Sleep debt and prevalence of proteinuria in subjects with short sleep duration on weekdays: a cross-sectional study.

STUDY OBJECTIVE: Short sleep duration is a risk factor of chronic kidney disease, along with cardiovascular diseases and all-cause mortality. Several studies reported that many people sleep longer on weekends than on weekdays, suggesting that they should be compensated for their sleep debt on weekdays on the weekends. Few studies have reported the clinical impact of sleep debt on the kidney. METHODS: This cross-sectional study included 5799 employees of Osaka University who visited its Health Care Center for their annual health examinations and answered ≤ 6 h of sleep duration on weekdays. The independent variable was the sleep debt index defined as a gap in self-reported sleep duration (≤ 5, 5-6, 6-7, 7-8, 8-9, and ≥ 9 h) between weekdays and weekends, which was categorized into ≤ 0, + 1, + 2, + 3 and ≥+4. An association between the sleep debt index and a prevalence of proteinuria defined as dipstick proteinuria of ≥ 1 + was assessed using logistic regression models adjusting for clinically relevant factors. RESULTS: More than four-fifths of the subjects had a positive sleep debt index (≤ 0, + 1, + 2, + 3, and ≥+4 recorded for 19%, 36%, 28%, 11%, and 6%, respectively). The multivariable-adjusted logistic regression models showed the sleep debt index ≥ 3 + was significantly associated with the prevalence of proteinuria (sleep debt index ≤ 0, adjusted odds ratio 1.13 [0.77, 1.65]; + 1, 1.00 [reference]; + 2, 1.29 [0.93, 1.79]; + 3, 1.54 [1.02, 2.33]; ≥ + 4, 1.87 [1.15, 3.05]). CONCLUSIONS: Sleep debt was associated with the prevalence of proteinuria in a dose-dependent manner.

Vitamin E supplementation improves high-densitiy lipoprotein and endothelial functions in end-stage kidney disease patients undergoing hemodialysis
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BACKGROUND AND AIMS: Patients with end-stage kidney disease (ESKD) undergoing hemodialysis (HD) have been shown to be at increased risk for cardiovascular disease (CVD). Decreased high-density lipoprotein cholesterol (HDL-C) and impaired cholesterol efflux capacity (CEC) have been reported in such patients, and effects of vitamin E supplementation on HDL functions are poorly understood. Therefore, the present study aimed to investigate effects of vitamin E supplementation on HDL and endothelial functions in ESKD patients undergoing HD. We also assessed the influence of diabetes and haptoglobin (Hp) phenotype on the effects of vitamin E. MATERIALS AND METHODS: Vitamin E (300 mg daily) was supplemented for 12 weeks, followed by a 10-week washout phase in 40 ESKD patients undergoing HD (20 diabetic and 20 nondiabetic patients). HDL functions, including CEC, antioxidant capacity, and anti-inflammatory activity, were investigated. In diabetic patients, endothelial function, as represented by flow-mediated vasodilatation (FMD), was also assessed. The findings were compared according to diabetic condition or Hp phenotype. RESULTS: Vitamin E significantly increased CEC, whereas antioxidant capacity and anti-inflammatory activity remained unchanged. Further, the improvement in CEC was maintained after the 10-week washout phase. Endothelial function was significantly improved in diabetic patients. Subanalyses based on diabetes or Hp phenotype revealed that neither diabetes nor Hp phenotype influenced the effects of vitamin E. CONCLUSION: In ESKD patients undergoing hemodialysis, vitamin E supplementation significantly improved the HDL function of CEC and, in diabetic patients, endothelial function. These effects were independent of Hp phenotype.
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Effectiveness of rotavirus vaccines against hospitalisations in Japan.

BACKGROUND: In Japan, rotavirus hospitalisation occurs at a rate from 2.8 to 13.7 per 1000 child-years among children age less than 5 years, and it imposes a substantial burden to the healthcare system in the country. While both monovalent (RV1) and pentavalent (RV5) rotavirus vaccines are licensed in Japan, neither has been incorporated in the national infant immunization programme. In this study, we estimated vaccine effectiveness (VE) in Japan. METHODS: This study was conducted in Yuri-Kumiai General Hospital located in a city in the north-western part of Japan. Age-eligible children for rotavirus vaccination were enrolled if they were hospitalized for rotavirus gastroenteritis between September 2013 and August 2016. Rotavirus gastroenteritis was defined by the detection of rotavirus antigen by immunochromatography. "Vaccinated" was defined as infant inoculated with at least one dose of either RV1 or RV5. A conditional logistic regression analysis was performed by modelling the year of birth, year of admission, residence of the children and vaccination status, and by matching the age of cases with that of test-negative controls. The adjusted odds ratio of the vaccinated over unvaccinated was then used to calculate VE in the formula of (1 - adjusted odds ratio) × 100. RESULTS: Out of the 244 patients enrolled, rotavirus antigen was detected in 55 (22.5%) of whom 10 (18.2%) were vaccinated, whereas 94 (49.7%) of 189 test-negative controls were vaccinated. During the study period, the vaccine uptake rate in the controls increased from 36.2% to 61.8%. On the other hand, the vaccination coverage over the three years was 64.2% in Yuri-Honjo city (three quarters of the catchment), and 91.4% in Nikaho city (one quarter of the catchment). The VE was calculated to be 70.4% (95% confidence interval: 36.0-86.4%, P = 0.002). The point estimate of the VE was lower but its 95% confidence interval overlaps those of the efficacies obtained from clinical trials in Japan. CONCLUSION: The rotavirus vaccine was effective in the real-world setting in Japan as in the clinical trials, and the introduction of rotavirus vaccine in the national infant immunization schedule will substantially reduce the number of rotavirus gastroenteritis hospitalisation in Japan.

[A Case of Complete Pathological Response in a Patient with Locally Advanced Sigmoid Colon Cancer after FOLFOX IRI Chemotherapy].

A 61-year-old man with advanced sigmoid colon cancer was admitted to our hospital. Abdominal computed tomography (CT) revealed locally advanced sigmoid colon cancer, with suspected invasion of the bladder and small intestine. The clinical stage of the disease was T4b, N1, M0, and Stage III a, with wild-type KRAS expression. A transverse colostomy was performed because of the presence of a bowel obstruction. The patient received 4 courses of Leucovorin, 5-fluorouracil, oxaliplatin, and irinotecan (FOLFOXIRI). The size of the tumor and lymph nodes decreased noticeably after chemotherapy and laparoscopic high anterior resection with lymph node dissection. During this phase, the pathological stage of the disease was ypT0, N0, and Stage 0(no viable carcinoma cells, Grade 3). This result suggested that preoperative FOLFOXIRI chemotherapy is a useful regimen for the treatment of locally advanced colon cancer.

[A case of gastric cancer in which grade 2 treatment effects were obtained with preoperative two-week S-1 administration].

In our hospital, a clinical trial on the effects of preoperative 2-week S-1 administration for advanced gastric cancer is being conducted. A7 5-year-old man presented to our hospital with a type 2 tumor(poorly differentiated adenocarcinoma)in the pyloric antrum. Subpyloric lymph node enlargement and a c-T2(MP), N1, M0, Stage II A tumor (according to the gastric cancer handling agreement, 14th edition)were diagnosed, and S-1(100mg/day)was subsequently administered for 14 days. On day 15, we performed laparoscopy-assisted distal gastrectomy, with D2 dissection. Analysis of the resected specimen, ie the primary tumor and metastatic lymph nodes, confirmed the effect of the treatment as Grade 2, and revealed a type 2 gastric cancer of 30×20mm in size; this tumor was downstaged to yp-T1b(SM), N1, Stage I B. No adverse events associated with perioperative S-1 were observed, and the postoperative course was good. At the latest follow-up(6 years after treatment), no recurrence was observed.

Northern Hemisphere forcing of climatic cycles in Antarctica over the past 360,000 years.

The Milankovitch theory of climate change proposes that glacial-interglacial cycles are driven by changes in summer insolation at high northern latitudes. The timing of climate change in the Southern Hemisphere at glacial-interglacial transitions (which are known as terminations) relative to variations in summer insolation in the Northern Hemisphere is an important test of this hypothesis. So far, it has only been possible to apply this test to the most recent termination, because the dating uncertainty associated with older terminations is too large to allow phase relationships to be determined. Here we present a new chronology of Antarctic climate change over the past 360,000 years that is based on the ratio of oxygen to nitrogen molecules in air trapped in the Dome Fuji and Vostok ice cores. This ratio is a proxy for local summer insolation, and thus allows the chronology to be constructed by orbital tuning without the need to assume a lag between a climate record and an orbital parameter. The accuracy of the chronology allows us to examine the phase relationships between climate records from the ice cores and changes in insolation. Our results indicate that orbital-scale Antarctic climate change lags Northern Hemisphere insolation by a few millennia, and that the increases in Antarctic temperature and atmospheric carbon dioxide concentration during the last four terminations occurred within the rising phase of Northern Hemisphere summer insolation. These results support the Milankovitch theory that Northern Hemisphere summer insolation triggered the last four deglaciations.

Retroperitoneal schwannoma is characterized by a high incidence of cellular type and GFAP-immunoreactivity.

To clarify the clinicopathologic characteristics of retroperitoneal schwannomas, which are sometimes confused with other spindle cell tumors, 27 cases were studied microscopically and immunohistochemically. The 27 cases consisted of 17 females and 10 males, the ages of whom ranged from 31-79 (mean 57.4) years. Gross examination revealed well-demarcated, encapsulated tumors, 3-15 cm (mean 8 cm) in diameter. Microscopic review divided them into 13 cases of cellular/fascicular, 3 of conventional, 6 of intermediate, and 5 of ancient type. Cellular/fascicular schwannomas were composed of cellular fascicles of spindle cells, in which nuclear palisading, Antoni B area and cyst were unclear, while numerous foamy cells were intermingled. Immunohistochemical investigation revealed diffuse, strong positivity for S-100 protein and Sox10 in all tumors studied. In addition, glial fibrillary acidic protein (GFAP) was extensively expressed in 92% of the cellular/fascicular type, while it was less prominent in others. The present study suggests that retroperitoneal schwannoma often occurs in the middle-aged woman, grows to a large size, exhibits cellular/fascicular microscopic features in half of the cases, and may arise from GFAP-positive Schwann cells. The presence of hyalinized vessels and dense infiltration of foamy macrophages as well as diffuse immunoreactivity for S-100 protein and Sox10 are helpful for the differential diagnosis.

Occupational sedentary behavior and prediction of proteinuria in young to middle-aged adults: a retrospective cohort study.

BACKGROUND: Although sedentary behavior is a risk factor of cardiometabolic diseases and mortality, little information is available about a clinical impact of occupational sedentary behavior on chronic kidney disease (CKD). METHODS: The present retrospective cohort study included 10,212 workers of a national university in Japan who underwent annual health checkups between April 2006 and March 2013. Main exposure of interest was self-reported occupational sedentary behavior at the baseline visit. The outcome was the incidence of proteinuria defined as dipstick urinary protein of 1 + or more. The association between sedentary workers and the incidence of proteinuria was assessed using Cox proportional hazards models adjusting for clinically relevant factors, including television viewing time, the major home sedentary behavior. RESULTS: During median 4.8 years (interquartile range 2.1-7.9) of the observational period, the incidence of proteinuria was observed in 597 (12.0%) males and 697 (13.3%) females. In males, sedentary workers were identified as a significant predictor of proteinuria (multivariable-adjusted hazard ratio of non-sedentary and sedentary workers: 1.00 [reference] and 1.35 [1.11-1.63]), along with longer television viewing time (< 30 min, 30-60 min, 1-2 h, 2-3 h, and > 3 h/day: 1.15 [0.93-1.42], 1.00 [reference], 1.24 [1.00-1.53], 1.41 [1.03-1.93], and 1.77 [1.13-2.76]), whereas not daily exercise time. In females, neither sedentary workers nor television viewing time was associated with the incidence of proteinuria. CONCLUSIONS: In conclusion, male sedentary workers were at high risk of proteinuria. Occupational sedentary behavior may be a potentially modifiable target for the prevention of CKD.

Frequency of alcohol drinking modifies the association between salt intake and albuminuria: a 1-year observational study.

Albuminuria is an important risk factor for end-stage kidney disease and cardiovascular mortality. This 1-year observational study aimed to assess the effect modification of alcohol drinking on the association between salt intake and albuminuria. Overall, 448 employees at a pharmaceutical company in Japan who underwent annual health checkups in both 2017 and 2018 were evaluated. The main exposure of interest was drinking frequency at their first checkups categorized as rarely, occasionally, and daily. To assess the association between the changes in salt intake and albuminuria, the differences in salt intake estimated from single-spot urine specimens and the urinary albumin-to-creatinine ratio (UACR) between 2017 and 2018 were calculated for each subject. A multivariable-adjusted linear regression model showed a significant association between ∆salt intake and ∆Log UACR (per 1 g/day of ∆salt intake, adjusted ß 0.16 [95% confidence interval 0.14, 0.19]) and an effect modification between drinking frequency and ∆salt intake (P for interaction = 0.088). The association between ∆salt intake and ∆Log UACR was enhanced by drinking frequency in a dose-dependent manner (per 1 g/day of ∆salt intake, adjusted ß 0.13 [0.06, 0.19], 0.16 [0.12, 0.20], and 0.20 [0.13, 0.27] in rare, occasional, and daily drinkers, respectively). In conclusion, the results of the present study indicated that salt-induced albuminuria was enhanced in subjects with higher drinking frequency, suggesting that salt restriction may have a stronger renoprotective effect in subjects with higher drinking frequency.

Frequency of Breakfast, Lunch, and Dinner and Incidence of Proteinuria: A Retrospective Cohort Study.

Although multiple studies have revealed a close association of skipping breakfast with cardiometabolic diseases, few studies have reported its association with chronic kidney disease (CKD). Furthermore, there is scant reporting on the clinical impacts that skipping lunch and dinner has on cardiometabolic diseases and CKD. This retrospective cohort study, including 5439 female and 4674 male workers of a national university in Japan who underwent annual health checkups between January 2005 and March 2013, aimed to assess an association of frequencies of breakfast, lunch, and dinner with incidence of proteinuria (dipstick urinary protein ≥1+). The incidence of proteinuria was observed in 763 (14.0%) females and 617 (13.2%) males during the median 4.3 and 5.9 years of the observational period, respectively. In females, skipping breakfast as well as skipping dinner, but not lunch, were associated with the incidence of proteinuria (adjusted hazard ratios of breakfast frequency of "every day", "sometimes", and "rarely": 1.00 (reference), 1.35 (1.09-1.66), and 1.54 (1.22-1.94), respectively; those of dinner frequency of "every day" and "≤sometimes": 1.00 (reference) and 1.31 (1.00-1.72), respectively). However, no association was observed in male workers. Skipping breakfast and skipping dinner were identified as risk factors of proteinuria in females, but not in males.

Body mass index modifies the association between frequency of alcohol consumption and incidence of hypertension in men but not in women: a retrospective cohort study.

Alcohol consumption is one of the major modifiable risk factors of hypertension. The aim of the present retrospective study was to assess the clinical impact of obesity on the association between alcohol consumption and the incidence of hypertension. The present study included 5116 male and 6077 female university employees with a median age of 32 (interquartile range 27-39) who underwent annual health checkups between January 2005 and March 2013. Self-reported drinking frequency was recorded at their first checkup and categorized into rarely and 1-3, 4-6, and 7 days/week. During the median observational period of 4.9 years (interquartile range 2.1-8.3), hypertension, defined as systolic/diastolic blood pressure of ≥140/90 mmHg and/or self-reported treatment for hypertension, was observed in 1067 (20.9%) men and 384 (6.3%) women. Poisson regression models adjusted for clinically relevant factors revealed a dose-dependent association between drinking frequency and the incidence of hypertension in men (adjusted incidence rate ratio [95% confidence interval] of men who drank rarely, 1-3, 4-6, and 7 days/week was 1.00 [reference], 1.12 [0.97-1.30], 1.42 [1.19-1.70], and 1.35 [1.14-1.59], respectively; Ptrend < 0.001). However, this association was not observed in women. The dose-dependent association was significant in nonobese men (body mass index (BMI) < 25 kg/m2), but not in obese men (BMI ≥25 kg/m2) (P for interaction between drinking frequency and BMI = 0.072). The present study provides clinically useful evidence to identify the drinkers who may reap the health benefits of abstinence from alcohol consumption.

Drinking frequency modifies an association between salt intake and blood pressure: A cohort study.

Salt sensitivity is one of the crucial risk factors of hypertension. The aim of the present prospective cohort study was to assess the clinical impact of alcohol drinking on an association between salt intake and blood pressure. The present study included 451 employees at a pharmaceutical company in Japan who underwent annual health checkups in both 2017 and 2018. The main exposure of interest was self-reported drinking frequency at their first checkups: rarely, occasionally, and daily. To assess the association between the change of salt intake estimated from single-spot urine specimens and that of blood pressure, the differences in systolic/diastolic blood pressure and salt intake between 2017 and 2018 were calculated for each subject. Multivariable-adjusted linear regression models adjusting for clinically relevant factors clarified a drinking frequency-dependent association between Δsalt intake and Δsystolic blood pressure (per 1 g/d of Δsalt intake adjusted ß [95% confidence interval] 0.19 [-0.73, 1.12], 0.84 [0.14, 1.53], and 1.78 [0.86, 2.69] in rare, occasional, and daily drinkers). A similar association between Δsalt intake and Δdiastolic blood pressure was also observed (-0.24 [-1.02, 0.54], 0.67 (0.18, 1.16), 0.95 [0.38, 1.51], in rare, occasional, and daily drinkers). The interactions between drinking frequency and Δsalt intake were found to be statistically significant (P for interaction = .028 and .006 for ∆systolic blood pressure and ∆diastolic blood pressure, respectively). The present study identified enhanced salt sensitivity in the subjects who drink at a higher frequency, suggesting that the reduction in alcohol consumption may improve salt sensitivity in higher frequency drinkers.

Evaluation of posttraumatic venous sinus occlusion with CT venography.

BACKGROUND: Although cerebral venous sinus occlusion (CVSO) is reported to be associated with intracranial hypertension, its incidence or significance in head trauma is not clear. This study investigated with CT venography the incidence of posttraumatic CVSO, its clinical course, and relation to intracranial hypertension. PATIENTS: This study comprised 97 consecutive patients admitted to our Trauma Center from 2002 through 2008 with skull fracture of the petrous portion of the temporal bone or that crossed the dural sinus. Patients with CVSO were examined with CT venography and followed up with CT venography or magnetic resonance imaging. The relation of CVSO to patient outcome and incidence of "talk and deteriorate" was also investigated. RESULTS: CVSO was observed in 22 of 97 patients (22.4%). Mortality was significantly higher in the CVSO group versus no-CVSO group (50.0% vs. 9.3%, p < 0.001). Incidence of lethal intracranial hypertension was higher in the CVSO versus no-CVSO group (40.9% vs. 5.3%, p < 0.001), although there was no difference in Glasgow Coma Scale score at admission between the two groups (CVSO group, 8 +/- 5 vs. no-CVSO group, 10 +/- 4). Recanalization without treatment for CVSO occurred by 6 months in 9 of the 11 survivors (81.8%) who could be followed up. CONCLUSION: CVSO incidence after head injury was much higher than ever thought. It was associated with mortality and lethal intracranial hypertension, indicating that CVSO may induce acute increase in intracranial pressure in some cases. Early recognition of CVSO may be important to predict deterioration after admission and for starting immediate treatment.

Lymphoepithelial cyst of the pancreas that was difficult to distinguish from branch duct-type intraductal papillary mucinous neoplasm: report of a case.

A 58-year-old woman was admitted to our hospital to optimize the management of her diabetes mellitus. A computed tomography (CT) scan showed a 30-mmdiameter, multilocular cyst in the head of the pancreas. The tumor markers, including DUPAN 2, SPAN-1, and carbohydrate antigen 19-9, were within the normal ranges. A contrast-enhanced CT scan showed a nonenhanced, multilocular cyst. Abdominal magnetic resonance imaging showed a multilocular cyst. Endoscopic retrograde cholangiopancreatography showed that the main pancreatic duct was normal. Based on these findings, we suspected a branch duct type intraductal papillary mucinous neoplasm. A distal pancreatectomy with a splenectomy was performed, since more of the mass was located on the dorsolateral side, inconsistent with the preoperative imaging results. On the resected specimen, a 4-cm-diameter, multilocular cyst containing serous fluid was found. Pathologically, the cyst wall was lined with squamous epithelium surrounded by abundant lymphoid tissue with follicles, consistent with a lymphoepithelial cyst of the pancreas, which is an unusual benign cyst.

Hepatobiliary cystadenoma exhibiting morphologic changes from simple hepatic cyst shown by 11-year follow up imagings.

BACKGROUND: A long-term follow up case of hepatobiliary cystadenoma originating from simple hepatic cyst is rare. CASE PRESENTATION: We report a case of progressive morphologic changes from simple hepatic cyst to hepatobiliary cystadenoma by 11 - year follow up imaging. A 25-year-old man visited our hospital in 1993 for a simple hepatic cyst. The cyst was located in the left lobe of the liver, was 6 cm in diameter, and did not exhibit calcification, septa or papillary projections. No surgical treatment was performed, although the cyst was observed to gradually enlarge upon subsequent examination. The patient was admitted to our hospital in 2004 due to epigastralgia. Re-examination of the simple hepatic cyst revealed mounting calcification and septa. Abdominal CT on admission revealed a hepatic cyst over 10 cm in diameter and a high-density area within the thickened wall. MRI revealed a mass of low intensity and partly high intensity on a T1-weighted image. Abdominal angiography revealed hypovascular tumor. The serum levels of AST and ALT were elevated slightly, but tumor markers were within normal ranges. Left lobectomy of the liver was performed with diagnosis of hepatobiliary cystadenoma or hepatobiliary cystadenocarcinoma. The resected specimen had a solid component with papillary projections and the cyst was filled with liquid-like muddy bile. Histologically, the inner layer of the cyst was lined with columnar epithelium showing mild grade dysplasia. On the basis of these findings, hepatobiliary cystadenoma was diagnosed. CONCLUSION: We believe this case provides evidence of a simple hepatic cyst gradually changing into hepatobiliary cystadenoma.

[A case of disseminated bone marrow carcinosis with disseminated intravascular coagulation successfully controlled with S-1 after total gastrectomy for advanced gastric cancer].

Bone marrow carcinosis due to gastric cancer with disseminated intravascular coagulation(DIC)occurs suddenly, progresses rapidly, and has a very poor prognosis. In addition, physical status tends to be bad at the time of the episode, and palliative care is generally selected as the treatment method. The case was a 70-year-old woman who underwent total gastrectomy for scirrhous stomach cancer five years previously. She recently noticed gingival hemorrhage, and was referred to our hospital by a nearby doctor. As a result of her examination, she was diagnosed with disseminated bone marrow carcinosis as a postoperative recurrence of gastric cancer that resulted in DIC. We transfused blood platelets and fresh frozen plasma into her, and controlled the bleeding tendency temporarily. She was started on oral administration of S-1 for improvement of DIC, and the therapy was successful without loss of QOL. It is easy to continue S-1 therapy as chemotherapy in the outpatient department, because it is a matter of internal medicine.

Asynchrony between Antarctic temperature and CO2 associated with obliquity over the past 720,000 years.

The δD temperature proxy in Antarctic ice cores varies in parallel with CO2 through glacial cycles. However, these variables display a puzzling asynchrony. Well-dated records of Southern Ocean temperature will provide crucial information because the Southern Ocean is likely key in regulating CO2 variations. Here, we perform multiple isotopic analyses on an Antarctic ice core and estimate temperature variations at this site and in the oceanic moisture source over the past 720,000 years, which extend the longest records by 300,000 years. Antarctic temperature is affected by large variations in local insolation that are induced by obliquity. At the obliquity periodicity, the Antarctic and ocean temperatures lag annual mean insolation. Further, the magnitude of the phase lag is minimal during low eccentricity periods, suggesting that secular changes in the global carbon cycle and the ocean circulation modulate the phase relationship among temperatures, CO2 and insolation in the obliquity frequency band.

State dependence of climatic instability over the past 720,000 years from Antarctic ice cores and climate modeling.

Climatic variabilities on millennial and longer time scales with a bipolar seesaw pattern have been documented in paleoclimatic records, but their frequencies, relationships with mean climatic state, and mechanisms remain unclear. Understanding the processes and sensitivities that underlie these changes will underpin better understanding of the climate system and projections of its future change. We investigate the long-term characteristics of climatic variability using a new ice-core record from Dome Fuji, East Antarctica, combined with an existing long record from the Dome C ice core. Antarctic warming events over the past 720,000 years are most frequent when the Antarctic temperature is slightly below average on orbital time scales, equivalent to an intermediate climate during glacial periods, whereas interglacial and fully glaciated climates are unfavourable for a millennial-scale bipolar seesaw. Numerical experiments using a fully coupled atmosphere-ocean general circulation model with freshwater hosing in the northern North Atlantic showed that climate becomes most unstable in intermediate glacial conditions associated with large changes in sea ice and the Atlantic Meridional Overturning Circulation. Model sensitivity experiments suggest that the prerequisite for the most frequent climate instability with bipolar seesaw pattern during the late Pleistocene era is associated with reduced atmospheric CO2 concentration via global cooling and sea ice formation in the North Atlantic, in addition to extended Northern Hemisphere ice sheets.

A method for determination of methyl chloride concentration in air trapped in ice cores.

A method for measuring the concentration of methyl chloride (CH3Cl) in air trapped in an ice core was developed. The method combines the air extraction by milling the ice core samples under vacuum and the analysis of the extracted air with a cryogenic preconcentration/gas chromatograph/mass spectrometry system. The method was applied to air from Antarctic ice core samples estimated to have been formed in the pre-industrial and/or early industrial periods. The overall precision of the method deduced from duplicate ice core analyses was estimated to be better than +/-20 pptv. The measured CH3Cl concentration of 528+/-26 pptv was similar to the present-day concentration in the remote atmosphere as well as the CH3Cl concentration over the past 300 years obtained from Antarctic firn air and ice core analyses.