Triplet fusion upconversion nanocapsules for volumetric 3D printing.

Three-dimensional (3D) printing has exploded in interest as new technologies have opened up a multitude of applications1-6, with stereolithography a particularly successful approach4,7-9. However, owing to the linear absorption of light, this technique requires photopolymerization to occur at the surface of the printing volume, imparting fundamental limitations on resin choice and shape gamut. One promising way to circumvent this interfacial paradigm is to move beyond linear processes, with many groups using two-photon absorption to print in a truly volumetric fashion3,7-9. Using two-photon absorption, many groups and companies have been able to create remarkable nanoscale structures4,5, but the laser power required to drive this process has limited print size and speed, preventing widespread application beyond the nanoscale. Here we use triplet fusion upconversion10-13 to print volumetrically with less than 4 milliwatt continuous-wave excitation. Upconversion is introduced to the resin by means of encapsulation with a silica shell and solubilizing ligands. We further introduce an excitonic strategy to systematically control the upconversion threshold to support either monovoxel or parallelized printing schemes, printing at power densities several orders of magnitude lower than the power densities required for two-photon-based 3D printing.

Evidence of Antineutrinos from Distant Reactors Using Pure Water at SNO.

The SNO+ Collaboration reports the first evidence of reactor antineutrinos in a Cherenkov detector. The nearest nuclear reactors are located 240 km away in Ontario, Canada. This analysis uses events with energies lower than in any previous analysis with a large water Cherenkov detector. Two analytical methods are used to distinguish reactor antineutrinos from background events in 190 days of data and yield consistent evidence for antineutrinos with a combined significance of 3.5σ.

Management of perianal abscesses in infants without general anaesthesia: a systematic review of the literature.

Perianal abscesses are a common surgical presentation in infants. Historically, general anaesthesia (GA) has been used to facilitate incision and drainage, with or without exploration for a fistula-in-ano (FIA). This review aims to assess outcomes following management of perianal abscesses without GA in infants less than 24 months old. We aim to identify the success of management without GA. Using PRISMA guidelines, studies were identified from MEDLINE, EMBASE and PubMed. Studies including infants less than 24 months with perianal abscesses managed without GA were reviewed. The primary outcome was the number of patients requiring GA following initial management without GA. Secondary outcomes included rates of recurrent perianal abscesses, rates of progression to FIA and time to cure. Nine studies, involving 1049 infants less than 24 months old met inclusion criteria. A total of 1039 (99.0%) were males. Study design consisted of one prospective case series of 18 patients, and eight retrospective cohort studies. There were no randomized control trials. A total of 1037 (98.9%) patients were initially managed without GA. Of these, 59 (5.6%) were documented to subsequently require a general anaesthetic. Treatment modalities included antibiotics, regular baths, needle aspiration, incision and drainage under local anaesthesia, hainosankyuto and fibroblast growth factor. A total of 790 (75.3%) healed primarily without further intervention. A total of 243 (23.2%) were documented to have a recurrence or progression to FIA. All patients who required a subsequent general anaesthetic had progressed to FIA. Despite the lack of well-designed prospective studies, existing evidence supports management of perianal abscesses without initial GA in infants, with more than 75% healing completely. Further research aimed at standardizing care and confirming the safety and efficacy of initial non-operative management are warranted, and may potentially reduce the number of unnecessary initial and subsequent clinical interventions.

Analysis of Midesophageal Biopsies Increases Sensitivity of Detection of Eosinophilic Esophagitis.

Eosinophilic esophagitis (EoE) is defined by the presence of abundant eosinophils in the squamous epithelium of the esophagus. There has been remarkable progress recently in the understanding of the pathogenesis, diagnosis, and treatment of EoE.1 Because undiagnosed EoE leads to an increase in fibrostenotic complications including strictures, timely diagnosis is critical.2.

Triplet Fusion Upconversion Nanocapsule Synthesis.

Triplet fusion upconversion (UC) allows for the generation of one high energy photon from two low energy input photons. This well-studied process has significant implications for producing high energy light beyond a material's surface. However, the deployment of UC materials has been stymied due to poor material solubility, high concentration requirements, and oxygen sensitivity, ultimately resulting in reduced light output. Toward this end, nanoencapsulation has been a popular motif to circumvent these challenges, but durability has remained elusive in organic solvents. Recently, a nanoencapsulation technique was engineered to tackle each of these challenges, whereupon an oleic acid nanodroplet containing upconversion materials was encapsulated with a silica shell. Ultimately, these nanocapsules (NCs) were durable enough to enable triplet fusion upconversion-facilitated volumetric three-dimensional (3D) printing. By encapsulating upconversion materials with silica and dispersing them in a 3D printing resin, photopatterning beyond the surface of the printing vat was made possible. Here, video protocols for the synthesis of upconversion NCs are presented for both small-scale and large-scale batches. The outlined protocols serve as a starting point for adapting this encapsulation scheme to multiple upconversion schemes for use in volumetric 3D printing applications.

Synergistic effects of genetic beta cell dysfunction and maternal glucose intolerance on offspring metabolic phenotype in mice.

AIMS/HYPOTHESIS: Diabetes in pregnancy is linked to development of obesity in the offspring, but the mechanisms are not fully understood. Gestational diabetes mellitus (GDM) occurs when beta cells are unable to compensate for the normal insulin resistance of late pregnancy. In this study, we used a murine model of beta cell dysfunction to examine the effects of maternal GDM on phenotype in male offspring with and without an inherited predisposition for beta cell dysfunction. METHODS: Beta cell-specific aryl-hydrocarbon receptor nuclear translocator-null (ßArnt) mice develop GDM from beta cell dysfunction. ßArnt and control female mice were used to induce GDM and non-diabetic pregnancies, respectively. RESULTS: Offspring from GDM pregnancies became spontaneously obese on a normal-chow diet. They were heavier than offspring from non-diabetic pregnancies, with increased body fat. Respiratory exchange ratio (RER) was higher, indicating decreased capacity to switch to lipid oxidation. Metabolic rate in GDM offspring was decreased prior to onset of obesity. The phenotype was more pronounced in ßArnt GDM offspring than in GDM offspring of control genotype, demonstrating an interaction between genotype and pregnancy exposure. ßArnt GDM offspring had increased hypothalamic neuropeptide Y (Npy) and decreased pro-opiomelanocortin (Pomc) expression. Weight, body fat, insulin sensitivity and RER in all mice, and hypothalamic Npy in ßArnt mice were significantly correlated with AUC of maternal late pregnancy glucose tolerance tests (p < 0.01), but not with litter size, maternal weight, triacylglycerol or pre-pregnancy glycaemia. CONCLUSIONS/INTERPRETATION: In ßArnt mice, exposure to GDM and inheritance of genetic beta cell dysfunction had additive effects on male offspring obesity; severity of the offspring phenotype correlated with maternal glycaemia.

A new, passive dosemeter for gamma, beta and neutron radiations.

The Defence Science and Technology Laboratory (Dstl) provides personal radiation dosimetry to the UK Ministry of Defence. Dstl has recently developed a dosemeter that is based on a combination of thermoluminescent and etched-track detectors. The Dstl Combined Dosemeter is capable of assessing doses due to photons, beta particles and neutrons. This paper presents the laboratory type testing results for the Combined Dosemeter, and also describes the procedure for calibrating the dosemeter for use in workplace neutron fields. The Combined Dosemeter meets the type test requirements that are relevant to its intended applications, and gives neutron doses that are within 50% of the true dose in the workplaces in which it is used, even when the wearer has the potential to be exposed to a variety of neutron spectra (e.g. on board nuclear-powered submarines).

Tumor cells transfected with a bacterial heat-shock gene lose tumorigenicity and induce protection against tumors.

The gene encoding a highly immunogenic mycobacterial heat-shock protein (hsp65) was transfected into the murine macrophage tumor cell line J774. The resulting hsp65-expressing cells (J774-hsp65) were no longer able to produce tumors in syngeneic mice. This loss of tumorigenicity was not mediated through T cells since the transfected cells did not produce tumors in athymic mice. If mice are first immunized with the J774-hsp65 cells and then challenged with the parent J774 cells, the mice do not develop tumors, indicating that the presence of the mycobacterial hsp65 protein greatly enhances immunological recognition of unique structures expressed by the parent tumor cells. This is further confirmed by the demonstration in vitro of T cells derived from J774-hsp65-immunized mice that are cytotoxic for the parent J774 cells. The results provide the basis for a novel strategy for enhancing the immunological recognition and decreasing the tumorigenicity of transformed cells.

Monitoring of radon gas in caves of the Yorkshire Dales, United Kingdom.

A number of vocational training courses are held in caves in the Yorkshire Dales region of the United Kingdom. The instructors and students involved in these courses have the potential to be exposed to enhanced levels of radon ((222)Rn) and its progeny as a result of their occupations. A prior radiological risk assessment for the training courses recommended that an environmental monitoring programme be carried out to establish the radon concentrations in the caves, and that the caving instructors wear personal radon dosemeters. Radon gas concentrations varied seasonally, being at their highest in summer and their lowest in winter. The lowest result was 40  Bq m(-3) recorded in Lower Longchurn cave during winter, whilst the highest result was 4440  Bq m(-3) recorded in Crackpot cave during the summer. As the individuals involved in the caving are entering atmospheres with radon gas concentrations in excess of 400  Bq m(-3), the Ionising Radiation Regulations 1999 (GB Parliament 2000 Ionising Radiations Regulations 1999 (London: Stationary Office) SI 1999/3232) apply. A system of work is therefore in place to control exposure to radon. This system of work stipulates an initial dose investigation level of 1 mSv, a second dose investigation level of 2 mSv and an annual dose limit of 6 mSv. The highest annual dose recorded to date is 2.2 mSv, although the average (median) annual dose is only 0.5 mSv.

Pre-irradiation and post-irradiation fading of the Harshaw 8841 TLD in different environmental conditions.

The pre-irradiation and post-irradiation fading of a commercially available LiF:Mg,Cu,P thermoluminescent detector (TLD)-the Harshaw 8841 TLD-have been assessed. The Harshaw 8841 TLD comprises three TLD-700H chips (99.7% 7LiF and 0.03% 6LiF by weight) and one TLD-600H chip (4.4% 7LiF and 95.6% 6LiF by weight). Pre-irradiation and post-irradiation fading were measured for storage times up to 164 d and three different storage temperatures (-8, 25 and 50 degrees C). Dosemeters were irradiated in a mixed photon-neutron field so that the fading behaviour of the photon and neutron signals could be studied. The TLD-700H and TLD-600H chips exhibited complex changes in sensitivity and signal that depended on storage time, storage temperature and the type of radiation to which the chips had been exposed. However, the magnitudes of these changes in sensitivity and signal were relatively small. TLD-600H and TLD-700H, therefore, exhibit good stability of sensitivity and signal.

Effect of an injectable trace mineral at the initiation of a 14 day CIDR protocol on heifer performance and reproduction.

Three experiments were conducted at separate locations to determine the effects of a trace mineral injection (TMI), Multimin 90, on heifer performance and reproduction. In Exp. 1, [spring-born, Angus, n = 93, body weight (BW) = 428 ± 45.2 kg], Exp. 2 (spring-born, Angus × Simmental, n = 120, BW = 426 ± 54.0 kg), and Exp. 3 (fall-born, commercial Angus, n = 199, BW = 345 ± 39.7 kg) heifers were stratified by BW within experiment and assigned to 1 of 2 treatments: a control, saline injection, or TMI at a dose of 1 mL/68 kg BW. Free choice mineral, containing Cu, Mn, Se, and Zn formulated to meet or exceed NRC recommendations, was supplemented to heifers. Injections were given 33 d prior to breeding at the initiation of a 14-d controlled internal drug release (CIDR)-prostaglandin protocol. There was no difference (P ≥ 0.37) in BW during Exp. 1. Additionally, there was no difference (P ≥ 0.52) in body condition score (BCS) at initiation or at artificial insemination (AI) and final pregnancy confirmation in Exp. 1; however, a greater (P = 0.03) BCS was noted for control heifers at breeding. Pregnancy rates to timed AI and overall pregnancy rates were also similar (P ≥ 0.74) regardless of treatment. During Exp. 2, BCS and BW did not differ (P ≥ 0.44) across treatments. There was a tendency (P = 0.07) for TMI heifers to have an increased AI pregnancy rate (62 vs. 45%) compared with control heifers despite no difference (P = 0.51) in overall pregnancy rate. In Exp. 3, BW was not different (P ≥ 0.39) across all time points. Also, BCS did not differ (P ≥ 0.45) at initiation, AI, or final pregnancy conformation. Interestingly, there was a tendency (P = 0.10) for TMI heifers to have an increased BCS at the time of breeding compared with control heifers. However, there were no differences (P ≥ 0.50) in AI and overall pregnancy rates. In 1 of 3 experiments, an injectable trace mineral administered 33 d prior to the breeding season in conjunction with a 14-d CIDR protocol, tended to increased AI conception rates of heifers even when adequate trace mineral supplement was provided. The variable response observed across experiments may be caused by differences in breed, calving season, mineral sources, and management strategies.

The occurrence of congenital heart defects in an inbred herd of pigs in Australia.

OBJECTIVE: To report on the first case of congenital heart defects in pigs in Australia. DESIGN: Retrospective analysis of case records from an inbred herd of "Westran" pigs at the University of Sydney, between January 2001 and December 2004. Detailed gross and histological examination of 15 hearts from pigs that had died or were euthanased in 2004. CASE DETAILS: The necropsy records from a population of 471 pigs that had died (106 pigs) or were euthanased for research purposes (365 pigs) were analysed and the incidence of heart defects recorded, together with basic demographic data. No attempts were made to diagnose the condition in live pigs. RESULTS: Congenital heart defects were diagnosed in 6.4% of pigs but this is likely to be an underestimate of the incidence of the deformity. Eighteen pigs died on the farm as a result of the defect, and 12 pigs were diagnosed with the defect as an incidental finding. The most common abnormality seen at necropsy was a sac-like dilatation on the right lateral surface of the right atrium. This was associated with secondary deformity and hypoplasia of the adjacent left ventricle, interventricular region and part of the right ventricle. All hearts showed atrial septal defects of varying size. CONCLUSION: This is the first reported case of congenital heart defects in pigs in Australia, and one of less than five reported cases of atrial septal defects in pigs in the world. The authors conclude that there may be an element of genetic predisposition to the malformation, since it has only been reported in this inbred line of pigs.

Effects of increased inclusion of algae meal on finishing steer performance and carcass characteristics.

The deoiled residue from the production of heterotrophic microalgae can be combined with soyhulls to form a novel feedstuff called algae meal (ALG). To determine the effects of replacing corn in a finishing diet with ALG on growth, mineral status, carcass characteristics, and longissimus thoracis fatty acid profile, crossbred steers (168) were blocked by BW (432 ± 30.8 kg) into pens of 6 steers (7 pens per treatment). Pens received 1 of 4 diets: a corn-based control (CON), 14% ALG, 28% ALG (ALG28), and 42% ALG (ALG42). Corn was replaced by ALG on a DM basis. Steer BW were taken on d 0, 1, 28, 56, 74, 101, and 102, and steers were harvested on d 103. Pen was the experimental unit and DMI, ADG, and G:F data were analyzed as repeated measures. Two steers per pen were selected for sampling of blood and liver (d -1 and 96) and collection of rib steaks at harvest. There was a treatment by × time effect ( = 0.10) for overall DMI, where DMI linearly increased ( ≤ 0.008) across all time periods except Day 28 through, 56 when DMI was not different between ALG28 and ALG42. There was a treatment by time effect for ADG ( < 0.01), with ADG linearly decreasing ( ≤ 0.03) in the first and third month, not differing ( = 0.95) in the second month, and linearly increasing ( < 0.01) in the fourth month as ALG increased in the diet. Final BW and HCW did not differ ( ≥ 0.50) between CON- and ALG-fed cattle. There was a treatment × time effect for G:F ( < 0.01), with G:F linearly decreasing ( ≤ 0.01) in the first 3 mo as ALG increased in the diet, whereas G:F linearly increased ( < 0.01) in the fourth month. Based on steer performance, calculated dietary NEg linearly decreased ( < 0.01) as ALG increased in the diet. Yield grade linearly decreased ( = 0.02) and there was a tendency for dressing percent and 12th-rib back fat to linearly decrease ( ≤ 0.10) as ALG increased in the diet. Plasma Cu, Fe, and Mg concentrations were not different ( ≥ 0.31) in CON vs. ALG cattle; however, plasma Zn concentrations linearly increased ( = 0.03) as ALG increased in the diet. Total lipid, SFA, MUFA, and PUFA concentrations in the longissimus thoracis did not differ ( ≥ 0.13) between CON- and ALG-fed cattle. Interestingly, the atherogenic index linearly decreased ( < 0.01) as ALG increased in the diet. Algae meal may have a lesser energy value than corn; however, a minimal effect on carcass performance suggests ALG may serve as a potential replacement for corn in feedlot diets.

Assessment of algae meal as a ruminant feedstuff: Nutrient digestibility in sheep as a model species.

Heterotrophic microalgae combined with soyhulls forms an algae meal (ALG), which contains partially deoiled microalgae (PDM; 57% DM basis) and soyhulls (43%). Two experiments were conducted to evaluate the effects of PDM and ALG on lamb digestibility. In Exp. 1, 8 wethers (23.02 ± 0.54 kg) were used in a 4 × 4 Latin square design to determine the effect of the PDM portion of ALG on total tract nutrient digestibility. Diets included a soyhull-based control (CON; 53% soyhulls), 10% PDM from ALG, 20% PDM from ALG (PDM20), and 30% PDM from ALG. Dry matter and OM intake and fecal DM and OM output were similar ( ≥ 0.11) between CON- and ALG-fed lambs. Urine output linearly increased ( = 0.02) as PDM increased in diets. Dry matter, OM, NDF, and ADF digestibility linearly decreased ( < 0.01) as PDM increased in diets. Ether extract digestibility did not differ ( = 0.24) between CON- and PDM-fed lambs. Nitrogen digestibility and N retention linearly decreased ( ≤ 0.05) as PDM increased in the diet. In Exp. 2, to determine the effects of ALG on diet and nutrient digestibility and N retention, 10 whiteface cross wethers (33.71 ± 0.55 kg) were used in a replicated 5 × 5 Latin square. Diets included a cracked corn-based control (CORN), 15% ALG, 30% ALG, 45% ALG (ALG45), and 60% ALG (ALG60). Dry matter and OM digestibility linearly ( < 0.001) decreased as ALG inclusion increased. Digestibility of NDF and ADF were lesser ( ≤ 0.03) for CORN-fed sheep than for ALG-fed sheep and linearly ( ≤ 0.03) increased as ALG increased in the diet. Ether extract digestibility was lesser ( = 0.002) for CORN than ALG, with a linear ( = 0.002) increase as ALG inclusion increased. There was a cubic ( = 0.03) effect for N digestibility with ALG45 and ALG60 being lesser and CORN being greater than all other treatments. Retention of N and plasma urea N concentration did not differ ( ≥ 0.22) between CORN and ALG. Nonfibrous carbohydrate digestibility linearly ( < 0.001) decreased as ALG increased in the diet. These results suggest that the PDM portion of ALG may be less digestible than soyhulls in ruminants, and differences in N retention in Exp. 1 may suggest an effect on growth in lambs. Furthermore, changes in digestibility of specific nutrients suggest that ALG is more characteristic of a concentrate rather than a fibrous feedstuff. However, lambs will readily consume ALG and this novel feedstuff could potentially serve as a viable component of ruminant diets.

Evaluation of an enzyme immunoassay for total IgE on a semi-automated analyser. A multicentre study.

Total serum IgE was measured by a semi-automated enzyme immunoassay on sera from normal and disease groups. Data from this investigation was analyzed in respect of precision, linearity, sensitivity and correlation with other test methods. Using human serum pools having values between 7 and 480 IU/ml, the intra-assay coefficient of variation ranged from 3.3 to 14.6% with an arithmetic mean of 6%. The inter-assay coefficient of variation on commercially supplied control sera ranged from 4.4 to 14.2%. In addition, tests were carried out on serially diluted samples to assess the linearity of the method, and on sera with IgE levels of less than 5 IU/ml in order to assess its sensitivity. It was shown that the technique being assessed was unaffected by the presence of lipid or haemoglobin or by the addition of bilirubin or any one of 46 commonly prescribed drugs each at double its toxic dose. There was good correlation between the semi-automated enzyme immunoassay technique and four other methods used during this study. This technique exhibits excellent specificity, reproducibility and a sensitivity well within clinical demands.

The separation of human serum IgG into subclass fractions by immunoaffinity chromatography and assessment of specific antibody activity.

Murine monoclonal antibodies ( McAbs ) with specificity for subclass-specific or subclass-restricted determinants on human IgG have been coupled to Sepharose to generate affinity columns. The judicial use of positive and negative chromatography and the exploitation of the special properties of individual McAb affinity columns has allowed the preparation of individual IgG subclasses from polyclonal IgG containing less than 1% contamination by any other IgG subclass. The specificity of the antibodies present in each polyclonal IgG subclass preparation has been assayed against a bacterial toxoid (tetanus), 2 bacterial cell wall antigens (E. coli and pneumococcal) and coat antigen(s) of a DNA virus (CMV). Antibodies were predominantly IgG1 to tetanus toxoid, IgG2 to pneumovax and E. coli cell walls, and IgG1, 2 and 3 to CMV coat antigens.

The prophylactic use of low-dose amphotericin B in bone marrow transplant patients.

PURPOSE: To evaluate the efficacy of prophylactic low-dose amphotericin B (0.1 mg/kg per day) (LDA) in preventing fungal infections in patients who have had a bone marrow transplant (BMT). MATERIALS AND METHODS: Double-blind, randomized, controlled trial in which patients undergoing bone marrow transplantation received intravenous LDA or similar-appearing placebo from the onset of neutropenia until the absolute neutrophil count remained > 0.5 x 10(9)/L, or until high-dose amphotericin B was initiated. Weekly surveillance cultures were obtained from all patients. RESULTS: Five of 18 patients (28%) randomized to placebo developed documented systemic fungal infections within the first 30 days after transplantation, compared to none of 17 patients who received LDA (P = 0.045). LDA recipients received fewer days of high-dose amphotericin B (P = 0.04) and fewer days of antibiotics (P = 0.008). There were trends towards fewer days of hospitalization (P = 0.14) and improved survival (P = 0.08); these differences were statistically significant among recipients of allogeneic BMT. No adverse effects occurred with LDA therapy. CONCLUSIONS: LDA appears to be safe and to reduce early systemic fungal infections in BMT recipients. Improved survival was observed among LDA recipients, but this was not directly attributable to the prevention of fungal infection.

A simple, rapid ELISA method for the detection of DNA antibodies.

Employing an enzyme-linked immunosorbent assay (ELISA) technique the serum antibodies against native (double stranded) and denatured (single stranded) deoxyribonucleic acid (DNA) have been measured in various disease groups and a group of blood donor sera. The ELISA method has been compared with a radioimmunoassay method using native (double stranded) DNA is substrate antigen and a latex-fixation technique using particles coated with soluble deoxyribonucleoprotein (SNP). It is concluded that ELISA offers an economic and reliable alternative to isotope techniques for the assessment of antibody content in systemic lupus erythematosus (SLE) and related disease states for the clinical laboratory.

Clitoroplasty with preservation of neurovascular pedicles.

BACKGROUND: Optimal sexual function after surgical correction of clitoral hypertrophy requires an adequate postoperative innervation and vascular supply to the glans clitoris. Several clitoroplasty methods have been reported, but few describe preservation of dorsal and ventral neurovascular bundles in sexually mature women. CASE: A 22-year-old woman with clitoromegaly caused by non-salt-wasting classic 21-hydroxylase deficiency presented for a second surgical procedure after an operation in her infancy. The erect clitoral length exceeded 7.5 cm. Clitoral reduction was done through a semicircular incision in the phallus, with preservation of dorsal and ventral neurovascular pedicles. CONCLUSION: Preservation of ventral and dorsal vascular pedicles at clitoroplasty had a satisfactory result in sexually mature women.