Atomic layer deposition ultrathin film origami using focused ion beams.

Focused ion beam (FIB) micromachining is a powerful tool for maskless lithography and in recent years FIB has been explored as a tool for strain engineering. Ion beam induced deformation can be utilized as a means for folding freestanding thin films into complex 3D structures. FIB of high energy gallium (Ga+) ions induces stress by generation of dislocations and ion implantation within material layers, which create creases or folds upon mechanical relaxation enabled by motion of the material layers. One limitation on such processing is the ability to fabricate flat freestanding thin film structures. This capability is limited by the residual stresses formed during processing and fabrication of the films, which can result in initial curvature and deformation of films upon release from a sacrificial fabrication layer. This paper demonstrates folding in freestanding ultrathin films (<40 nm thin) of heterogeneous composition (metal, insulator, semiconductor, etc) with large lateral dimension structures (aspect ratio >1:1000) by ion-induced stress relaxation. The ultrathin flat structures are fabricated using atomic layer deposition on sacrificial polyimide. We have demonstrated vertical folding with 30 keV Ga+ ions in structures with lateral dimensions varying from 10 to 50 µm.

Ultrathin thermoacoustic nanobridge loudspeakers from ALD on polyimide.

The recent development of low-temperature (<200 °C) atomic layer deposition (ALD) for fabrication of freestanding nanostructures has enabled consideration of active device design based on engineered ultrathin films. This paper explores audible sound production from thermoacoustic loudspeakers fabricated from suspended tungsten nanobridges formed by ALD. Additionally, this paper develops an approach to lumped-element modeling for design of thermoacoustic nanodevices and relates the near-field plane wave model of individual transducer beams to the far-field spherical wave sound pressure that can be measured with standard experimental techniques. Arrays of suspended nanobridges with 25.8 nm thickness and sizes as small as 17 µm × 2 µm have been fabricated and demonstrated to produce audible sound using the thermoacoustic effect. The nanobridges were fabricated by ALD of 6.5 nm Al2O3 and 19.3 nm tungsten on sacrificial polyimide, with ALD performed at 130 °C and patterned by standard photolithography. The maximum observed loudspeaker sound pressure level (SPL) is 104 dB, measured at 20 kHz, 9.71 W input power, and 1 cm measurement distance, providing a loudspeaker sensitivity value of ∼64.6 dB SPL/1 mW. Sound production efficiency was measured to vary proportional to frequency f 3 and was directly proportional to input power. The devices in this paper demonstrate industrially feasible nanofabrication of thermoacoustic transducers and a sound production mechanism pertinent to submicron-scale device engineering.

Preoperative C-reactive protein predicts the severity and likelihood of complications following appendicectomy.

INTRODUCTION: Diagnostic laparoscopy with appendicectomy (LA) has become the accepted method of investigation and treatment of appendicitis. However, concerns remain in cases of complicated appendicitis when many advocate conversion to an open procedure (LCOA) owing to the risk of complications. The aim of this study was to look for factors that could predict complications occurring in patients undergoing appendicectomy. METHODS: Data inclusive of all consecutive appendicectomies over a two-year period were retrieved from the computerised theatre database. Clinical details including admission inflammatory markers, complications, severity (final pathology) and length of stay were collected from the discharge letter. Readmissions were identified as those hospital identifiers had a second set of admission dates and/or a second discharge letter. RESULTS: During the 2-year study period, 517 appendicectomies were performed. Of these, 429 patients (83%) had LA and the remaining 88 (17%) had LCOA. The LA group had a mean age of 28 years (range: 2-86 years) and a mean C-reactive protein (CRP) level of 71 mg/l (range: 0-480 mg/l) while the LCOA group had a mean age of 46 years (range: 11-92 years) and a mean CRP level of 162 mg/l (range: 3-404 mg/l). These differences in age and CRP were significant (p<0.001). LA patients were less likely to have complications overall (22% vs 52%, p=0.015). Complications were independently more than twice as common with established inflammation with a CRP level of >150 mg/l (p<0.05). CONCLUSIONS: A high preoperative CRP level predicts an increased rate of postoperative complication due to established inflammation and/or infection. This raises the question of whether we should be offering primary open appendicectomies to patients with a CRP level of >150 mg/l.

Laparoscopic adjustable gastric band survival in a high-volume bariatric unit.

BACKGROUND: Although laparoscopic adjustable gastric bands (LAGBs) have been shown to be efficacious, their long-term usefulness has been questioned. This study examined the fate of LAGBs in a unit with over a decade of experience in their use. Patient factors related to the need for, and timing of, band removal were investigated. METHODS: A prospectively maintained database was used to identify all patients with a LAGB. Patient demographics, need for band removal and band survival were examined. Logistic regression modelling was done and Kaplan-Meier curves were calculated for band survival. RESULTS: Between 2000 and 2012, 674 bands were placed in 665 patients. Of these, 143 (21.2 per cent) were removed. There was no difference in rates of removal by sex (P = 0.910). The highest rates of removal were in patients aged less than 40 years (26.7 per cent), and those with a BMI greater than 60 kg/m2 (28.6 per cent). Earlier band removal was seen in younger patients (P = 0.002). Rates of removal increased linearly by earlier year of placement. Of bands placed 4 or more years previously, 35.0 per cent required removal. Eighty-three patients (58.0 per cent) who had a LAGB removed went on to have a further bariatric procedure (band to bypass, 66; band to sleeve, 17). CONCLUSION: Even in experienced hands LAGB does not appear to be a definitive solution. In a large number of patients there appears to be a finite 'band life', with the majority of patients requiring conversion to a further bariatric procedure.

Artemisia annua extracts, artemisinin and 1,8-cineole, prevent fruit infestation by a major, cosmopolitan pest of apples.

CONTEXT: Extracts of Artemisia annua (L.) (Asteraceae) and artemisinins are used for treatment of malaria, parasitic infections and have potent anticancer properties in cell lines. Eucalyptus oil and 1,8-cineole have antimicrobial, immune-stimulatory, anti-inflammatory, antioxidant, analgesic, and spasmolytic effects. Codling moth, Cydia pomonella, (L.) (Tortricidae), is a major cosmopolitan pest of the apple, potentially causing damage translating to 40 billion US dollars per year, globally. Currently used control measures are either hazardous to agricultural workers and harmful to environment, or ineffective. The potential of plant-derived semiochemicals for codling moth control is heavily understudied. OBJECTIVE: This study evaluated the potential of A. annua extracts, and two chemicals that this plant contains, artemisinin and 1,8-cineole, for preventing apple feeding and infestation by neonate Cydia pomonella larvae. METHODS: We studied effects of A. annua extracts, artemisinin and 1,8-cineole on apple infestation by neonate codling moth larvae using fruit choice assay in laboratory experiments. Preference of fruit treated with test solutions versus fruit treated with solvent was recorded and analyzed. RESULTS: Crude A. annua extracts prevented fruit feeding at 1, 3, and 10 mg/ml. Artemisinin had feeding deterrent effects at 10 and 30 mg/ml, and 1,8-cineole at 100 and 300 mg/ml. DISCUSSION AND CONCLUSIONS: A. annua contains chemicals that prevent apple infestation by codling moth neonates. Artemisinin and 1,8-cineole are among them, but there are other, polar constituents of A. annua, which have similar effects. There is a potential of using our findings in codling moth control and production of codling moth-resistant apples.

Major histocompatibility complex diversity in the endangered Ethiopian wolf (Canis simensis).

The major histocompatibility complex (MHC) influences immune response to infection and vaccination. In most species, MHC genes are highly polymorphic, but few wild canid populations have been investigated. In Ethiopian wolves, we identified four DLA (dog leucocyte antigen)-DRB1, two DLA-DQA1 and five DQB1 alleles. Ethiopian wolves, the world's rarest canids with fewer than 500 animals worldwide, are further endangered and threatened by rabies. Major rabies outbreaks in the Bale Mountains of southern Ethiopia (where over half of the Ethiopian wolf population is located) have killed over 75% of wolves in the affected sub-populations. In 2004, following a rabies outbreak, 77 wolves were vaccinated, and 19 were subsequently recaptured to monitor the effectiveness of the intervention. Pre- and post-vaccination rabies antibody titres were available for 18 animals, and all of the animals sero-converted after vaccination. We compared the haplotype frequencies of this group of 18 with the post-vaccination antibody titre, and showed that one haplotype was associated with a lower response (uncorrected P < 0.03). In general, Ethiopian wolves probably have an adequate amount of MHC variation to ensure the survival of the species. However, we sampled only the largest Ethiopian wolf population in Bale, and did not take the smaller populations further north into consideration.

Association of HLA-DRB1* and keloid disease in an Afro-Caribbean population.

BACKGROUND: Keloid disease (KD) is a fibroproliferative dermal tumour of unknown aetiology. The high incidence of familial clustering in KD, its prevalence in certain races and its concordance in identical twins suggest a strong genetic predisposition to keloid formation. The highest incidence of keloids is found in black populations, where the incidence has been estimated to be up to 16%. The most polymorphic genetic system in vertebrates is the major histocompatibility complex (MHC) also known as the human leucocyte antigen (HLA) system. The MHC has been shown to be strongly associated with numerous conditions. Of particular relevance is the association of DR2 with dermal fibrotic diseases including sarcoidosis and systemic sclerosis. AIMS: To investigate the aetiology of KD and the potential involvement of the MHC. METHODS: We compared the HLA-DRB1 phenotype frequencies of Afro-Caribbean patients of Jamaican origin with keloid scars against those seen in a control population of the same ethnicity (n = 121; mean age 34.8 years, range 14-88). In total, 180 keloid cases of Afro-Caribbean origin, recruited from Kingston, Jamaica, were evaluated in the study (mean age 29.7 years, range 2-90 years). HLA-DRB1 alleles were determined in all participants using a semiautomated typing system of reverse hybridization PCR with sequence-specific oligonucleotide probes. HLA-DRB1* phenotype frequencies were established in the Jamaican Afro-Caribbean population and comparisons made between cases and controls. Furthermore, the influence of multiple vs. single lesions, patient gender and family history were also investigated. RESULTS: Differences were observed between the disease and control cohorts although none was significant. CONCLUSIONS: This study does not support an association between HLA-DRB1* alleles and susceptibility to keloid in people of Afro-Caribbean origin.

Genetic susceptibility to raised dermal scarring.

Raised skin scars, such as keloid and hypertrophic scars mostly occur post-wounding in the human dermis. There is compelling evidence for a genetic component to these conditions, given the familial predisposition, varied incidence in different ethnic populations and the presence in twins. The aim of this study was to perform a systematic review of the literature regarding genetic susceptibility to raised dermal scarring. We identified relevant articles by a systematic search of relevant search engines. Key search terms included: keloid disease, hypertrophic scarring, fibrosis, linkage analysis, gene expression, human leucocyte antigen system (HLA), twins, families, case-control association study and congenital syndromes. Numerous candidate genes have been identified, along with potential linkage regions on different chromosomes. Recent data also suggest that carriers of specific major histocompatibility complex (MHC) alleles, in particular HLA-DRB1*15, HLA-DQA1*0104, DQB1*0501 and DQB1*0503, are at increased risk of developing keloid scarring. In addition, distinct immunophenotypical profiles can distinguish between keloid and hypertrophic scars. Keloid and hypertrophic scars are multifaceted aberrations of the healing process with as yet incompletely understood aetiologies. Current data suggest a genetic susceptibility with a strong immunogenic component to dermal fibrosis with MHC genes being implicated. It appears unlikely that a single gene is responsible for the development of raised dermal scars. A likely scenario may involve the interaction of several gene pathways in addition to environmental factors. The ability to assess accurately an individual's potential genetic susceptibility to raised scarring may lead to a more personalized approach to their management in the future.

Safety and efficacy of intravenous zoledronic acid in paediatric osteoporosis.

AIM: To study the safety and efficacy of zoledronic acid treatment in children with osteoporotic bone disorders. STUDY DESIGN: Observational study in 22 patients with osteogenesis imperfecta and related conditions who were treated at our institution with zoledronic acid. These patients had initial treatment with pamidronate. Lumbar spine z-scores, annual change in areal bone mineral density, bone mineral adjusted density, fracture number and linear growth before and after zoledronic acid treatment was commenced were compared. RESULTS: Patients were treated for a mean of 3.4 years with zoledronic acid after a mean of 3.75 years of pamidronate therapy. There was no difference in areal bone mineral density accrual in the first year of zoledronic acid treatment compared to the preceding year of pamidronate treatment. Lumbar spine z-scores and bone mineral adjusted density continued to increase with zoledronic acid. Number of fractures during treatment was significantly reduced compared to baseline with either bisphosphonate, with no difference between treatments. Linear growth was not affected. CONCLUSIONS: Zoledronic acid is at least as effective as pamidronate as treatment for paediatric osteoporosis, and has a similar safety profile.

Appendicitis in pregnancy: an ongoing diagnostic dilemma.

INTRODUCTION: Appendicitis in pregnancy (AIP) is the most common nonobstetric cause of an acute abdomen requiring surgical intervention. Diagnostic difficulties arising from gestational symptoms compound the risk of foetal loss after negative appendicectomy and exponentially increase the risk to mother and foetus with delay in genuine cases. In this article, we investigate the symptoms and signs of AIP and attempt to identify consistent clinical features and review the role of imaging in diagnosis. METHOD: MEDLINE and PubMed were searched for case-control studies recording preoperative symptoms/signs suggestive of AIP, as well as appendiceal pathology. Combined likelihood and odds ratios (OR) were created for clinical features across homogenous papers. Papers examining the use of laparoscopy, ultrasound (US), computerized tomography (CT) and magnetic resonance imaging (MRI) were assessed qualitatively. RESULTS: Seven papers met the inclusion criteria for the analysis of consistent clinical features (450 patients). The only symptoms or signs significantly associated with a diagnosis of appendicitis were nausea (OR: 2.21, 95%CI: 1.34-3.66), vomiting (OR: 0.82-15.6 range) and peritonism (OR: 1.80, 95%CI: 1.06-3.04). US, CT and MRI have all been used to successfully diagnose AIP. Laparoscopic appendicectomy has been safely undertaken in pregnancy. CONCLUSION: Appendicitis will continue to challenge the diagnostic acumen of surgeons. Whilst useful, consensus regarding the safety of laparoscopy, CT and MRI in pregnancy is yet to be achieved.

Positive association of HLA-DRB1*15 with keloid disease in Caucasians.

Keloid disease (KD) is a fibroproliferative dermal tumour of unknown aetiology. The increased familial clustering in KD, its increased prevalence in certain races and concordance in identical twins suggest a strong genetic predisposition to keloid formation. The most polymorphic genetic system in all vertebrates is the major histocompatibility complex (MHC) also known as the human leucocyte antigens (HLA) system. The MHC has been shown to be strongly associated with numerous conditions. Of particular interest is the association of DR2 with dermal fibrotic diseases such as sarcoidosis. To investigate the aetiology of KD, we compared the HLA-DRB1 phenotype frequencies of Caucasoid patients with keloid scars against those observed in a control population (n = 537). A total number of 67 keloid cases were evaluated in the study. HLA-DRB1 alleles were determined in all cases and controls using a commercially available semiautomated reverse hybridization polymerase chain reaction sequence-specific oligonucleotide probes typing system. HLA-DRB1*15 phenotype frequency was higher in KD-positive Caucasians (38.8%) when compared with controls (20.9%) (corrected P = 0.017). We conclude that in Caucasians of Northern European origin, HLA-DRB1*15 is associated with risk of developing KD following injury. We have demonstrated for the first time that a genetic association exists between HLA-DRB1*15 status and the risk of developing keloid scarring in Caucasians. Our data suggest the possible involvement of an immunogenic component to KD although the exact mechanisms involved in MHC-driven abnormal fibrosis will require further investigation.

Positive association of HLA-DRB1*15 with Dupuytren's disease in Caucasians.

Dupuytren's disease (DD) is a permanent nodular condition affecting the palms and digits of the hands, leading to progressive shortening and contractures of the digits often resulting in diminished function and severe deformity. DD is thought to be one of the most common hereditary connective tissue disorders in Caucasians. To elucidate further the aetiology of DD, we compared the HLA-DRB1 phenotype frequencies of DD patients (n=67) against the HLA-DRB1 phenotype frequencies observed in a control population (n=537). HLA-DRB1*15 phenotype frequency was higher in DD positive Caucasoids (37.3%) when compared with control data (20.9%) (corrected P=0.029): we conclude that in Caucasoids of European origin, HLA-DRB1*15 is associated with risk of developing DD.

Bisphosphonate-associated osteonecrosis of the jaw: does it occur in children?

BACKGROUND: Bisphosphonate use in adult patients has been linked to osteonecrosis of the jaw (ONJ). This complication has not been systematically assessed in a paediatric population receiving bisphosphonates. OBJECTIVE: To assess our cohort of paediatric patients treated with intravenous bisphosphonate for occurrence of ONJ. DESIGN: Observational study at a tertiary children's hospital. PATIENTS: A total of 42 paediatric patients with osteoporosis who received bisphosphonate infusions for a mean of 6.5 years (SD 2.7 years) were assessed clinically and radiographically for possible ONJ. Among 42, 37 patients had received disodium pamidronate 1 mg/kg/dose at a mean cumulative dose of 19.8 mg/kg and zoledronic acid (ZA) 0.05 mg/kg/dose at a mean cumulative dose of 0.49 mg/kg; four had received ZA and one received pamidronate alone. Invasive dental treatment during bisphosphonate treatment, a known risk factor for osteonecrosis, was specifically assessed. RESULTS: In all patients assessed, including 11 who had invasive dental treatment, there were no cases of osteonecrosis. CONCLUSION: ONJ has so far not been demonstrated in this patient group.

Major histocompatibility complex typing of dogs from Russia shows further dog leukocyte antigen diversity.

Blood samples from 85 Russian dogs and wolves were collected as dried blood spots on paper and transported to the UK by mail. We obtained partial or complete three-locus canine major histocompatibility complex [dog leukocyte antigen (DLA)] class II haplotypes on 81 of these samples. Six new alleles were identified: three DLA-DRB1 and three DLA-DQB1. These alleles occurred in haplotypic combinations not previously seen in other European dogs. One haplotype appeared to lack a DQB1 allele. Two of the new haplotypes segregated through a family of dogs that was investigated.

Magnetic resonance imaging of the gallbladder: spectrum of abnormalities.

Various pathologies involving the gallbladder can manifest clinically, producing nonspecific clinical symptoms and making diagnosis difficult and challenging. Real-time sonography is the most widely used diagnostic study for the gallbladder and the primary screening examination of choice. With increasing use of magnetic resonance imaging (MRI) and MR cholangiopancreatography (MRCP), gallbladder pathology is frequently seen. Understanding the basic patterns of various disease manifestations and appearance on MRI is the key to making an accurate diagnosis. Given its inherent tissue contrast and contrast sensitivity, MRI in conjunction with MRCP can be a very valuable test in evaluating gallbladder pathology. Gallbladder pathology can be classified into congenital (such as absence), inflammatory (acute, hemorrhagic, and chronic cholecystitis), traumatic, benign (polyps) and malignant tumors (gallbladder carcinoma and lymphoma), and other disease processes can be seen in cholelithiasis, cholesterosis, thickened gallbladder wall, and Mirrizzi syndrome.

Canine DLA diversity: 1. New alleles and haplotypes.

The aim of this component was to establish the range of DLA diversity in as many dog breeds as possible. In particular, we wanted to collect breeds that had not previously been studied. Data were submitted of 937 dogs of over 80 different breeds, and these included 17 'new' breeds. Twenty-eight new alleles were identified including 21 DLA-DRB1, 2 DLA-DQA1 and 5 DLA-DQB1 alleles. These occurred in many new haplotype combinations. One haplotype was identified that appeared to lack DQB1. Two other haplotypes carry two DQB1 genes. It was clear that each dog breed has a restricted range of DLA alleles and haplotypes, and no breed had all 88 haplotypes identified in this study.

Canine DLA diversity: 2. Family studies.

The canine Major Histocompatibility Complex is referred to as DLA (for dog leukocyte antigen). There are no published studies on DLA segregation in the dog, so this part of the DLA workshop aimed to collect DNA from multigeneration families of different breeds of dogs. Twenty-two families of dogs were submitted to the workshop, comprising 313 individuals, of which 247 had one or both parents available.

Canine DLA diversity: 3. Disease studies.

There are many millions of dogs worldwide, and these dogs have many different functions. The most obvious use is providing companionship, but there are also many working dogs, including guide dogs for the blind, hearing dogs, guard dogs and farm dogs, to mention a few. The health and welfare of these dogs is of great concern to dog owners, dog breeders and to those who use dogs in their work. Dogs spontaneously develop many diseases that are very similar to their human counterparts. Dogs may, therefore, provide exceptional animal models for such diseases. Identifying genetic markers in the dog may be easier than in humans, and may then provide useful information about genes that can be transferred to humans. This study looked for associations between DLA and two autoimmune diseases of the dog, diabetes and hypothyroidism. DLA associations were found for both of these diseases.