Build-up and dephasing of Floquet-Bloch bands on subcycle timescales.

Strong light fields have created opportunities to tailor novel functionalities of solids1-5. Floquet-Bloch states can form under periodic driving of electrons and enable exotic quantum phases6-15. On subcycle timescales, lightwaves can simultaneously drive intraband currents16-29 and interband transitions18,19,30,31, which enable high-harmonic generation16,18,19,21,22,25,28-30 and pave the way towards ultrafast electronics. Yet, the interplay of intraband and interband excitations and their relation to Floquet physics have been key open questions as dynamical aspects of Floquet states have remained elusive. Here we provide this link by visualizing the ultrafast build-up of Floquet-Bloch bands with time-resolved and angle-resolved photoemission spectroscopy. We drive surface states on a topological insulator32,33 with mid-infrared fields-strong enough for high-harmonic generation-and directly monitor the transient band structure with subcycle time resolution. Starting with strong intraband currents, we observe how Floquet sidebands emerge within a single optical cycle; intraband acceleration simultaneously proceeds in multiple sidebands until high-energy electrons scatter into bulk states and dissipation destroys the Floquet bands. Quantum non-equilibrium calculations explain the simultaneous occurrence of Floquet states with intraband and interband dynamics. Our joint experiment and theory study provides a direct time-domain view of Floquet physics and explores the fundamental frontiers of ultrafast band-structure engineering.

Tunable non-integer high-harmonic generation in a topological insulator.

When intense lightwaves accelerate electrons through a solid, the emerging high-order harmonic (HH) radiation offers key insights into the material1-11. Sub-optical-cycle dynamics-such as dynamical Bloch oscillations2-5, quasiparticle collisions6,12, valley pseudospin switching13 and heating of Dirac gases10-leave fingerprints in the HH spectra of conventional solids. Topologically non-trivial matter14,15 with invariants that are robust against imperfections has been predicted to support unconventional HH generation16-20. Here we experimentally demonstrate HH generation in a three-dimensional topological insulator-bismuth telluride. The frequency of the terahertz driving field sharply discriminates between HH generation from the bulk and from the topological surface, where the unique combination of long scattering times owing to spin-momentum locking17 and the quasi-relativistic dispersion enables unusually efficient HH generation. Intriguingly, all observed orders can be continuously shifted to arbitrary non-integer multiples of the driving frequency by varying the carrier-envelope phase of the driving field-in line with quantum theory. The anomalous Berry curvature warranted by the non-trivial topology enforces meandering ballistic trajectories of the Dirac fermions, causing a hallmark polarization pattern of the HH emission. Our study provides a platform to explore topology and relativistic quantum physics in strong-field control, and could lead to non-dissipative topological electronics at infrared frequencies.

The KANNO blood group system.

The KANNO blood group system (International Society of Blood Transfusion [ISBT] 037) includes one high-prevalence antigen, KANNO1, across ethnic groups. Sporadic KANNO1- cases among East and South Asians are theoretically estimated by the DNA database library. Anti-KANNO1 has been found most often among Japanese women with current or prior pregnancy. Thus far, there are no reported cases of hemolytic transfusion reaction or hemolytic disease of the fetus and newborn due to anti-KANNO1.

Cumulative incidence of femoral localized periosteal thickening (beaking) preceding atypical femoral fractures in patients with rheumatoid arthritis.

The incidence of localized periosteal thickening (LPT, also termed beaking) of the lateral cortex that often precedes an atypical femoral fracture (AFF) was not high in patients with rheumatoid arthritis (RA) but incomplete AFFs developed in two patients. Higher-dose prednisolone was a significant risk factor for LPT in patients with RA. INTRODUCTION: Atypical femoral fractures (AFFs) are stress fractures; bisphosphonate (BP) use is a major risk factor for the development of such fractures. Localized periosteal thickening (LPT, also termed beaking) of the lateral cortex often precedes a complete or incomplete AFF. We evaluated the incidence of latent LPT in patients with rheumatoid arthritis (RA), to evaluate LPT progression, and to define LPT risk factors. METHODS: A total of 254 patients with RA were included; all underwent annual X-ray evaluation, dual-energy X-ray absorptiometry, and analyses of serum and bone metabolic markers for 2-3 years. LPT of the lateral cortex was sought in femoral X-rays. RESULTS: The incidence of LPT was 2.4% (6/254). Among patients on both BP and prednisolone (PSL) at enrollment, the incidence was 2.3% (3/131). Two femurs of two patients with LPT developed incomplete AFFs; LPT was extensive and associated with endosteal thickening. One patient had been on BP and PSL and microscopic polyangiitis was comorbidity. The other was on a selective estrogen receptor modulator and PSL. A daily PSL dose >5 mg (OR 11.4; 95%CI 2.15-60.2; p = 0.004) and higher-dose methotrexate (OR 1.22; 95%CI 1.01-1.49; p = 0.043) were significant risk factors for LPT. CONCLUSIONS: The incidence of latent LPT was not high (2.4%) but incomplete AFFs developed in two RA patients. Higher-dose PSL because of a comorbid disease requiring glucocorticoid treatment other than RA or refractory RA were risk factors for LPT; X-ray screening for latent LPT would usefully prevent complete AFFs.

Determination of contrast medium dose for hepatic CT enhancement with improved body size dependency using a non-linear analysis based on pharmacokinetic principles.

AIM: To propose a pharmacokinetic non-linear analysis method to determine contrast medium (CM) dose for computed tomography (CT) hepatic enhancement to improve body size dependency and validate the proposed CM dose determination method through a clinical study. MATERIALS AND METHODS: Enhancement data of 105 patients who underwent hepatic dynamic CT with a fixed CM dose were analysed. From the analysis results, CM doses as a function of each of four body size indices (body weight [BW], lean body weight [LBW], blood volume [BV], and body surface area [BSA]) for achieving improved body size dependency were determined (proposed method), and the body size dependencies were simulated using the enhancement data from 105 patients. The proposed method was validated with a two-arm clinical study on BW. Body size dependency was evaluated using p-value of correlation coefficient between Body size indices and enhancements (p<0.05: significant dependency) and mean absolute error (MAE). RESULTS: The simulation showed that significant body size dependencies not considered by the conventional method can be improved by the proposed method. MAEs of BW, LBW, and BV were also significantly reduced (p<0.05). The clinical study with BW demonstrated a similar improvement to that in the simulation result. MAE was also significantly reduced (p<0.001). CONCLUSION: The proposed method demonstrated more improved BW, LBW, and BV dependence compared to the conventional method. Through the two-arm clinical study, the proposed method using BW only, without height information, is a suitable index for improving body size dependency.

Current status of integrating oncology and palliative care in Japan: a nationwide survey.

BACKGROUND: Palliative care (PC) is increasingly recognized as essential for oncology care, and several academic societies strongly recommend integrating oncology and palliative care (IOP) in daily practice. Similarly, the Japanese government encouraged the implementation of IOP through the Cancer Control Act of 2007; however, its detailed progress remains unclear. Therefore, this cross-sectional nationwide survey was conducted to investigate the current status and hospital executive physicians' perception of IOP. METHODS: The questionnaire was developed based on IOP indicators with international consensus. It was distributed to executive physicians at all government-designated cancer hospitals (DCHs, n = 399) and matched non-DCHs (n = 478) in November 2017 and the results were compared. RESULTS: In total, 269 (67.4%) DCHs and 259 (54.2%) non-DCHs responded. The number of PC resources in DCHs was significantly higher than those in non-DCHs (e.g., full-time PC physicians and nurses, 52.8% vs. 14.0%, p < 0.001; availability of outpatient PC service ≥3 days per week, 47.6% vs. 20.7%, p < 0.001). Routine symptom screening was more frequently performed in DCHs than in non-DCHs (65.1% vs. 34.7%, p < 0.001). Automatic trigger for PC referral availability was limited (e.g., referral using time trigger, 14.9% vs. 15.3%, p = 0.700). Education and research opportunities were seriously limited in both types of hospitals. Most executive physicians regarded IOP as beneficial for their patients (95.9% vs. 94.7%, p = 0.163) and were willing to facilitate an early referral to PC services (54.7% vs. 60.0%, p < 0.569); however, the majority faced challenges to increase the number of full-time PC staff, and < 30% were planning to increase the staff members. CONCLUSIONS: This survey highlighted a considerable number of IOP indicators met, particularly in DCHs probably due to the government policy. Further efforts are needed to address the serious research/educational gaps.

Social relationships and functional status among Japanese elderly adults living in a suburban area.

OBJECTIVES: Social relationships may help in maintaining functional status among older adults. This study examined the types of social relationships that were related to functional status among Japanese community-dwelling older adults. STUDY DESIGN: This is a prospective cohort study. METHODS: We used baseline data from 2008 and conducted follow-up surveys six years later. Participants included individuals older than 65 years who lived in a suburban community in Japan. The Index of Social Interaction measure was used to assess multiple elements of social relationships. Two functional status outcomes were set: (1) functional decline and (2) functional decline and mortality. A multiple logistic regression model was used to examine the association between social relationships and functional decline six years later. RESULTS: After controlling for age, sex, family structure and disease status in 2008, poor social curiosity (odds ratio [OR] = 1.31, 95% confidence interval [CI]: 1.02-1.69) and interaction (OR = 2.57, 95% CI: 1.20-5.51) were found to be associated with functional decline. Furthermore, social curiosity (OR = 1.39, 95% CI: 1.14-1.69) and interaction (OR = 2.84, 95% CI: 1.44-5.59) were also associated with the composite outcome. CONCLUSIONS: Social curiosity and interacting with others were significantly associated with functional status. Promotion of social interaction may be essential for preventing future need for care.

Preparation and evaluation of orally disintegrating tablets containing taste masked microparticles of acetaminophen.

In the present work, taste masked particles of acetaminophen (AAP), a highly soluble bitter tasting drug, were developed and ODT containing the taste masked particles were prepared. Taste masked particles of AAP were prepared using different amounts of tetraglycerol polyricinoleate (TGPR) and Eudragit ®E100. Although the drug content ratio and drug recovery decreased with increasing TGPR, drug release from AAP-CR100 particles containing a large amount of TGPR was mostly suppressed for 2 min. Hence, AAP-CR100 was incorporated into ODT as taste masked particles for AAP. Three major disintegrants were used for ODT, and it was confirmed that the tensile strength of all formulations showed applicable hardness for handling. The AAP-CR100-CP(40) formulation containing crospovidone showed the shortest disintegration time and the drug release from AAP-CR100-CP(40) into pH 6.8 test solution was suppressed compared with commercial AAP tablets. Because the drug release from AAP-CR100-CP(40) into the pH 1.2 test solution was rapid, it was suggested that drug release from AAP-CR100-CP(40) is suppressed in the oral cavity, and the drug is released promptly in the stomach. Thus AAP-CR100-CP(40) may be useful as an ODT in which the dissolution of AAP in the oral cavity is suppressed.

Randomized clinical trial of extensive intraoperative peritoneal lavage versus standard treatment for resectable advanced gastric cancer (CCOG 1102 trial).

BACKGROUND: A survival benefit of extensive intraoperative peritoneal lavage (EIPL) has been reported in patients with gastric cancer with positive peritoneal cytology. The hypothesis of this study was that EIPL may reduce peritoneal recurrence in patients with advanced gastric cancer who undergo surgery with curative intent. METHODS: This was an open-label, multi-institutional, randomized, phase 3 trial to assess the effects of EIPL versus standard treatment after curative gastrectomy for resectable gastric cancer of T3 status or above. The primary endpoint was disease-free survival (DFS); secondary endpoints were overall survival, peritoneal recurrence-free survival and incidence of adverse events. RESULTS: Between July 2011 and January 2014, 314 patients were enrolled from 15 institutions and 295 patients were analysed (145 and 150 in the EIPL and no-EIPL groups respectively). The 3-year DFS rate was 63·9 (95 per cent c.i. 55·5 to 71·2) per cent in the EIPL group and 59·7 (51·3 to 67·1) per cent in the control group (hazard ratio (HR) 0·81, 95 per cent c.i. 0·57 to 1·16; P = 0·249). The 3-year overall survival rate was 75·0 (67·1 to 81·3) per cent in the EIPL group and 73·7 (65·9 to 80·1) per cent in the control group (HR 0·91, 0·60 to 1·37; P = 0·634). Peritoneal recurrence-free survival was not significantly different between the two groups (HR 0·92, 0·62 to 1·36; P = 0·676). No intraoperative complications related to EIPL were observed. CONCLUSION: EIPL did not improve survival or peritoneal recurrence in patients who underwent gastrectomy for advanced gastric cancer. Registration number: 000005907 (http://www.umin.ac.jp/ctr/index.htm).

ANTECEDENTES: Se ha descrito que un lavado peritoneal extenso intraoperatorio (extensive intraoperative peritoneal lavage, EIPL) proporciona un beneficio en la supervivencia en pacientes con cáncer gástrico con citología peritoneal positiva. La hipótesis de este estudio era que el EIPL podría disminuir la recidiva peritoneal en pacientes con cáncer gástrico avanzado sometidos a cirugía con intención curativa. MÉTODOS: Ensayo clínico fase 3, abierto, multicéntrico y aleatorizado para evaluar los efectos de un lavado peritoneal extenso intraoperatorio (EIPL) frente a tratamiento estándar tras gastrectomía curativa por cáncer gástrico ≥T3 resecable. La variable de resultado primaria fue la supervivencia libre de enfermedad (disease-free survival, DFS), y las variables de resultado secundarias fueron la supervivencia global (overall survival, OS), la supervivencia libre de recidiva peritoneal y la incidencia de efectos adversos. RESULTADOS: Entre julio de 2011 y enero de 2014, se reclutaron 314 pacientes de 15 instituciones y se analizaron los datos de 295 pacientes (145 en el grupo con EIPL y 150 en el grupo sin EIPL). La DFS a los 3 años fue 63,9% (i.c. del 95% 55,5-71,2) en el grupo con EIPL y 59,7% (i.c. del 95% 51,3-67,1) en el grupo control (cociente de riesgos instantáneos, hazard ratio, HR 0,81 (i.c. del 95% 0,57-1,16), P = 0,249). La OS a los 3 años fue 75,0% (i.c. del 95% 67,1-81,3) en el grupo con EIPL y 73,7% (i.c. del 95% 65,9-80,1) en el grupo control (HR 0,91 i.c. del 95% 0,60-1,37), P = 0,634). No se observaron diferencias estadísticamente significativas entre los dos grupos en la supervivencia libre de recidiva peritoneal (P = 0,676, HR 0,92 (i.c. del 95% 0,62-1,36). No se observaron complicaciones intraoperatorias relacionadas con EIPL. CONCLUSIÓN: El EIPL no mejoró la supervivencia o la recidiva peritoneal en pacientes sometidos a gastrectomía por cáncer gástrico avanzado.

A cost-effectiveness analysis of maternal CYP2D6 genetic testing to guide treatment for postpartum pain and avert infant adverse events.

Mothers with a CYP2D6 ultrarapid metabolizer phenotype may expose their infants to risk of adverse events when taking codeine while breastfeeding, by producing more of the active metabolite, morphine. Pharmacogenetic testing may be a valuable tool to identify such mothers, but testing can be costly. The objective of the study was to determine the incremental costs of genotyping to avert neonatal adverse events during maternal pharmacotherapy. A cost-effectiveness analysis, using a decision model, was performed with a hypothetical cohort of prenatal subjects. Parameter estimates, costs and ranges for sensitivity analyses were ascertained from the literature and expert opinion. Sensitivity analyses were conducted to assess the robustness of the results. Probabilistic sensitivity analysis revealed an incremental cost-effectiveness (ICER) of $10 433 (Canadian dollars) for genotyping compared to no genotyping per adverse event averted. Results were sensitive to hospital admission costs. The ICER was lower when evaluating only subjects having caesarean deliveries or those from ethnic populations known to have a high prevalence of ultra-rapid metabolizers. Although genotyping to guide pharmacotherapy was not cost saving, the cost to avert an infant adverse event may represent good value for money in specific populations. With a growing demand for personalized medicine, these findings are relevant for decision makers, clinicians and patients.

Randomized clinical trial of duct-to-mucosa versus invagination pancreaticojejunostomy after pancreatoduodenectomy.

BACKGROUND: The postoperative pancreatic fistula (POPF) rate for duct-to-mucosa and invagination anastomosis after pancreatoduodenectomy is still debated. The aim of this RCT was to investigate the POPF rate for duct-to-mucosa versus invagination pancreaticojejunostomy. METHODS: Patients were stratified by pancreatic texture and diameter of the main pancreatic duct and randomized to the duct-to-mucosa or invagination group. The primary endpoint was the rate of clinically relevant POPF (defined as grade B or C). Secondary endpoints were suture material cost for pancreaticojejunostomy, drain insertion duration and duration of postoperative hospital stay. RESULTS: Some 120 patients undergoing pancreatoduodenectomy were included following consent. Clinically relevant POPF developed in six of 59 patients (10 per cent) in the invagination group and in 14 of 61 patients (23 per cent) in the duct-to-mucosa group (P = 0·077). Duration of drain insertion (6 versus 7 days respectively; P = 0·027) and postoperative hospital stay (19 versus 24 days; P = 0·015) were shorter in the invagination group. Subgroup analysis for 61 patients with a soft pancreas revealed a lower rate of clinically relevant POPF in the invagination group (10 per cent versus 42 per cent in the duct-to-mucosa group; P = 0·010). Among 20 patients with a clinically relevant POPF, the six patients in the invagination group had a shorter duration of drain insertion (38·5 days versus 49 days for 14 patients in the duct-to-mucosa group; P = 0·028) and postoperative hospital stay (42 versus 54·5 days respectively; P = 0·028). CONCLUSION: This study did not demonstrate a superiority of invagination over duct-to-mucosa pancreaticojejunostomy in the risk of POPF. However, in high-risk patients with a soft pancreas, invagination may reduce the risk of clinically relevant POPF compared with duct-to-mucosa. Registration number: UMIN000005890 (http://www.umin.ac.jp).

The B allele with a 5·8 kb deletion in intron 1 of the ABO gene is the major allele in Japanese individuals with Bm and A1 Bm phenotypes.

Bm and A1 Bm phenotypes are the most frequent ABO variants in the Japanese population. The B antigen on Bm red blood cells is only detectable by adsorption and elution tests, and plasma B-transferase activity is usually detected at half or less levels compared with that of common B. Recently, a B allele lacking an erythroid cell-specific transcription enhancer in intron 1 of the ABO gene was identified from individuals with Bm and A1 Bm phenotypes, which could explain the unique serologic properties of Bm . In the Japanese Red Cross Society, eight Blood Centers tested blood samples from donors throughout Japan and collected blood samples from 888 Bm and 415 A1 Bm individuals. DNA analysis revealed that 1300 of 1303 (99·77%) individuals had the B allele with a 5·8 kb deletion (c.28 + 5110_10889del), which included the enhancer element.

Interindividual responses to different exercise stimuli among insulin-resistant women.

We aimed to investigate which among 20 cardiometabolic and performance outcomes do and do not respond to high-intensity interval training (HIT), resistance training (RT), or concurrent training (CT) in insulin-resistant adult women. A secondary aim was to report the training-induced changes and the prevalence of non-responders. Forty-five insulin-resistant adult women were randomly assigned to one of the following 4 groups: HIT (39.2 ± 9.5 years [y]; body mass index [BMI], 29.3 ± 3.3; n = 14), RT (33.9 ± 9.3 y; BMI, 29.4 ± 5.5; n = 8), CT (43.3 ± 8.1 y; BMI, 29.1 ± 2.9; n = 10), and a control group (CG, 40.1 ± 11.4 y; BMI, 28.3 ± 3.5; n = 13). Nine body composition, 3 cardiovascular, 3 metabolic, and 5 performance outcomes were assessed at baseline and after 12 weeks of intervention. Considering all outcomes, the lowest number of total non-responses for one or more variables was found in the RT group, followed by the CT and HIT groups. Individuals in the CG group were classified as non-responders for almost all the variables. Moreover, there were several significant changes in body composition and metabolic parameters, including fasting glucose (HIT: -5.7, RT -5.1 mg/d), fasting insulin (HIT: -0.6, RT -0.6 µIU/mL), and HOMA-IR (HIT: -0.3, RT -0.4), in addition to improvements in cardiovascular and performance parameters. Also, there were significant differences among groups in the prevalence of non-responders for the variables where a non-response was detected. Overall, the study suggests that independent of the mode of training including volume and frequency, RT has an important ability to reduce the prevalence of non-response to improve the 20 outcomes of health and performance in insulin-resistant adult women.

Early results of a randomized two-by-two factorial phase II trial comparing neoadjuvant chemotherapy with two and four courses of cisplatin/S-1 and docetaxel/cisplatin/S-1 as neoadjuvant chemotherapy for locally advanced gastric cancer.

BACKGROUND: Neoadjuvant chemotherapy (NAC) is a promising method of improving the survival of resectable gastric cancer. Cisplatin/S-1 (CS) and docetaxel/cisplatin/S-1 (DCS) are both effective against metastatic gastric cancer. This report clarified the impact of these regimens on early endpoints, including the pathological responses, chemotherapy-related toxicities, and surgical results. METHODS: Patients with M0 and either T4 or T3 in case of junctional cancer or scirrhous type received two or four courses of cisplatin (60 mg/m2 at day 8)/S-1 (80 mg/m2 for 21 days with 1 week rest) or docetaxel (40 mg/m2 at day 1)/cisplatin (60 mg/m2 at day 1)/S-1 (80 mg/m2 for 14 days with 2 weeks rest) as NAC. Patients then underwent D2 gastrectomy and adjuvant S-1 chemotherapy for 1 year. The primary endpoint was the 3-year overall survival. RESULTS: Between October 2011 and September 2014, 132 patients were assigned to receive CS (n = 66; 33 in 2 courses and 33 in 4 courses) or DCS (n = 66; 33 in 2 courses and 33 in 4 courses). The respective major grade 3 or 4 hematological toxicities (CS/DCS) were leukocytopenia (14.1%/26.2%), neutropenia (29.7%/47.7%), anemia (14.1%/12.3%), and platelet reduction (3.1%/1.5%). The rate of pathological response, defined as a complete response or < 10% residual cancer remaining, was 19.4% in the CS group and 15.4% in the DCS group, and 15.6% in the two-course group and 19.0% in the 4-course group. The R0 resection rate was 72.7% in the CS group and 81.8% in the DCS group and 80.3% in the two-course group and the 74.2% in the four-course group. No treatment-related deaths were observed. CONCLUSIONS: Our results do not support three-drug therapy with a taxane over two-drug therapy, or any further treatment beyond two cycles as an attractive candidate for the test arm of NAC.

Prognostic value of sequencing-based minimal residual disease detection in patients with multiple myeloma who underwent autologous stem-cell transplantation.

BACKGROUND: Most patients with multiple myeloma (MM) are considered to be incurable, and relapse owing to minimal residual disease (MRD) is the main cause of death among these patients. Therefore, new technologies to assess deeper response are required. PATIENTS AND METHODS: We retrospectively analyzed 125 patients with MM who underwent high-dose melphalan plus autologous stem-cell transplantation (ASCT) to detect MRD in autograft/bone marrow (BM) cells using a next-generation sequencing (NGS)-based method and allele-specific oligonucleotide-polymerase chain reaction (ASO-PCR). RESULTS: NGS-based method was applicable to 90% and this method had at least one to two logs greater sensitivity compared to ASO-PCR. MRD negative by NGS [MRDNGS(-)] (defined as <10-6) in post-ASCT BM cases (n = 26) showed a significantly better progression-free survival (PFS) (96% at 4 years, P < 0.001) and overall survival (OS) (100% at 4 years, P =0.04) than MRDNGS(+) in post-ASCT BM cases (n = 25). When restricting the analysis to the 39 complete response cases, patients who were MRDNGS(-) (n = 24) showed a significantly better PFS than those that were MRDNGS(+) (n = 15) (P =0.02). Moreover, MRDNGS(-) in post-ASCT BM cases (n = 12) showed significantly a better PFS than MRDNGS(+) cases (n = 7) where MRD was not detected by ASO-PCR (P = 0.001). Patients whose autografts were negative by NGS-based MRD assessment (<10-7) (n = 19) had 92% PFS and 100% OS at 4 years post-ASCT. Conversely, the NGS-based MRD positive patients who received post-ASCT treatment using novel agents (n = 49) had a significantly better PFS (P = 0.001) and tended to have a better OS (P= 0.214) than those that were untreated (n = 33). CONCLUSIONS: Low level MRD detected by NGS-based platform but not ASO-PCR has significant prognostic value when assessing either the autograft product or BM cells post-ASCT.

Prognostic factors for survival in patients with pT1 N+ or T2-3 N0 gastric cancer in Japan.

BACKGROUND: The outcome for pT1 N+ or pT2-3 N0 gastric cancer is favourable, but some patients suffer from recurrent disease. The aim of this study was to identify prognostic factors in patients with pT1 N+ or pT2-3 N0 gastric cancer. METHODS: This was a multicentre, retrospective cohort study. All patients with pT1 N+ or pT2-3 N0 gastric cancer who underwent curative gastrectomy at five high-volume, specialized cancer centres in Japan between 2000 and 2008 were included. Demographic, clinical, surgical and pathological data were collected. Independent prognostic factors were identified using a Cox proportional hazards regression model. RESULTS: Some 1442 patients were included. The 5-year overall survival rate for patients with pT1 N+ or pT2-3 N0 gastric cancer was 92·0 per cent. Multivariable analysis for overall survival identified age (hazard ratio (HR) 2·67, 95 per cent c.i. 2·09 to 3·43), sex (HR 0·57, 0·39 to 0·83) and clinical tumour depth (cT) (HR 1·45, 1·06 to 1·98) as independent prognostic factors. CONCLUSION: Survival of patients with pT1 N+ or pT2-3 N0 gastric cancer is good. Age 65 years or above, male sex and cT2-4 category are associated with worse overall survival.

Randomized clinical trial comparing standard diet with perioperative oral immunonutrition in total gastrectomy for gastric cancer.

BACKGROUND: Total gastrectomy for gastric cancer is associated with excessive weight loss and decreased calorie intake. Nutritional support using eicosapentaenoic acid modulates immune function and limits catabolism in patients with advanced cancer, but its impact in the perioperative period is unclear. METHODS: This was a randomized phase III clinical trial of addition of eicosapentaenoic acid-rich nutrition to a standard diet in patients having total gastrectomy for gastric cancer. Patients were randomized to either a standard diet or standard diet with oral supplementation of an eicosapentaenoic acid (ProSure®), comprising 600 kcal with 2·2 g eicosapentaenoic acid, for 7 days before and 21 days after surgery. The primary endpoint was percentage bodyweight loss at 1 and 3 months after surgery. RESULTS: Of 127 eligible patients, 126 were randomized; 124 patients (61 standard diet, 63 supplemented diet) were analysed for safety and 123 (60 standard diet, 63 supplemented diet) for efficacy. Across both groups, all but three patients underwent total gastrectomy with Roux-en-Y reconstruction. Background factors were well balanced between the groups. Median compliance with the supplement in the immunonutrition group was 100 per cent before and 54 per cent after surgery. The surgical morbidity rate was 13 per cent in patients who received a standard diet and 14 per cent among those with a supplemented diet. Median bodyweight loss at 1 month after gastrectomy was 8·7 per cent without dietary supplementation and 8·5 per cent with eicosapentaenoic acid enrichment (P = 0·818, adjusted P = 1·000). Similarly, there was no difference between groups in percentage bodyweight loss at 3 months (P = 0·529, adjusted P = 1·000). CONCLUSION: Immunonutrition based on an eicosapentaenoic acid-enriched oral diet did not reduce bodyweight loss after total gastrectomy for gastric cancer compared with a standard diet. Registration number: UMIN000006380 ( http://www.umin.ac.jp/).

Airway basophils are increased and activated in eosinophilic asthma.

BACKGROUND: The impact of basophils on asthma pathogenesis remains largely unexplored, particularly in humans. Here, we evaluated the frequencies and activation status of basophils in the sputum of adult asthmatic patients and related our findings to other parameters of eosinophilic airway inflammation. METHODS: We enrolled 44 adult asthmatic patients who were being treated with inhaled corticosteroids (ICS). Analysis of the induced sputum, exhaled nitric oxide fraction (FeNO) measurement, and asthma control test (ACT) were carried out together with standard blood and pulmonary function tests. The cellular composition of the sputum was examined by flow cytometry, and the phenotypes of blood and sputum basophils were compared. RESULTS: Basophils were increased in the sputum of asthmatic patients. The expression of CD203c on sputum basophils was significantly higher than that on blood basophils. The percentage of sputum basophils was positively correlated with those of eosinophils and mast cells; it was also correlated with that of blood eosinophils and FeNO. However, sputum basophils were not correlated with serum IgE, lung function, or the percentage of blood basophils. A receiver-operating characteristic (ROC) curve showed the superiority of sputum basophils as a surrogate marker of the percentages of sputum eosinophils compared with absolute numbers of blood eosinophils and FeNO. CONCLUSION: The number of activated basophils was increased in the sputum of patients with eosinophilic asthma and correlated with airway and blood eosinophils. Our observations suggest that sputum basophils may serve as a biomarker to monitor new therapeutic approaches for the treatment of eosinophilic asthma.

Singlet fission in pancake-bonded systems.

We theoretically investigate the potential of pancake-bonded systems for efficient singlet fission by examining phenalenyl radical dimer and tetramer models. In the dimer model, we propose an efficient way to satisfy the excitation energy level matching required for singlet fission by tuning the diradical character by changing the intermolecular distance. In the tetramer model, electronic couplings required for both singlet fission and charge mobility are found to be maximized simultaneously in the face-to-face configuration, which is usually known to be difficult to achieve due to a trade-off relationship between them in conventional π-conjugated molecules like pentacene. In addition, on the basis of the quasi-degenerate second-order perturbation analysis, we obtain a simplified and more efficient crystal-structure design guideline that pancake-bonded systems cause highly-active singlet fission.