Bolometer operating at the threshold for circuit quantum electrodynamics.

Radiation sensors based on the heating effect of absorbed radiation are typically simple to operate and flexible in terms of input frequency, so they are widely used in gas detection1, security2, terahertz imaging3, astrophysical observations4 and medical applications5. Several important applications are currently emerging from quantum technology and especially from electrical circuits that behave quantum mechanically, that is, circuit quantum electrodynamics6. This field has given rise to single-photon microwave detectors7-9 and a quantum computer that is superior to classical supercomputers for certain tasks10. Thermal sensors hold potential for enhancing such devices because they do not add quantum noise and they are smaller, simpler and consume about six orders of magnitude less power than the frequently used travelling-wave parametric amplifiers11. However, despite great progress in the speed12 and noise levels13 of thermal sensors, no bolometer has previously met the threshold for circuit quantum electrodynamics, which lies at a time constant of a few hundred nanoseconds and a simultaneous energy resolution of the order of 10h gigahertz (where h is the Planck constant). Here we experimentally demonstrate a bolometer that operates at this threshold, with a noise-equivalent power of 30 zeptowatts per square-root hertz, comparable to the lowest value reported so far13, at a thermal time constant two orders of magnitude shorter, at 500 nanoseconds. Both of these values are measured directly on the same device, giving an accurate estimation of 30h gigahertz for the calorimetric energy resolution. These improvements stem from the use of a graphene monolayer with extremely low specific heat14 as the active material. The minimum observed time constant of 200 nanoseconds is well below the dephasing times of roughly 100 microseconds reported for superconducting qubits15 and matches the timescales of currently used readout schemes16,17, thus enabling circuit quantum electrodynamics applications for bolometers.

Operation of a silicon quantum processor unit cell above one kelvin.

Quantum computers are expected to outperform conventional computers in several important applications, from molecular simulation to search algorithms, once they can be scaled up to large numbers-typically millions-of quantum bits (qubits)1-3. For most solid-state qubit technologies-for example, those using superconducting circuits or semiconductor spins-scaling poses a considerable challenge because every additional qubit increases the heat generated, whereas the cooling power of dilution refrigerators is severely limited at their operating temperature (less than 100 millikelvin)4-6. Here we demonstrate the operation of a scalable silicon quantum processor unit cell comprising two qubits confined to quantum dots at about 1.5 kelvin. We achieve this by isolating the quantum dots from the electron reservoir, and then initializing and reading the qubits solely via tunnelling of electrons between the two quantum dots7-9. We coherently control the qubits using electrically driven spin resonance10,11 in isotopically enriched silicon12 28Si, attaining single-qubit gate fidelities of 98.6 per cent and a coherence time of 2 microseconds during 'hot' operation, comparable to those of spin qubits in natural silicon at millikelvin temperatures13-16. Furthermore, we show that the unit cell can be operated at magnetic fields as low as 0.1 tesla, corresponding to a qubit control frequency of 3.5 gigahertz, where the qubit energy is well below the thermal energy. The unit cell constitutes the core building block of a full-scale silicon quantum computer and satisfies layout constraints required by error-correction architectures8,17. Our work indicates that a spin-based quantum computer could be operated at increased temperatures in a simple pumped 4He system (which provides cooling power orders of magnitude higher than that of dilution refrigerators), thus potentially enabling the integration of classical control electronics with the qubit array18,19.

Fidelity benchmarks for two-qubit gates in silicon.

Universal quantum computation will require qubit technology based on a scalable platform1, together with quantum error correction protocols that place strict limits on the maximum infidelities for one- and two-qubit gate operations2,3. Although various qubit systems have shown high fidelities at the one-qubit level4-10, the only solid-state qubits manufactured using standard lithographic techniques that have demonstrated two-qubit fidelities near the fault-tolerance threshold6 have been in superconductor systems. Silicon-based quantum dot qubits are also amenable to large-scale fabrication and can achieve high single-qubit gate fidelities (exceeding 99.9 per cent) using isotopically enriched silicon11,12. Two-qubit gates have now been demonstrated in a number of systems13-15, but as yet an accurate assessment of their fidelities using Clifford-based randomized benchmarking, which uses sequences of randomly chosen gates to measure the error, has not been achieved. Here, for qubits encoded on the electron spin states of gate-defined quantum dots, we demonstrate Bell state tomography with fidelities ranging from 80 to 89 per cent, and two-qubit randomized benchmarking with an average Clifford gate fidelity of 94.7 per cent and an average controlled-rotation fidelity of 98 per cent. These fidelities are found to be limited by the relatively long gate times used here compared with the decoherence times of the qubits. Silicon qubit designs employing fast gate operations with high Rabi frequencies16,17, together with advanced pulsing techniques18, should therefore enable much higher fidelities in the near future.

A clinical prediction score using age at diagnosis and saline infusion test parameters can predict aldosterone-producing adenoma from idiopathic adrenal hyperplasia.

PURPOSE: Accurate subtyping of the primary aldosteronism into aldosterone-producing adenoma (APA) and idiopathic adrenal hyperplasia (IAH) is important to direct for specific treatment modalities. The objective of the study was to compare the clinical and biochemical parameters of APA and IAH patients to derive a Clinical Prediction Score reliably predicting APA from IAH. METHODS: This was a retrospective multi-centre study recruiting 38 APA patients and 42 IAH patients from four major hospitals in Hong Kong using database from Surgical Outcomes Monitoring and Improvement Programme and Clinical Data Analysis and Reporting System. Their clinical and biochemical parameters were evaluated. RESULTS: Patients in APA group were younger than IAH group (mean age 48.6 ± 9.2 vs. 57.1 ± 7.3 years old, p < 0.001), had more suppressed renin before saline infusion in saline infusion test (SIT) (median 0.19 [IQR 0.15-0.37] vs. 0.39 [IQR 0.19-0.69] ng/mL/h, p = 0.01), and higher aldosterone level after saline infusion in SIT (median 674 [IQR 498-1000] vs. 327 [IQR 242-483] pmol/L, p < 0.001). A clinical prediction score using three parameters was devised, comprising age at diagnosis < 50 years, PRA before saline infusion in SIT ≤ 0.26 ng/mL/h, and aldosterone level after saline infusion in SIT ≥ 424 pmol/L. A score of 2 would predict APA with a sensitivity of 84.2% and specificity of 88.1%, and a score of 3 would predict APA with a sensitivity of 31.6% and specificity of 100%. CONCLUSIONS: Clinical Prediction Score based on the combination of age at diagnosis, PRA, and aldosterone level in the saline infusion tests could reliably predict APA from IAH.

Ancestral whole-genome duplication in the marine chelicerate horseshoe crabs.

This corrects the article DOI: 10.1038/hdy.2015.89.

Ancestral whole-genome duplication in the marine chelicerate horseshoe crabs.

Whole-genome duplication (WGD) results in new genomic resources that can be exploited by evolution for rewiring genetic regulatory networks in organisms. In metazoans, WGD occurred before the last common ancestor of vertebrates, and has been postulated as a major evolutionary force that contributed to their speciation and diversification of morphological structures. Here, we have sequenced genomes from three of the four extant species of horseshoe crabs-Carcinoscorpius rotundicauda, Limulus polyphemus and Tachypleus tridentatus. Phylogenetic and sequence analyses of their Hox and other homeobox genes, which encode crucial transcription factors and have been used as indicators of WGD in animals, strongly suggests that WGD happened before the last common ancestor of these marine chelicerates >135 million years ago. Signatures of subfunctionalisation of paralogues of Hox genes are revealed in the appendages of two species of horseshoe crabs. Further, residual homeobox pseudogenes are observed in the three lineages. The existence of WGD in the horseshoe crabs, noted for relative morphological stasis over geological time, suggests that genomic diversity need not always be reflected phenotypically, in contrast to the suggested situation in vertebrates. This study provides evidence of ancient WGD in the ecdysozoan lineage, and reveals new opportunities for studying genomic and regulatory evolution after WGD in the Metazoa.

Compound heterozygous mutations in TTC7A cause familial multiple intestinal atresias and severe combined immunodeficiency.

Familial multiple intestinal atresias is an autosomal recessive disease with or without combined immunodeficiency. In the last year, several reports have described mutations in the gene TTC7A as causal to the disease in different populations. However, exact correlation between different genotypes and various phenotypes are not clear. In this study, we report identification of novel compound heterozygous mutations in TTC7A gene in a Malay girl with familial multiple intestinal atresias and severe combined immunodeficiency (MIA-SCID) by whole exome sequencing. We found two mutations in TTC7A: one that destroyed a putative splicing acceptor at the junction of intron 17/exon 18 and one that introduced a stop codon that would truncate the last two amino acids of the encoded protein. Reviewing the recent reports on TTC7A mutations reveals correlation between the position and nature of the mutations with patient survival and clinical manifestations. Examination of public databases also suggests carrier status for healthy individuals, making a case for population screening on this gene, especially in populations with suspected frequent founder mutations.

Reconstructive surgery for females with congenital adrenal hyperplasia due to 21-hydroxylase deficiency: a review from the Prince of Wales Hospital.

OBJECTIVES: To present the results of feminising genitoplasty done in female patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. DESIGN: Case series. SETTING: A tertiary referral centre in Hong Kong. PATIENTS: Female patients with congenital adrenal hyperplasia undergoing corrective surgery for virilisation between 1993 and 2012. MAIN OUTCOME MEASURES: The operative result was judged with a scoring system (1-3) for four areas: appearance of clitoris, labia and vagina, plus requirement for revision surgery. RESULTS: A total of 23 female patients with congenital adrenal hyperplasia with a median age of 17.5 (range, 1.5-33.8) years were identified. Of these individuals, 17 presented in the neonatal period and early infancy, of which four had an additional salt-losing crisis. Six patients-including four migrants from mainland China-were late presenters at a median age of 2 (range, 0.5-14) years. Twenty-two patients had corrective surgery at a median age of 2 (range, 1-14) years. Clitoral reduction was performed in all, and further surgery in 21 patients. The additional surgery was flap vaginoplasty in 10 patients, a modified Passerini procedure in six, and a labial reconstruction in five; one patient with prominent clitoris was for observation only. Minor revision surgery (eg mucosal trimming) was required in three patients; a revision vaginoplasty was done in one individual. Of the 23 patients, 18 (78%) with a median age of 20 (range, 9.3-33.8) years participated in the outcome evaluation: a 'good' outcome (4 points) was seen in 12 patients and a 'satisfactory' (5-9 points) result in five patients. CONCLUSIONS: Nearly three quarters of our cohort (n=17) presented with classic virilising form of 21-hydroxylase deficiency. Only four (25%) patients experienced a salt-losing crisis. Female gender assignment at birth was maintained for all individuals in this group. 'Good' and 'satisfactory' outcomes of surgery were reported in nearly all participants.

Positive influence of L-carnitine on the different muscle fibres types of racing pigeons.

Succinate dehydrogenase (SDH), Ca(2+) ATPase, Lactate dehydrogenase (LDH), are involved in energy metabolism. These enzymes can be used as indicators of the energy capacity of aerobic cells. The study investigated the effects of L-carnitine supplementation on M. pectoralis superficialis, M. pectoralis profundus, M. extensor carpi radialis muscle and M. flexor carpi ulnaris. Twenty-eight racing pigeons hatched at the same time were divided randomly into three groups. Eight pigeons, which were used as the control group, were sacrificed at 92-day old. The remaining twenty pigeons continued training until they reached 157-day old, with half the pigeons getting 25 mg/head/day of L-carnitine, while the other half given the same amount of water. The pigeons were assessed by histochemical methods and reverse transcription polymerase chain reaction (RT-PCR). To assess influence of L-carnitine on muscle fibre composition and the performance of three genes' mRNA, this study applied SDH localization, SDH, Ca(2+) ATPase and LDH mRNA expression to examine the results after oral administration of L-carnitine in vivo in racing pigeons. The results showed that L-carnitine significantly elevated the amount of white muscle fibre type IIa (p < 0.05). The mRNA expression quantities of SDH and LDH gene was higher via RT-PCR method. However, the expression of Ca(2+) ATPase remains similar. In conclusion, appropriate oral administration of L-carnitine of 25 mg/pigeon/day will result in an improvement of muscles related to flying.

Reliability of acute illness dihydrorhodamine-123 testing for chronic granulomatous disease.

BACKGROUND: Dihydrorhodamine (DHR) flow cytometric analysis is used to evaluate granulocyte oxidative bursts and is the test of choice for the diagnosis of chronic granulomatous disease (CGD). We present the clinical and DHR test profiles of five subjects assessed during and after acute illness. METHODS: This was a retrospective report of the findings of five out of a total of one hundred and seventeen patients, whose blood was sent to the laboratory for dihydrorhodamine-123 flow cytometry testing between January 2005 and December 2010. Using whole blood technique and stimulation using phorbol myristate acetate, the results of DHR were expressed as stimulation index and coefficient of variation of histograms of stimulated cells and compared with healthy controls. DHR tests were repeated when the patients had recovered and were clinically well. RESULTS: These five patients showed abnormal DHR test results during their acute illness, with a stimulation index (SI) lower (p = 0.009) and coefficient of variation (CV) higher (p = 0.009) than controls. The DHR profiles repeated when patients had recovered showed normalization of tests with no significant difference for SI (p = 0.602) and CV (p = 0.917) compared to controls. Wilcoxon Signed Rank tests showed a significant improvement in SI (p = 0.043) and CV (p = 0.043) upon recovery. On follow up, all five patients were well, with no further severe or atypical infections. CONCLUSIONS: DHR may be transiently abnormal during acute illness, and may therefore not be reliable when assessed during an acute illness. If these subjects had CGD, it would be of a hypomorphic variant that has not previously been described.

Prevalence of abnormal Papanicolaou smears in female sex workers in Hong Kong.

OBJECTIVE. To investigate the prevalence of pre-cancerous uterine cervix lesions as detected in Papanicolaou (Pap) smears from female sex workers in Hong Kong. DESIGN. Retrospective analysis of laboratory records. SETTING. Private anatomical pathology laboratory, Hong Kong. PATIENTS. Female sex workers undergoing Pap smear examinations at two non-governmental organisations between 2006 and 2012. MAIN OUTCOME MEASURES. Detection of pre-cancerous uterine cervical conditions and their management. RESULTS. A total of 2697 satisfactory Pap smears from female sex workers were performed during the study period from 2006 to 2012. In these subjects, the point prevalence of low-grade squamous intraepithelial lesion and atypical squamous cells of unknown significance was 10.12% (compared with 3.92% for the general population during the same period), whereas that of high-grade squamous intraepithelial lesions and atypical squamous cells of unknown significance with or without high-grade intraepithelial lesions was 2.22% (compared with 0.54% in the general population). For both categories of lesions, the higher prevalence among female sex workers than in the general population was statistically significant. Most patients who had abnormal Pap smears received proper referrals and follow-up management according to recommended guidelines. CONCLUSIONS. Female sex workers in Hong Kong as a group had a significantly higher prevalence of abnormal Pap smears than the general population. Non-governmental organisations providing free-of-charge screening services to these women helped early detection and proper follow-up for those who had abnormal Pap smears, whilst also increasing their awareness of women's health issues.

Clinicopathological study of renal biopsies after liver transplantation.

OBJECTIVE: To perform a clinicopathological study of patients having renal biopsies after liver transplantation. DESIGN: Case series. SETTING; Queen Mary Hospital, Hong Kong. PATIENTS: All post-liver transplantation patients who had a renal biopsy in the period from January 2000 to December 2010. RESULTS: Eleven renal biopsies were retrieved for review from 10 patients with liver transplantation. The male-to-female ratio was 9:1 (age range, 47-63 years). The median liver transplant-to-renal biopsy interval was 1590 (range, 102-3699) days. The predominant histological changes were interstitial fibrosis and tubular atrophy. Diabetic nephropathy (n=6) and immunoglobulin A nephropathy (n=4) were the commonest glomerulopathies. Only one patient had chronic calcineurin inhibitor nephrotoxicity. With a mean follow-up of 53 months, three patients died 2 to 53 months post-renal biopsy. All surviving patients had chronic renal impairment. Five patients developed end-stage renal failure and four had significant persistent proteinuria. CONCLUSION: Renal pathology was variable after liver transplantation; most biopsies showed complex renal lesions, whilst calcineurin inhibitor nephrotoxicity was rare. The recognition of kidney histology attributable to metabolic derangements after liver transplantation is potentially important in the interpretation of renal biopsy specimens and patient management. The renal outlook of this group of patients is guarded.

Hitching the gallbladder in laparoscopic-assisted cholecysto-cholangiography: a simple technique.

Neonatal cholestatic disorder in the late neonatal period requires often cholangiography to differentiate between biliary atresia and other causes of prolonged neonatal jaundice. A simplified method of a laparoscopic-assisted cholecysto-cholangiography is presented. Retrospective chart review was conducted of all patients who from May 2002 to April 2012 underwent a laparoscopic-assisted cholecysto-cholangiography with routine fixation of the fundus of the gallbladder to the lateral aspect of the abdominal wall. A total of 18 infants (8 boys) aged 41-104 (median 64) days underwent laparoscopic-assisted cholecysto-cholangiography for prolonged jaundice. The technique identified ten cases of a patent bile duct system and eight biliary atresias. (Thirty-two cases of suspected biliary atresia were confirmed by laparoscopy alone.) Two cases required suturing of a bile leak at the puncture site. Hitching the gallbladder to the lateral abdominal wall is a simple method allowing an optimal radiographic assessment of the extra- and intra-hepatic bile duct anatomy.

Early data from the first population-wide breast cancer-specific registry in Hong Kong.

BACKGROUND: Current measures for breast cancer prevention and options for treatment adopted in Hong Kong are mainly based on research data and clinical evidence from overseas. It is essential to establish a cancer-specific registry to monitor the status of breast cancer in Hong Kong. OBJECTIVES: We summarized the current status of breast cancer in Hong Kong based on the data collected from Hong Kong Breast Cancer Registry (HKBCR). METHODS: Prevalent and newly diagnosed breast cancers (including in situ and invasive breast cancers) were registered in the HKBCR. Information on patient demographics, risk factors, medical information, and survival were analyzed and reported in this study. RESULTS: Data of 2,330 breast cancer patients were analyzed. We observed an earlier median age at diagnosis in Hong Kong than those reported in other countries. Distribution of cancer stage was: stage 0 (11.4%), stage I (31.4%), stage II (41%), stage III (12.5%), stage IV (0.8%), and unclassified (2.9%). The percentages of patients who received surgery, chemotherapy, radiation therapy, and endocrine therapy were 98.7, 67.9, 64.8, and 64.1%, respectively. At a median follow-up of 1.2 years, locoregional recurrence was recorded at 2%, distant recurrence at 2.8%, and breast-cancer-related mortality at 0.3%. CONCLUSIONS: The HKBCR serves as a surveillance program to monitor disease and treatment patterns. It is pivotal to support research for more effective breast cancer prevention and treatment strategies in Hong Kong.

Giant urethral diverticulum calculus presenting as scrotal abscess.

We report herein a patient with a urethral calculus associated with urethral diverticulum. A 39-year-old man presented with scrotal swelling and acute retention of urine. Computed tomography of the pelvis and cystoscopy demonstrated a giant calculus in the proximal penile urethra. Emergency in-situ lithotripsy was performed. Complete stone clearance was achieved and a large urethral diverticulum was encountered. The rare occurrence of urethral diverticulum and associated stone disease were discussed.

Abrogated expression of DEC1 during oesophageal squamous cell carcinoma progression is age- and family history-related and significantly associated with lymph node metastasis.

BACKGROUND: Oesophageal squamous cell carcinoma (SCC) causes the highest number of cancer deaths in some regions of Northern China. Previously, we narrowed down a critical region at 9q33-34, identified to be associated with tumour-suppressive function of deleted in oesophageal cancer 1 (DEC1) in oesophageal SCC. METHODS: We generated DEC1 antibody and constructed tissue microarrays (TMAs) utilising tissue specimens from Henan, a high-risk region for oesophageal SCC, to investigate the importance of DEC1 expression in this cancer. RESULTS: Tissue microarray immunohistochemical staining reveals significant loss of DEC1 from hyperplasia, to tumour, and to lymph node metastasis. In addition, the loss of DEC1 in tumour is age-dependent. Interestingly, there is significant abrogation of DEC1 expression in patients with a family history of oesophageal SCC. Deleted in oesophageal cancer 1 localises to both the cytoplasm and nucleus. The vesicular pattern of DEC1 in the cytoplasm appears to localise at the Golgi and Golgi-endoplasmic reticulum intermediate compartment. CONCLUSION: This is the first TMA study to suggest a clinical association of DEC1 in lymph node metastatic oesophageal SCC, early onset oesophageal SCC and familial oesophageal SCC development. Subcellular localisation of DEC1 and its expression in oesophageal SCC tissues provide important insight for further deciphering the molecular mechanism of DEC1 in oesophageal SCC development.