Significance of Hypofractionated Radiotherapy in Postoperative Irradiation for Breast Cancer: An Asian Multi-institutional Prospective Study.

AIMS: There is a need for the adequate distribution of healthcare resources in Southeast Asia. Many countries in the region have more patients with advanced breast cancer who are eligible for postmastectomy radiotherapy (PMRT). Therefore, it is critical that hypofractionated PMRT is effective in most of these patients. This study investigated the significance of postoperative hypofractionated radiotherapy in patients with breast cancer, including advanced breast cancer, in these countries. MATERIALS AND METHODS: Eighteen facilities in 10 Asian countries participated in this prospective, interventional, single-arm study. The study included two independent regimens: hypofractionated whole-breast irradiation (WBI) for patients who had undergone breast-conserving surgery and hypofractionated PMRT for patients who had undergone total mastectomy at a dose of 43.2 Gy in 16 fractions. In the hypofractionated WBI group, patients with high-grade factors received additional 8.1 Gy boost irradiation sessions for the tumour bed in three fractions. RESULTS: Between February 2013 and October 2019, 227 and 222 patients were enrolled in the hypofractionated WBI and hypofractionated PMRT groups, respectively. The median follow-up periods in the hypofractionated WBI and hypofractionated PMRT groups were 61 and 60 months, respectively. The 5-year locoregional control rates were 98.9% (95% confidence interval 97.4-100.0) and 96.3% (95% confidence interval 93.2-99.4) in the hypofractionated WBI and hypofractionated PMRT groups, respectively. Regarding adverse events, grade 3 acute dermatitis was observed in 2.2% and 4.9% of patients in the hypofractionated WBI and hypofractionated PMRT groups, respectively. However, no other adverse events were observed. CONCLUSION: Although further follow-up is required, hypofractionated radiotherapy regimens for postoperative patients with breast cancer in East and Southeast Asian countries are effective and safe. In particular, the proven efficacy of hypofractionated PMRT indicates that more patients with advanced breast cancer can receive appropriate care in these countries. Hypofractionated WBI and hypofractionated PMRT are reasonable approaches that can contain cancer care costs in these countries. Long-term observation is required to validate our findings.

Orbital haematoma after orbital fracture repair using silicone, polytetrafluorethylene, and poly-L-lactic acid/hydroxyapatite implants.

The purpose of this paper was to report the incidence of orbital haematoma formation following the repair of orbital fractures with silicone, polytetrafluorethylene (PTFE), and poly-L-lactic acid/hydroxyapatite (PLLA/HA) implants. This retrospective review examined 234 patients (235 sides) who underwent repair of orbital wall fractures over a six-year period. Of these, 36 patients received a silicone sheet; 49 patients received a silicone sheet with superimposed PTFE implant; and 149 patients (150 sides) received PTFE with or without an underlying PLLA/HA implant. Orbital haematomas were documented in 13 out of 36 patients (36.1%) who underwent fracture repair with a silicone sheet; seven out of 49 patients (14.3%) who had a silicone sheet with a superimposed PTFE implant; and three out of 150 sides (2.0%) with PTFE with or without underlying PLLA/HA. The difference in incidence of orbital haematoma formation was significant among the groups (p < 0.001, Pearson's chi squared test). In the silicone sheet group, haematomas formed within two weeks of surgery in 11 patients (84.6%). In the silicone sheet with superimposed PTFE implant group, five patients (71.4%) developed orbital haematomas no earlier than after two weeks postoperatively. This study showed that the incidence of orbital haematoma formation following orbital fracture repair is different among the implant materials. The use of PTFE and PLLA/HA implants may minimise this complication.

Dissipation-Based Quantum Sensing of Magnons with a Superconducting Qubit.

Hybrid quantum devices expand the tools and techniques available for quantum sensing in various fields. Here, we experimentally demonstrate quantum sensing of a steady-state magnon population in a magnetostatic mode of a ferrimagnetic crystal. Dispersively coupling the magnetostatic mode to a superconducting qubit allows for the detection of magnons using Ramsey interferometry with a sensitivity on the order of 10^{-3} magnons/sqrt[Hz]. The protocol is based on dissipation as dephasing via fluctuations in the magnetostatic mode reduces the qubit coherence proportionally to the number of magnons.

Breaking the trade-off between fast control and long lifetime of a superconducting qubit.

The rapid development in designs and fabrication techniques of superconducting qubits has made coherence times of qubits longer. In the future, however, the radiative decay of a qubit into its control line will be a fundamental limitation, imposing a trade-off between fast control and long lifetime of the qubit. Here, we break this trade-off by strongly coupling another superconducting qubit along the control line. This second qubit, which we call "Josephson quantum filter" (JQF), prevents the first qubit from emitting microwave photons and thus suppresses its relaxation, while transmitting large-amplitude control microwave pulses due to the saturation of the quantum filter, enabling fast qubit control. This device functions as an automatic decoupler between a qubit and its control line and could help in the realization of a large-scale superconducting quantum processor by reducing the heating of the qubit environment and the crosstalk between qubits.

A novel surgical strategy for the resection of duodenal gastrointestinal stromal tumours located close to the duodenal ampulla: a case report.

Although the optimal surgical procedure for the resection of duodenal gastrointestinal stromal tumours has not yet been characterised due to the low prevalence of these tumours and the anatomical complexity of the duodenopancreatic region, difficult surgical procedures such as pancreaticoduodenectomy are often proposed for stromal tumours located in the second portion of the duodenum. Our case report highlights a novel surgical strategy that can be implemented as an alternative to pancreaticoduodenectomy for such tumours close to the duodenal ampulla. A 70-year-old man incidentally diagnosed with a stromal tumour close to the duodenal ampulla in the second portion of the duodenum underwent local resection guided by an endoscopic nasobiliary drainage tube with primary closure. This tube was converted to a percutaneous trans-small intestinal biliary drainage tube during the procedure to prevent biliary leakage biliary stasis due to swelling of the duodenal ampulla. He also underwent a simple distal gastrectomy with Roux-en-Y reconstruction. This resulted in successful R0 resection. There were no procedure-related complications or post-surgery weight changes. Our simple novel surgical strategy may therefore be useful for avoiding pancreaticoduodenectomy and maintaining quality of life in patients with stromal tumours close to the duodenal ampulla.

Information-to-work conversion by Maxwell's demon in a superconducting circuit quantum electrodynamical system.

Information thermodynamics bridges information theory and statistical physics by connecting information content and entropy production through measurement and feedback control. Maxwell's demon is a hypothetical character that uses information about a system to reduce its entropy. Here we realize a Maxwell's demon acting on a superconducting quantum circuit. We implement quantum non-demolition projective measurement and feedback operation of a qubit and verify the generalized integral fluctuation theorem. We also evaluate the conversion efficiency from information gain to work in the feedback protocol. Our experiment constitutes a step toward experimental studies of quantum information thermodynamics in artificially made quantum machines.

Nonclassical Photon Number Distribution in a Superconducting Cavity under a Squeezed Drive.

A superconducting qubit in the strong dispersive regime of circuit quantum electrodynamics is a powerful probe for microwave photons in a cavity mode. In this regime, a qubit excitation spectrum is split into multiple peaks, with each peak corresponding to an individual photon number in the cavity (discrete ac Stark shift). Here, we measure the qubit spectrum in a cavity that is driven continuously with a squeezed vacuum generated by a Josephson parametric amplifier. By fitting the obtained spectrum with a model which takes into account the finite qubit excitation power, we determine the photon number distribution, which reveals an even-odd photon number oscillation and quantitatively fulfills Klyshko's criterion for nonclassicality.

'PrP systemic deposition disease': clinical and pathological characteristics of novel familial prion disease with 2-bp deletion in codon 178.

BACKGROUND AND PURPOSE: A novel TYPE of prion disease associated mainly with autonomic-sensory polyneuropathy was reported by us previously. METHODS: Here the autopsy pathology for patient 1 (the sister) and the clinical characteristics of her younger brother (patient 2) are newly reported. Polymerase chain reaction based restriction fragment length polymorphism analysis of the prion protein gene (PRNP) was performed on both patients and their father (normal control). RESULTS: Polymerase chain reaction based restriction fragment length polymorphism analysis revealed a 2-bp deletion (CT) in codon 178 that causes an additional variable 25 amino acids at the C terminal, from the mutation site to the premature stop codon at codon 203, in both patients 1 and 2 but not in their father. The autopsy of patient 1 showed remarkable prion protein (PrP) deposits in the sympathetic ganglion and peripheral nerves, correlated to her severe autonomic sensory failure. PrP deposits were also found in the central nervous system and peripheral organs such as the heart, lung, stomach, jejunum, ileum, colon, urinary bladder and adrenal gland. The symptoms and biopsy findings of patient 2 were nearly the same as those reported previously for patient 1. His cognitive function was well preserved, but autonomic functions were severely impaired. His biopsied samples showed PrP deposits in the sural nerve and nerve plexuses of the stomach and colon. CONCLUSION: The present unique 2-bp deletion (CT) in codon 178 induced a 'PrP systemic deposition disease' such as pan-autonomic failure, sensory neuropathy and mild cognitive impairment with a specific pathology.

Interventions in the management of infection in the foot in diabetes: a systematic review.

The expert panel on diabetic foot infection (DFI) of the International Working Group on the Diabetic Foot conducted a systematic review seeking all published reports relating to any type of treatment for infection of the foot in persons with diabetes published as of 30 June 2014. This review, conducted with both PubMed and EMBASE, was used to update an earlier one undertaken on 30 June 2010 using the same search string. Eligible publications included those that had outcome measures reported for both a treated and a control population that were managed either at the same time, or as part of a before-and-after case design. We did not include studies that contained only information related to definition or diagnosis, but not treatment, of DFI. The current search identified just seven new articles meeting our criteria that were published since the 33 identified with the previous search, making a total of 40 articles from the world literature. The identified articles included 37 randomised controlled trials (RCTs) and three cohort studies with concurrent controls, and included studies on the use of surgical procedures, topical antiseptics, negative pressure wound therapy and hyperbaric oxygen. Among the studies were 15 RCTs that compared outcomes of treatment with new antibiotic preparations compared with a conventional therapy in the management of skin and soft tissue infection. In addition, 10 RCTs and 1 cohort study compared different treatments for osteomyelitis in the diabetic foot. Results of comparisons of different antibiotic regimens generally demonstrated that newly introduced antibiotic regimens appeared to be as effective as conventional therapy (and also more cost-effective in one study), but one study failed to demonstrate non-inferiority of a new antibiotic compared with that of a standard agent. Overall, the available literature was both limited in both the number of studies and the quality of their design. Thus, our systematic review revealed little evidence upon which to make recommendations for treatment of DFIs. There is a great need for further well-designed trials that will provide robust data upon which to make decisions about the most appropriate treatment of both skin and soft tissue infection and osteomyelitis in diabetic patients.

Cognitive and affective functions in Alzheimer's disease patients with metabolic syndrome.

BACKGROUND AND PURPOSE: The influence of metabolic syndrome (MetS) on cognitive and affective functions in patients with Alzheimer's disease (AD) was examined. METHODS: A total of 570 AD patients were divided into two subgroups depending on waist circumference (WC) (normal versus achieving Japanese diagnostic criteria of MetS). Afterwards, the AD control subgroup was defined as those normal WC patients with no vascular risk factors (VRFs). The AD with MetS (AD-MetS) subgroup was defined as the MetS WC group who had two or more VRFs to qualify as having MetS. Cognitive and affective functions, insulin resistance, vascular endothelial function and white matter changes between AD-MetS and AD controls were compared. RESULTS: Scores on the Mini-Mental State Examination, Hasegawa Dementia Score-Revised, Frontal Assessment Battery and Montreal Cognitive Assessment were worse in the AD-MetS group than in AD controls, but the difference was not significant. Some analyses were conducted twice, once including all patients and once including only late-elderly patients. Scores on the Geriatric Depression Scale were found to be significantly higher for AD-MetS than for AD controls (all ages, late-elderly), as were those for apathy (late-elderly). Furthermore, both the homeostasis model assessment of insulin resistance and reactive hyperemia index scores were significantly worse in AD-MetS than in AD controls, whilst white matter changes showed a tendency to be worse. CONCLUSIONS: Greater cognitive and affective decline occurs in patients with AD-MetS than in those without. Further, insulin resistance and vascular endothelial dysfunction are strongly correlated with AD-MetS before pathological white matter changes can be observed.

Wide dynamic range neutron flux monitor having fast time response for the Large Helical Device.

A fast time response, wide dynamic range neutron flux monitor has been developed toward the LHD deuterium operation by using leading-edge signal processing technologies providing maximum counting rate up to ∼5 × 10(9) counts/s. Because a maximum total neutron emission rate over 1 × 10(16) n/s is predicted in neutral beam-heated LHD plasmas, fast response and wide dynamic range capabilities of the system are essential. Preliminary tests have demonstrated successful performance as a wide dynamic range monitor along the design.

Beneficial effects of hydrogen gas on porcine liver reperfusion injury with use of total vascular exclusion and active venous bypass.

BACKGROUND: Liver ischemia/reperfusion (I/R) injury is a high risk factor in liver transplantation and it influences graft survival. One of the major events during I/R injury is the generation of cytotoxic oxygen radicals. Recently, hydrogen gas has been reported to have antioxidant properties and protective effects against organ dysfunction induced by I/R injury. The aim of this study is to investigate effects of hydrogen on porcine liver reperfusion injury. MATERIALS AND METHODS: Six outbred pigs weighing 20 kg were used for the experiment. Under general anesthesia, the venous bypass between the left femoral vein and the splenic vein to the left jugular vein was made using a centrifugal pump. Then, we used a total vascular exclusion clamp (all in- and out-flow to the liver was clamped) for 60 minutes. Hydrogen (5 ppm) saturated with lactate Ringer's solution was prepared. This solution was infused through the portal vein just before reperfusion (hydrogen group). RESULTS: Aspartate aminotransferase levels in the control versus hydrogen group in 30, 60, and 120 minutes after reperfusion were 1560.3, 1925.3, and 2342.5 versus 175.3, 200.7, and 661.00 IU/L, respectively. Lactate dehydrogenase (LDH) levels in the control versus hydrogen groups in 30, 60, and 120 minutes after reperfusion were 23,235.0, 3496.7, and 4793.5 versus 663.3, 802.0, and 983.7 IU/L, respectively. The hydrogen gas level in liver tissue increased to 954.6 ppm immediately after reperfusion; however, it disappeared within 30 minutes. CONCLUSION: The solution containing hydrogen gas was safe and had remarkably protective effects on the porcine during liver I/R and may be applied in the clinical setting.

Rewarming preservation by organ perfusion system for donation after cardiac death liver grafts in pigs.

BACKGROUND: Use of grafts from donors after cardiac death (DCD) would greatly contribute to the expansion of the donor organ pool. However, this requires the development of novel preservation methods to recover the organ from changes due to warm ischemia time (WIT). METHODS: Porcine livers were perfused with a newly developed machine perfusion (MP) system. The livers were perfused with modified University of Wisconsin solution (UW) - gluconate. All grafts were procured after acute hemorrhagic shock with the ventilator off. For group 1 (n = 6), grafts were procured after WIT of 60 minutes and preserved by hypothermic MP (HMP) for 3 hours. For group 2 (n = 5), grafts were preserved with 2 hours of simple cold storage (SCS) and HMP for 2 hours. For group 3 (n = 6), grafts were preserved with 2 hours of SCS and rewarming up to 25°C by MP for 2 hours (RMP). The preserved liver grafts were transplanted orthotopically. RESULTS: The alanine aminotransferase level in perfusate in RMP during perfusion preservation was maintained at less than that of HMP. The levels of aspartate aminotransferase and lactate dehydrogenase in the 2 hours after reperfusion were significantly lower in group 3. Histologically, the necrosis of hepatocytes was less severe in group 3. The survival rate in group 3 was 2/4, but 0/4 in the other group. CONCLUSION: RMP is expected to facilitate the recovery of the DCD liver grafts.

Magnetic field shimming of a permanent magnet using a combination of pieces of permanent magnets and a single-channel shim coil for skeletal age assessment of children.

We adopted a combination of pieces of permanent magnets and a single-channel (SC) shim coil to shim the magnetic field in a magnetic resonance imaging system dedicated for skeletal age assessment of children. The target magnet was a 0.3-T open and compact permanent magnet tailored to the hand imaging of young children. The homogeneity of the magnetic field was first improved by shimming using pieces of permanent magnets. The residual local inhomogeneity was then compensated for by shimming using the SC shim coil. The effectiveness of the shimming was measured by imaging the left hands of human subjects and evaluating the image quality. The magnetic resonance images for the child subject clearly visualized anatomical structures of all bones necessary for skeletal age assessment, demonstrating the usefulness of combined shimming.

Adding to the mix: fibroblast growth factor and platelet-derived growth factor receptor pathways as targets in non-small cell lung cancer.

The treatment of advanced non � small cell lung cancer (NSCLC) increasingly involves the use of molecularly targeted therapy with activity against either the tumor directly, or indirectly, through activity against host-derived mechanisms of tumor support such as angiogenesis. The most well studied signaling pathway associated with angiogenesis is the vascular endothelial growth factor (VEGF) pathway, and the only antiangiogenic agent currently approved for the treatment of NSCLC is bevacizumab, an antibody targeted against VEGF. More recently, preclinical data supporting the role of fibroblast growth factor receptor (FGFR) and platelet-derived growth factor receptor (PDGFR) signaling in angiogenesis have been reported. The platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF) pathways may also stimulate tumor growth directly through activation of downstream mitogenic signaling cascades. In addition, 1 or both of these pathways have been associated with resistance to agents targeting the epidermal growth factor receptor (EGFR) and VEGF. A number of agents that target FGF and/or PDGF signaling are now in development for the treatment of NSCLC. This review will summarize the potential molecular roles of PDGFR and FGFR in tumor growth and angiogenesis, as well as discuss the current clinical status of PDGFR and FGFR inhibitors in clinical development.

Dominant-negative effects of a novel mutation in the filamin myopathy.

BACKGROUND: Filamin myopathy is associated with mutations in the filamin C gene (FLNC) and is a myofibrillar myopathy characterized by focal myofibrillar destruction and cytoplasmic aggregates containing several Z-disk-related proteins. METHODS: This study investigated 6 Japanese patients with dominantly inherited myofibrillar myopathy manifested by adult-onset, slow and progressive muscle weakness and atrophy in the distal extremities. RESULTS: The abundantly expressed proteins in the affected muscles were identified as filamin C by nano liquid chromatography-tandem mass spectrometry. A genetic analysis of FLNC identified a heterozygous c.8107delG mutation that was localized to the dimerization domain of filamin C. A biochemical crosslinking analysis of bacterially expressed recombinant wild-type and mutant filamin C fragments demonstrated that the mutant monomer disturbed the proper dimerization of the wild-type filamin dimer, resulting in formation of a heterotrimer with the wild-type filamin dimer. The expression study in C2C12 myoblasts showed that the mutant filamin fragments formed cytoplasmic aggregates with endogenous wild-type filamin C. CONCLUSIONS: This study provides evidence for the dominant-negative effects of the FLNC mutation. These effects may be mutation-specific and likely result in the variation in the clinical phenotypes seen in patients with filamin myopathy.

Common variants at the GCK, GCKR, G6PC2-ABCB11 and MTNR1B loci are associated with fasting glucose in two Asian populations.

AIMS/HYPOTHESIS: To test fasting glucose association at four loci recently identified or verified by genome-wide association (GWA) studies of European populations, we performed a replication study in two Asian populations. METHODS: We genotyped five common variants previously reported in Europeans: rs1799884 (GCK), rs780094 (GCKR), rs560887 (G6PC2-ABCB11) and both rs1387153 and rs10830963 (MTNR1B) in the general Japanese (n = 4,813) and Sri Lankan (n = 2,319) populations. To identify novel variants, we further examined genetic associations near each locus by using GWA scan data on 776 non-diabetic Japanese samples. RESULTS: Fasting glucose association was replicated for the five single nucleotide polymorphisms (SNPs) at p < 0.05 (one-tailed test) in South Asians (Sri Lankan) as well as in East Asians (Japanese). In fine-mapping by GWA scan data, we identified in the G6PC2-ABCB11 region a novel SNP, rs3755157, with significant association in Japanese (p = 2.6 x 10(-8)) and Sri Lankan (p = 0.001) populations. The strength of association was more prominent at rs3755157 than that of the original SNP rs560887, with allelic heterogeneity detected between the SNPs. On analysing the cumulative effect of associated SNPs, we found the per-allele gradients (beta = 0.055 and 0.069 mmol/l in Japanese and Sri Lankans, respectively) to be almost equivalent to those reported in Europeans. CONCLUSIONS/INTERPRETATION: Fasting glucose association at four tested loci was proven to be replicable across ethnic groups. Despite this overall consistency, ethnic diversity in the pattern and strength of linkage disequilibrium certainly exists and can help to appreciably reduce potential causal variants after GWA studies.