaemia and acute renal failure. Cases not associated with a preceding Shiga-like toxin producing Escherichia coli are described as atypical HUS (aHUS). Approximately 50% of patients with aHUS have mutations in one of three complement regulatory proteins, Factor H (CFH), membrane cofactor protein (MCP;CD46) or factor I (IF). A common feature of these three proteins is that they regulate complement by cofactor activity. Decay accelerating factor (DAF; CD55) regulates the complement system by disassociating the alternative and classical pathway convertases. Like CFH and MCP, the gene for DAF lies within the regulators of complement activation (RCA) gene cluster at 1q32. In 1998, we described linkage to this region in families with aHUS which led to the discovery of mutations in CFH and MCP. We therefore genotyped DAF in a panel of 46 aHUS patients including families with linkage to the RCA cluster. A mutation, I197V, was identified in one patient with familial HUS which was not found in 100 healthy controls. Molecular modelling of this mutation shows that the I197V mutation does not reside in an area which would be predicted to be important in decay accelerating activity. The expression of I197V on EBV-transformed B lymphocytes was equivalent to that of wild type controls. There was no significant decrease in decay acceleration activity of the recombinantly produced I197V mutant compared with wild type, as measured by a complement-mediated lytic assay. In conclusion, this study, identifies only one mutation in DAF in 46 patients with aHUS. This mutation, I197V, does not impair complement regulation and cannot be implicated in the pathogenesis of aHUS in this patient. This suggests that the complement regulatory abnormality in aHUS is principally one of deficient cofactor activity rather than of decay acceleration activity.

Immigrant women family caregivers in Canada: implications for policies and programmes in health and social sectors.

Migration has become a profound global phenomenon in this century. In Canada, uncoordinated policies, including those related to immigration, resettlement, employment, and government funding for health and social services, present barriers to immigrant women caregivers. The purpose of this paper is to share relevant insights from individual and group interviews with immigrant women family caregivers, service providers and policy influencers, and discuss these in relation to immigration, health and social policy, and programme trends in Canada. The present authors conducted individual interviews with immigrant women family caregivers (n = 29) in phase 1, followed by two group interviews with women family caregivers (n = 7), and two group interviews with service providers and policy-makers (n = 15) in phase 2. Using an inductive approach, the authors employed thematic content data analysis. Immigrant women experienced barriers to health and social services similar to Canadian-born family caregivers, particularly those who have low incomes, jobs with limited flexibility and heavy caregiving demands. These immigrant women family caregivers avoided certain formal services for a variety of reasons, including lack of cultural sensitivity. However, their challenges were compounded by language, immigration and separation from family in the home country. The identified barriers to support reinforce the importance of modifying and expanding policies and programmes affecting immigrant women's ability to care for family members with illnesses or disabilities within the context of Canadian society. Participants recommended changes to policies and programmes to deal with information, transportation, language, attitudinal and network barriers. The various barriers to services and programmes which were experienced by immigrant women caregivers underscore the importance of reviewing policies affecting immigration, caregiving, and access to health and social services. Intersectoral collaboration among agencies is essential to reduce the barriers identified in the present study, and to establish services which are linguistically and culturally appropriate.