Non-percolating small metallic clusters and sharp suppression of metallicity in RE0.55Sr0.45Mn1-xRuxO3 manganites.

The origin of the anomalous sharp phase transition from a ferromagnetic metal into a ferromagnetic insulator has been investigated in ruthenium (Ru)-doped RE0.55Sr0.45Mn1-xRuxO3 (0 ≤ x ≤ 0.25) manganites (RESRMO) with RE(A-site) = Sm, Eu and Gd. The transition is independent of RE and occurs at a Ru doping level x of around 0.16-0.18. The analysis of the temperature derivative of the resistivity and the magneto-resistance at high temperatures as a function of x suggests that the suppression of metallicity originates from the doping driven magnetic/spin disorder that coexist within the ferromagnetic metallic/insulating matrix in these compounds.

Electron beam induced tunneling magnetoresistance in spatially confined manganite bridges.

Certain manganites exhibit rich and technologically relevant transport properties which can often be attributed to the existence and changes of the intrinsic electronic phase competition within these materials. Here we demonstrate that a scanning electron beam can be used to artificially create domain configurations within La0.3Pr0.4Ca0.3MnO3 thin film microbridges that results in novel magneto-transport effects. In particular, the electron beam preferentially produces insulating regions within the narrow film and can be used to create a configuration consisting of ferromagnetic metallic domains separated by a potential barrier. This arrangement enables the spin-dependent tunneling of charge carriers and can produce large switching tunneling magnetoresistance effects which were initially absent. Hence, this work describes a new and potentially powerful method for engineering the electronic phase domains in manganites to generate functional transport properties that are important for spintronic devices.

Characterization of carbapenem-resistant Escherichia coli and Klebsiella pneumoniae from a healthcare region in Hong Kong.

Carbapenem-resistant Enterobacteriaceae represents a major public health issue. This study investigated the clonality and resistance mechanisms of 92 carbapenem-resistant E. coli (n = 21) and K. pneumoniae (n = 71) isolates collected consecutively from clinical specimens and patients at high risk of carriage between 2010 and 2012 in a healthcare region in Hong Kong. Combined disk tests (CDTs) and the Carba NP test were used for phenotypic detection of carbapenemases. PCR assays were used to detect carbapenemase genes. All isolates were intermediate or resistant to at least one carbapenem. Nine (9.8 %) isolates were genotypic carbapenemase producers and included six K. pneumoniae (one ST1306/bla IMP-4, one ST889/bla IMP-4, two ST11/bla KPC-2, one ST258/bla KPC-2, one ST483/bla NDM-1) and three E. coli (one ST131/bla IMP-4, two ST744/ bla NDM-1) isolates. All nine isolates carrying carbapenemase genes could be detected by the CDTs and the Carba NP test. PCR identified bla CTX-M and bla AmpC alone or in combination in 77.8 % (7/9) and 96.4 % (80/83) of the carbapenemase-producers and non-producers, respectively. Porin loss was detected in 22.2 % (2/9) and 59.0 % (49/83) of the carbapenemase-producers and non-producers, respectively. Overall, the E. coli clones were diverse (14 different STs), but 36.6 % (26/71) of the K. pneumoniae isolates belonged to ST11. In conclusion, the prevalence of carbapenemases among carbapenem-nonsusceptible E. coli and K. pneumoniae remained low in Hong Kong. Porin loss combined with AmpC and/or CTX-M type ESBL was the major mechanism of carbapenem resistance in the study population.

Evaluation of two chlorhexidine-alcohol-based skin disinfectants in blood donation setting.

BACKGROUND: Source reduction is important in minimizing bacterial-contaminated risk of blood products, but previous evaluation of chlorhexidine (CHX) was confounded by inability of Tween and lecithin to neutralize CHX. The study aims to address this limitation and also evaluates the effectiveness of two CHX­alcohol-based skin disinfectants in blood donation setting. METHODS: A two-stage observational study was conducted. A single step 2% chlorhexidine gluconate/70% isopropyl alcohol brush (CHX/IPA-1) was first compared with current skin disinfection procedure consisting of sequential application of 10% povidone-iodine and 70% isopropyl alcohol (PI/IPA). Standard plates with conventional neutralizers (0·3% Tween-80, 0·1% lecithin) were used to enumerate residual bacterial counts. Then, CHX/IPA-1 was compared with another applicator CHX/IPA-2 with identical disinfectant contents using in-house plates with neutralizers (3% Tween-80, 0·3% lecithin, 0·1% histidine, 0·5% sodium thiosulphate, 3% saponin, 1% ether sulphate) having enhanced ability to neutralize CHX. RESULTS: All three products were found to reduce plate counts by > 2 log10 after disinfection. The CHX/IPA-1 group gave fewer residual bacterial growth on standard plates than PI/IPA group (5·9% vs. 61·7%, P < 0·001). With the use of in-house plates, residual bacterial growth was of no difference in both CHX/IPA-1 and CHX/IPA-2 groups (42·5% vs. 49·4%, P = 0·26). CONCLUSION: Good efficacy was observed with one-stage application of CHX/IPA in predonation skin disinfection and it could replace PI/IPA. However, the efficacy of CHX/IPA could be grossly overestimated in testing with standard plates because of insufficient neutralization

Photo-induced persistent inversion of germanium in a 200-nm-deep surface region.

The controlled manipulation of the charge carrier concentration in nanometer thin layers is the basis of current semiconductor technology and of fundamental importance for device applications. Here we show that it is possible to induce a persistent inversion from n- to p-type in a 200-nm-thick surface layer of a germanium wafer by illumination with white and blue light. We induce the inversion with a half-life of ~12 hours at a temperature of 220 K which disappears above 280 K. The photo-induced inversion is absent for a sample with a 20-nm-thick gold capping layer providing a Schottky barrier at the interface. This indicates that charge accumulation at the surface is essential to explain the observed inversion. The contactless change of carrier concentration is potentially interesting for device applications in opto-electronics where the gate electrode and gate oxide could be replaced by the semiconductor surface.

Plasmid-mediated fosfomycin resistance in Escherichia coli isolated from pig.

Previous studies have reported plasmid-mediated fosA3 among Escherichia coli originating from human and companion animals. In this study, the plasmid, designated pHK23a originating from a multidrug-resistant E. coli isolate recovered from a slaughter pig in December 2008 in Hong Kong, China was sequenced. In conjugation, the plasmid readily transferred to E. coli J53 at high frequencies. It belongs to the narrow host range IncFII incompatibility group and is 73,607 bp in length. Sequence alignment showed that pHK23a has a 59.1 kb backbone which shares high homology with the prototype R100 plasmid and a 14.5 kb variable region. The variable region includes three genes mediating antimicrobial resistance (fosA3, Δbla(TEM-1), bla(CTX-M-3)), ten mobile genetic elements (four copies of IS26, insA, ΔinsB, ΔTn2, IS1, ΔISEcp1, Δintl1), the tir transfer inhibition protein, the pemI/pemK addiction system and eight ORFs of unknown functions (orf1, orf2, Δorf3, orf20, orf23, orf24, ycdA and ycdB). The three resistance genes were organized in a novel IS26-composite transposon-like structure. In conclusion, this is the first report of fosA3 containing plasmid in an isolate of pig origin. Since IncFII plasmids spread efficiently in Enterobacteriaceae, the detection of fosA3 with bla(CTX-M) is worrisome and might become a public health concern.

Dissemination of plasmid-mediated fosfomycin resistance fosA3 among multidrug-resistant Escherichia coli from livestock and other animals.

AIMS: To investigate plasmid-mediated fosfomycin resistance related to fosA3 in Escherichia coli isolates collected from different animals in Hong Kong, China, 2008-2010. METHODS AND RESULTS: In total, 2106 faecal specimens from 210 cattle, 214 pigs, 460 chickens, 398 stray cats, 368 stray dogs and 456 wild rodents were cultured. The faecal colonization rates of fosfomycin-resistant E. coli were as follows: 11.2% in pigs, 8.6% in cattle, 7.3% in chickens, 2.4% in dogs, 0.8% in cats and 1.5% in rodents. The cultures yielded 1693 isolates of which 831 were extended-spectrum ß-lactamases (ESBL) producers. Fosfomycin-resistant isolates were more likely than fosfomycin-susceptible isolates to be producers of ESBL and to have resistance to chloramphenicol, ciprofloxacin, cotrimoxazole, gentamicin and tetracycline. Of the 101 fosfomycin-resistant isolates, 97 (96.0%) isolates were fosA3 positive and 94 (93.1%) were bla(CTX) (-M) positive. PCR mapping showed that the fosA3-containing regions were flanked by IS26, both upstream and downstream in 81 (83.5%) isolates, and by an upstream bla(CTX-M-14) -containing transposon-like structure (ΔISEcp1-bla(CTX-M-14) -ΔIS903 or ISEcp1-IS10 -bla(CTX-M-14) -ΔIS903) and a downstream IS26 in 14 (14.4%) isolates. For the remaining two isolates, fosA3 was flanked by a downstream IS26 but the upstream part cannot be defined. In a random subset of 18 isolates, fosA3 was carried on transferable plasmids with sizes of 50-200 kb and the following replicons: F2:A-B- (n = 3), F16:A1:B- (n = 2), F24:A-B- (n = 1), N (n = 1), B/O (n = 1) and untypeable (n = 3). SIGNIFICANCE AND IMPACT OF THE STUDY: This study demonstrates the emergence of fosA3-mediated fosfomycin resistance among multidrug-resistant E. coli isolates from various animals. IS26 transposon-like structures might be the main vehicles for dissemination of fosA3.

Dissemination of pHK01-like incompatibility group IncFII plasmids encoding CTX-M-14 in Escherichia coli from human and animal sources.

Few studies have compared CTX-M encoding plasmids identified in different ecological sources. This study aimed to analyze and compare the molecular epidemiology of plasmids encoding CTX-M-14 among strains from humans and animals. The CTX-M-14 encoding plasmids in 160 Escherichia coli isolates from animal faecal (14 pigs, 16 chickens, 12 cats, 8 cattle, 5 dogs and 3 rodents), human faecal (45 adults and 20 children) and human urine (37 adults) sources in 2002-2010 were characterized by molecular methods. The replicon types of the CTX-M-14 encoding plasmids were IncFII (n=61), I1-Iγ (n=24), other F types (n=23), B/O (n=10), K (n=6), N (n=3), A/C (n=1), HI1 (n=1), HI2 (n=1) and nontypeable (n=30). The genetic environment, ISEcp1 -bla(CTX-M-14) - IS903 was found in 89.7% (52/58), 87.7% (57/65) and 86.5% (32/37) of the animal faecal, human faecal and human urine isolates, respectively. Subtyping of the 61 IncFII incompatibility group plasmids by replicon sequence typing, plasmid PCR-restriction fragment length polymorphism and marker genes (yac, malB, eitA/eitC and parB/A) profiles showed that 31% (18/58), 30.6% (20/65) and 37.8% (14/37) of the plasmids originating from animal faecal, human faecal and human urine isolates, respectively, were pHK01-like. These 52 pHK01-like plasmids originated from diverse human (20 faecal isolates from 2002, 2007 to 2008, 14 urinary isolates from 2004) and animal (all faecal, 1 cattle, 1 chicken, 5 pigs, 9 cats, 1 dog, 1 rodent from 2008 to 2010) sources. In conclusion, this study highlights the importance of the IncFII group, pHK01-like plasmids in the dissemination of CTX-M-14 among isolates from diverse sources.

Tuberculous biliary stricture.

Tuberculosis (TB) of the hepatobiliary system is not uncommon, but as a cause of biliary strictures, it is very rare. It poses difficulty in diagnosis and often requires surgical intervention to exclude underlying malignancy. To our knowledge, there are fewer than 20 reported cases in the English literature. We report a 35-year-old Filipino woman who presented with a 3-day history of obstructive jaundice, associated with significant weight loss and anorexia. Computed tomography (CT) revealed dilated intrahepatic biliary system secondary to distal stricture at the confluence of the left and right bile ducts. Magnetic resonance cholangiopancreatography characterised the lesion as an irregular stricturing at several sites in the common bile duct. Incidentally, the scans also showed indeterminate pulmonary nodules in the right lower lobes. CT thorax confirmed bilateral involvement of the lungs. She required percutaneous transhepatic drainage for biliary decompression. Tests on tissue from the lung lesions, the blood, and the bile all confirmed the presence of TB. She was treated with anti-TB medication. This report emphasizes the importance of considering TB as a possibile cause of biliary stricture, especially in South-East Asia.

Nature of weak magnetism in SrTiO3/LaAlO3 multilayers.

We report the observation of weak magnetism in superlattices of LaAlO(3)/SrTiO(3) using ß-detected nuclear magnetic resonance. The spin lattice relaxation rate of ^{8}Li in superlattices with a spacer layers of 8 and 6 unit cells of LaAlO(3) exhibits a strong peak near ~35 K, whereas no such peak is observed in a superlattice with spacer layer thickness of 3 unit cells. We attribute the observed temperature dependence to slowing down of weakly coupled electronic moments at the LaAlO(3)/SrTiO(3) interface. These results show that the magnetism at the interface depends strongly on the thickness of the spacer layer, and that a minimal thickness of ~4-6 unit cells is required for the appearance of magnetism. A simple model is used to determine that the observed relaxation is due to small fluctuating moments (~0.002µ(B)) in the two samples with a larger LaAlO(3) spacer thickness.

Cellular immunotherapy for high-grade glioma.

The outcome for patients with the most common primary brain tumor, glioblastoma multiforme (GBM), remains poor. Several immunotherapeutic approaches are actively being pursued including antibodies and cell-based therapies. While the blood-brain barrier protects brain tumor cells from therapeutic antibodies, immune cells have the ability to traverse the blood-brain barrier and migrate into GBM tumors to exert their therapeutic function. Results of Phase I clinical studies with vaccines to induce GBM-specific T cells are encouraging and Phase II clinical trials are in progress. Nonvaccine-based cell therapy for GBM has been actively explored over the last four decades. Here we will review past clinical experience with adoptive cell therapies for GBM and summarize current strategies on how to improve these approaches.

Extensive dissemination of CTX-M-producing Escherichia coli with multidrug resistance to 'critically important' antibiotics among food animals in Hong Kong, 2008-10.

OBJECTIVES: To assess the occurrence of faecal carriage of Escherichia coli with resistance to 'critically important' antibiotics in various animals. METHODS: Rectal or cloacal swabs were obtained weekly from cattle, pigs, chickens, cats, dogs and wild rodents over a 2 year period. Plain and antibiotic-containing medium was used for bacterial isolation. Selected isolates were characterized by molecular methods. RESULTS: In total, 2106 faecal specimens from 398 cats, 460 chickens, 368 dogs, 210 cattle, 214 pigs and 456 rodents were cultured. The faecal carriage rate of extended-spectrum ß-lactamase (ESBL)-producing E. coli was highest in pigs (63.6%, 136/214) and lowest in rodents (4.2%, 19/456). The faecal ESBL-producing E. coli carriage rate for food-producing animals (53.6%, 474/884) was significantly higher than that for cats/dogs (14.0%, 107/766; P<0.01) and wild rodents (4.2%, 19/456; P<0.01). ESBL-producing isolates from food animals often (33%-81%) had multidrug (≥4) resistance to amikacin, chloramphenicol, ciprofloxacin, co-trimoxazole, gentamicin, nalidixic acid, netilmicin, nitrofurantoin and tetracycline. Most (91.2%) of the ESBL-producing isolates had CTX-M-type enzymes. A total of 10 alleles (3, 13, 14, 15, 24, 27, 28, 55, 65 and 98) from two CTX-M families (M1 and M9) were found. PFGE showed that the CTX-M-producing isolates were genetically diverse. CONCLUSIONS: This study shows that food animals are a major reservoir of E. coli with multidrug resistance to many antibiotics that are ranked as critically important in human medicine.

Complete sequencing of the FII plasmid pHK01, encoding CTX-M-14, and molecular analysis of its variants among Escherichia coli from Hong Kong.

OBJECTIVES: We characterized plasmids encoding CTX-M-14 ß-lactamase originating from Escherichia coli isolates recovered from patients with uncomplicated cystitis or individuals with faecal colonization in Hong Kong from 2002 to 2004. METHODS: Plasmids carrying CTX-M-14 were studied by conjugation, replicon typing, S1 nuclease-PFGE and plasmid PCR-restriction fragment length polymorphism (RFLP). The complete sequence of pHK01, a 70 kb plasmid encoding CTX-M-14 from an E. coli strain, was determined and the results compared with reference plasmids and aligned with GenBank data. RESULTS: The blaCTX-M-14 plasmids could be transferred in 23 of 44 E. coli strains tested. Among the 23 transconjugants, the replicon types of the CTX-M-14-encoding plasmid were FII (n=13), I1-Iγ (n=4), F1B (n=2), FII and I1-Iγ (n=1), K (80 kb, n=1) and undetermined (n=2). Plasmid pHK01 (FII replicon) shares a high degree of homology with R100 except mainly for a 11 kb variable region containing blaCTX-M-14 (with an upstream ISEcp1 and a downstream truncated IS903), an iron transport system, an outer membrane protein (malB, maltoporin) and a putative toxin-antitoxin plasmid stability system (yacABC). It was highly related to blaCTX-M-14 (pKF3-70) and blaCTX-M-24 (pEG356) plasmids reported from mainland China in 2006 and Vietnam in 2007, respectively. Subtyping by a plasmid PCR-RFLP scheme showed that 10 of the 13 FII plasmids originating from isolates collected by multiple laboratories exhibited either identical or highly similar profiles. CONCLUSIONS: This study showed that narrow host-range FII plasmids play important roles in the dissemination of CTX-M-14. FII plasmids closely related to pHK01 have disseminated widely in the Hong Kong community.

Epidemiology and clonality of multidrug-resistant Acinetobacter baumannii from a healthcare region in Hong Kong.

We assessed the risk factors and molecular epidemiology of multidrug-resistant Acinetobacter baumannii (MDR-AB) in Hong Kong. The patients were treated in five hospitals in a healthcare region during 2005-2006. We performed genomic identification by amplified rRNA gene restriction analysis (ARDRA) and investigated the existence of metallo-beta-lactamases and the clonality of representative MDR-AB strains by phenotypic and molecular methods. Forty-five subjects with MDR-AB were compared with 135 controls (patients with no MDR-AB). In the logistic regression, chronic wound (odds ratio: 29.5, 95% confidence interval: 8.1-107.2; P<0.001) was the only factor independently associated with MDR-AB colonisation or infection. ARDRA identified all 45 MDR-AB as genomic species 2TU. Pulsed-field gel electrophoresis clustered all except two isolates into two clonal types, designated HKU1 and HKU2 with 24 and 19 isolates, respectively. The main features of HKU1 strains were ST26, adeB type XII, positivity for bla(OxA-23-like) and bla(OxA-51-like) genes and high level resistance to carbapenems. Most HKU1 strains retained susceptibility to gentamicin, cotrimoxazole and minocycline. By contrast, HKU2 strains exhibited ST22, adeB type II, and were usually positive only for the bla(OxA-51-like) gene and resistant to gentamicin, cotrimoxazole and minocycline. Both clones were found to have disseminated widely. In conclusion, clonal expansion is playing major roles in the increase of MDR-AB in these hospitals in Hong Kong. The findings highlight the need to enhance infection control measures.

Distribution of integron-associated trimethoprim-sulfamethoxazole resistance determinants among Escherichia coli from humans and food-producing animals.

AIMS: To compare the distribution of integrons and trimethoprim-sulfamethoxazole resistance genes among Escherichia coli isolates from humans and food-producing animals. METHODS AND RESULTS: A collection of 174 multidrug-resistant E. coli isolates obtained from faecal samples of food-producing animals (n = 64) and humans (n = 59), and patients with urinary tract infections (n = 51) in Hong Kong during 2002-2004 were studied. The strains were analysed for their phylogenetic groups, the presence of sul genes (sul1 and sul2), integrons (intl1 and intl2) and class 1 integron-associated dfr cassette genes by PCR, restriction enzyme analysis and sequencing. Integrons were identified in 110 (63.2%) isolates. The prevalence of integrons was significantly different according to the specimen sources (animal faecal 84.4%, human faecal 67.8% and human urinary 31.4%) and phylogenetic groups (B1 80.8%, A 77.6%, D 54.1% and B2 11.5%). Faecal isolates (both human and animal) are more likely to belong to group A and B1. In contrast, most urinary isolates were either groups B2 and D. Among dfr containing isolates, dfrA1 and dfrA12 were almost exclusively found in strains of phylogenetic groups A and B1; and were present in animal and human faecal isolates. In contrast, dfrA17 was found in both faecal and urinary isolates and comprised strains from all phylogenetic groups. The sul1 and sul2 genes were equally prevalent among the isolates irrespective of the specimen source and phylogenetic group status. Pulsed-field gel electrophoresis analysis of isolates with identical cassette genes showed that they were genetically diverse. CONCLUSIONS: More animal faecal isolates carry class 1 integrons than human faecal and human urinary isolates, and the distribution of phylogenetic groups is common across animal and human faecal isolates but different from human urinary isolates. SIGNIFICANCE AND IMPACT OF THE STUDY: Commensal isolates from food-producing animals are an important reservoir for integrons carrying antibiotic resistance genes.

RAD001 (everolimus) inhibits tumour growth in xenograft models of human hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide and highly resistant to available chemotherapies. Mammalian target of rapamycin (mTOR) functions to regulate protein translation, angiogenesis and cell cycle progression in many cancers including HCC. In the present study, subcutaneous patient-derived HCC xenografts were used to study the effects of an mTOR inhibitor, RAD001 (everolimus), on tumour growth, apoptosis and angiogenesis. We report that oral administration of RAD001 to mice bearing patient-derived HCC xenografts resulted in a dose-dependent inhibition of tumour growth. RAD001-induced growth suppression was associated with inactivation of downstream targets of mTOR, reduction in VEGF expression and microvessel density, inhibition of cell proliferation, up-regulation of p27(Kip1) and down-regulation of p21(Cip1/Waf1), Cdk-6, Cdk-2, Cdk-4, cdc-25C, cyclin B1 and c-Myc. Our data indicate that the mTOR pathway plays an important role in angiogenesis, cell cycle progression and proliferation of liver cancer cells. Our study provides a strong rationale for clinical investigation of mTOR inhibitor RAD001 in patients with HCC.

Hydrogen defect-level pinning in semiconductors: the muonium equivalent.

We have determined locations for the donor and acceptor levels of muonium in six semiconductor materials (Si, Ge, GaAs, GaP, ZnSe, and 6H-SiC) as a test of defect-level pinning for hydrogen. Within theoretical band alignments, our results indicate a common energy for the equilibrium charge-transition level Mu(+/-) to within experimental uncertainties. However, this is nearly 0.5 eV higher than the energy at which the equivalent level for hydrogen was predicted to be pinned. Corrections for zero-point energy account for only about 10% of this difference. We also report experimental results for the (negative-U) difference between donor and acceptor levels for Mu to be compared with calculated values for H impurities in the same materials.