Nanomolar phosphate supply and its recycling drive net community production in the subtropical North Pacific.

Seasonal drawdown of dissolved inorganic carbon (DIC) in the subtropical upper ocean makes a significant contribution to net community production (NCP) globally. Although NCP requires macronutrient supply, surface macronutrients are chronically depleted, and their supply has been unable to balance the NCP demand. Here, we report nanomolar increases in surface nitrate plus nitrite (N+N, ~20 nM) and phosphate (PO4, ~15 nM) from summer to winter in the western subtropical North Pacific. Molar ratios of upward fluxes of DIC:N+N:PO4 to the euphotic zone (< 100 m) were in near-stoichiometric balance with microbial C:N:P ratios (107~243:16~35:1). Comparison of these upward influxes with other atmospheric and marine sources demonstrated that total supply is largely driven by the other sources for C and N (93~96%), but not for P (10%), suggesting that nanomolar upward supply of P and its preferential recycling play a vital role in sustaining the NCP.

Emergence of Anthropogenic Signals in the Ocean Carbon Cycle.

Attribution of anthropogenically-forced trends in the climate system requires understanding when and how such signals will emerge from natural variability. We apply time-of-emergence diagnostics to a Large Ensemble of an Earth System Model, providing both a conceptual framework for interpreting the detectability of anthropogenic impacts in the ocean carbon cycle and observational sampling strategies required to achieve detection. We find emergence timescales ranging from under a decade to over a century, a consequence of the time-lag between chemical and radiative impacts of rising atmospheric CO2 on the ocean. Processes sensitive to carbonate-chemical changes emerge rapidly, such as impacts of acidification on the calcium-carbonate pump (10 years for the globally-integrated signal, 9-18 years regionally-integrated), and the invasion flux of anthropogenic CO2 into the ocean (14 globally, 13-26 regionally). Processes sensitive to the ocean's physical state, such as the soft-tissue pump, which depends on nutrients supplied through circulation, emerge decades later (23 globally, 27-85 regionally).

The oceanic sink for anthropogenic CO2 from 1994 to 2007.

We quantify the oceanic sink for anthropogenic carbon dioxide (CO2) over the period 1994 to 2007 by using observations from the global repeat hydrography program and contrasting them to observations from the 1990s. Using a linear regression-based method, we find a global increase in the anthropogenic CO2 inventory of 34 ± 4 petagrams of carbon (Pg C) between 1994 and 2007. This is equivalent to an average uptake rate of 2.6 ± 0.3 Pg C year-1 and represents 31 ± 4% of the global anthropogenic CO2 emissions over this period. Although this global ocean sink estimate is consistent with the expectation of the ocean uptake having increased in proportion to the rise in atmospheric CO2, substantial regional differences in storage rate are found, likely owing to climate variability-driven changes in ocean circulation.

A feasibility study of independent verification of dose calculation for Vero4DRT using a Clarkson-based algorithm.

Dose verification for a gimbal-mounted image-guided radiotherapy system, Vero4DRT (Mitsubishi Heavy Industries Ltd., Tokyo, Japan) is usually carried out by pretreatment measurement. Independent verification calculations using Monte Carlo methods for Vero4DRT have been published. As the Clarkson method is faster and easier to use than measurement and Monte Carlo methods, we evaluated the accuracy of an independent calculation verification program and its feasibility as a secondary check for Vero4DRT. Computed tomography (CT)-based dose calculation was performed using a modified Clarkson-based algorithm. In this study, 120 patients' treatment plans were collected in our institute. The treatments were performed using conventional irradiation for lung and prostate, 3-dimensional (3D) conformal stereotactic body radiotherapy (SBRT) for the lung, and intensity-modulated radiation therapy (IMRT) for the prostate. Differences between the treatment planning system (TPS) and the Clarkson-based independent dose verification software were computed, and confidence limits (CLs, mean ± 2 standard deviation %) for Vero4DRT were compared with the CLs for the C-arms linear accelerators in the previous study. The results of the CLs, the conventional irradiation, SBRT, and IMRT showed 2.2 ± 3.5% (CL of the C-arms linear accelerators: 2.4 ± 5.3%), 1.1 ± 1.7% (-0.3 ± 2.0%), 4.8 ± 3.7% (5.4 ± 5.3%), and -0.5 ± 2.5% (-0.1 ± 3.6%) differences, respectively. The dose disagreement between the TPS and CT-based independent dose verification software was less than the 5% action level of American Association of Physicists in Medicine (AAPM) Task Group 114 (TG114). The CLs for the gimbal-mounted Vero4DRT were similar to the deviations for C-arms linear accelerators.

Rapid decline in pH of coral calcification fluid due to incorporation of anthropogenic CO2.

Marine calcifying organisms, such as stony corals, are under threat by rapid ocean acidification (OA) arising from the oceanic uptake of anthropogenic CO2. To better understand how organisms and ecosystems will adapt to or be damaged by the resulting environmental changes, field observations are crucial. Here, we show clear evidence, based on boron isotopic ratio (δ11B) measurements, that OA is affecting the pH of the calcification fluid (pHCF) in Porites corals within the western North Pacific Subtropical Gyre at two separate locations, Chichijima Island (Ogasawara Archipelago) and Kikaijima Island. Corals from each location have displayed a rapid decline in δ11B since 1960. A comparison with the pH of the ambient seawater (pHSW) near these islands, estimated from a large number of shipboard measurements of seawater CO2 chemistry and atmospheric CO2, indicates that pHCF is sensitive to changes in pHSW. This suggests that the calcification fluid of corals will become less supersaturated with respect to aragonite by the middle of this century (pHCF = ~8.3 when pHSW = ~8.0 in 2050), earlier than previously expected, despite the pHCF-upregulating mechanism of corals.

The formation of the ocean's anthropogenic carbon reservoir.

The shallow overturning circulation of the oceans transports heat from the tropics to the mid-latitudes. This overturning also influences the uptake and storage of anthropogenic carbon (Cant). We demonstrate this by quantifying the relative importance of ocean thermodynamics, circulation and biogeochemistry in a global biochemistry and circulation model. Almost 2/3 of the Cant ocean uptake enters via gas exchange in waters that are lighter than the base of the ventilated thermocline. However, almost 2/3 of the excess Cant is stored below the thermocline. Our analysis shows that subtropical waters are a dominant component in the formation of subpolar waters and that these water masses essentially form a common Cant reservoir. This new method developed and presented here is intrinsically Lagrangian, as it by construction only considers the velocity or transport of waters across isopycnals. More generally, our approach provides an integral framework for linking ocean thermodynamics with biogeochemistry.

Association of blood pressure control and metabolic syndrome with cardiovascular risk in elderly Japanese: JATOS study.

BACKGROUND: The impact of the metabolic syndrome (MS) on cardiovascular events in elderly subjects has not been clarified. We hypothesized that the impact differs between patients with and without strictly controlled blood pressure (BP) and also between early elderly (<75 years) and late (≥75 years) elderly patients. METHODS: Elderly hypertensive patients (65-85 years old) were randomly assigned to strict (target systolic BP <140 mm Hg) or mild (140-159 mm Hg) BP target, and were treated for 2 years with efonidipine-based regimen. MS was defined according to the National Cholesterol Education Program Adult Treatment Panel III criteria, except for the use of body mass index (BMI) ≥25 kg/m(2) instead of waist circumference. Primary endpoint was combined incidence of cardiovascular and renal events. Data were obtained from 2,865 patients. RESULTS: The prevalence of MS was 31.4%. The incidence of primary endpoint in patients with and without MS was 4.0% and 3.1%, respectively. MS was a significant risk factor for cardiovascular events in patients <75 years old (adjusted hazard ratio (HR) 2.17, P = 0.01), but not in patients ≥75 years old (adjusted HR 0.98, P = 0.94). In patients with MS, the event rate was significantly lower with strict treatment than with mild treatment among patients aged <75 years (P = 0.0006) but not in those aged ≥75 years (P = 0.82). CONCLUSIONS: MS was associated with cardiovascular risk in elderly hypertensive patients <75 years old, and strict BP control was beneficial for those with MS. However, MS and intensive control of BP may have little effect on cardiovascular events in elderly patients ≥75 years old.

Impact of renal function on cardiovascular events in elderly hypertensive patients treated with efonidipine.

This study evaluated the impact of renal function on cardiovascular outcomes in elderly hypertensive patients enrolled in the Japanese Trial to Assess Optimal Systolic Blood Pressure in Elderly Hypertensive patients. The patients were randomly assigned to either a strict-treatment group (target systolic blood pressure (BP) <140 mm Hg, n=2212) or a mild-treatment group (target systolic BP, 140 to <160 mm Hg, n=2206), each with efonidipine (a T/L-type Ca channel blocker)-based regimens. Cardiovascular events (stroke, cardiovascular disease and renal disease) were evaluated during the 2-year follow-up period following the prospective randomized open-blinded end-point method. Estimated glomerular filtration rate (eGFR) was elevated throughout the trial period in both the strict-treatment (59.4-62 ml min⁻¹ per 1.73 m²) and the mild-treatment group (58.8-61.4 ml min⁻¹ per 1.73 m²). This tendency was also observed in diabetic patients and patients aged ≥75 years, with baseline eGFR<60 ml min⁻¹ per 1.73 m². Baseline eGFR (<60 vs. ≥60 ml min⁻¹ per 1.73 m²) had no definite relationship with the incidence of cardiovascular events, nor did the level of BP control. Proteinuria at the time of entry into the study, however, was significantly correlated with cardiovascular event rates (7.1%), an association that was more apparent in patients with eGFR<60 ml min⁻¹ per 1.73 m² (8.2%). Furthermore, the event rate was more elevated in patients with greater declines in eGFR and was amplified when the baseline eGFR was <60 ml min⁻¹ per 1.73 m². In conclusion, the rates of decline of renal function and proteinuria constitute critical risk factors for cardiovascular events in elderly hypertensive patients, trends that are enhanced when baseline eGFR is diminished. Furthermore, the fact that efonidipine-based regimens ameliorate renal function in elderly hypertensive patients with chronic kidney disease may offer novel information on the mechanisms of cardiovascular protection.

Comparison of strict- and mild-blood pressure control in elderly hypertensive patients: a per-protocol analysis of JATOS.

We performed a per-protocol analysis of the Japanese Trial to Assess Optimal Systolic Blood Pressure in Elderly Hypertensive Patients (JATOS) to evaluate the optimal target blood pressure (BP) in elderly hypertensive patients. In JATOS, conducted in elderly (65-85 years) hypertensive patients treated with efonidipine hydrochloride, there were no differences between the strict-treatment group (systolic BP maintained at <140 mm Hg) and the mild-treatment group (systolic BP maintained at ≥140 mm Hg and <160 mm Hg) in the incidence of primary end points (cardiovascular disease and renal failure) for 2 years. The present study analyzed data in subgroups of JATOS in which the average systolic BP was within the range of target values. The average BP levels achieved in the strict-target BP achieved subgroup (n=1191) and the mild-target BP achieved subgroup (n=1531) were 132.3/74.0 mm Hg and 146.6/78.3 mm Hg, respectively. The incidences of primary end points were similar between these subgroups (11.1/1000 patients per year and 13.2/1000 patients per year, respectively, P=0.502), and there were also no differences in the incidences of adverse events. The incidences of cardiovascular events in patients who failed to achieve their respective treatment goals, on the other hand, were significantly higher than in patients who achieved them. These results indicate that strict treatment for elderly hypertensive patients may have little effect in enhancing the suppression of the onset of cardiovascular events as compared with mild treatment, although patients who have difficulties in achieving treatment goals should be given more aggressive treatment as a high-risk population.

Impact of electrocardiographic left ventricular hypertrophy on the occurrence of cardiovascular events in elderly hypertensive patients. - The Japanese trial to assess optimal systolic blood pressure in elderly hypertensive patients (JATOS) -.

BACKGROUND: Electrocardiographic (ECG) left ventricular hypertrophy (LVH) is a risk factor for cardiovascular events and the incidence of LVH increases with age. However, few studies have assessed risks associated with LVH in elderly hypertensive patients. METHODS AND RESULTS: The Japanese Trial to Assess Optimal Systolic Blood Pressure in Elderly Hypertensive Patients (JATOS) was conducted to determine optimal blood pressure in elderly patients. At study entry, the sum of the S-wave in lead V(1) and the R-wave in lead V(5) (SV1+ RV5) could be determined in 3,230 patients, among whom 164 (5.1%) had cardiovascular events. On univariate analysis, the hazard ratio for cardiovascular events was 1.51 for each 10 mm (=1 mV) (95% confidence interval (CI): 1.34-1.69, P<0.0001) when SV1+ RV5 was considered a continuous variable, and 2.17 (95%CI: 1.54-3.05, P<0.0001) and 2.83 (95%CI: 1.91-4.19, P<0.0001) when SV1+ RV5 was classified into 2 groups at threshold values of either 35 mm or 40 mm, respectively. Multivariate Cox analysis showed that gender, age, current smoking, diabetes mellitus, history of renal disease, history of stroke, and SV1+ RV5 were significantly related to the occurrence of cardiovascular events. Kaplan - Meier curves showed that increasing SV1+ RV5 values were associated with higher incidences of cardiovascular events. CONCLUSIONS: ECG LVH is strongly related to cardiovascular events in elderly hypertensive patients.

Nifedipine retard was as effective as angiotensin converting enzyme inhibitors in preventing cardiac events in high-risk hypertensive patients with diabetes and coronary artery disease: the Japan Multicenter Investigation for Cardiovascular Diseases-B (JMIC-B) subgroup analysis.

We stratified findings from the Japan Multicenter Investigation for Cardiovascular Diseases-B according to whether or not the patients had diabetes and compared the incidence of cardiac events occurring over a 3-year period between treatment with nifedipine retard and angiotensin converting enzyme (ACE) inhibitor. The primary endpoint was the overall incidence of cardiac events (cardiac death or sudden death, myocardial infarction, hospitalization for angina pectoris or heart failure, serious arrhythmia, and coronary interventions), and the secondary endpoints were a composite of other events (cerebrovascular accidents, worsening of renal dysfunction, non-cardiovascular events, and total mortality). The results showed no significant difference in the incidence of the primary endpoint between the nifedipine group (n=199) and the ACE inhibitor group (n=173) in diabetic patients: 15.08% vs. 15.03%, relative risk 1.06, p=0.838. Also in nondiabetic patients, no significant difference was observed between the former (n=629) and the latter (n=649): 13.67% vs. 12.33%, relative risk 1.04, p=0.792. Similar results were obtained for the incidence of the secondary endpoints: in diabetic patients, 5.03% vs. 5.20%, relative risk 0.89, p=0.799; in nondiabetic patients, 2.70% vs. 2.47%, relative risk 1.07, p=0.842. Achieved blood pressure levels were 138/76 and 136/77 mmHg in the nifedipine group and 140/78 and 138/79 mmHg in the ACE inhibitor group in diabetic and nondiabetic patients, respectively. This study showed that nifedipine retard was as effective as ACE inhibitors in reducing the incidence of cardiac events in extremely high-risk hypertensive patients with complications of diabetes and coronary artery disease.

Comparison of nifedipine retard with angiotensin converting enzyme inhibitors in Japanese hypertensive patients with coronary artery disease: the Japan Multicenter Investigation for Cardiovascular Diseases-B (JMIC-B) randomized trial.

The Japan Multicenter Investigation for Cardiovascular Diseases-B was performed to investigate whether nifedipine retard treatment was associated with a significantly higher incidence of cardiac events than angiotensin converting enzyme inhibitor treatment in Japanese patients. The study used a prospective, randomized, open, blinded endpoint (PROBE) design. Patients were enrolled at 354 Japanese hospitals specializing in cardiovascular disease. The subjects were 1,650 outpatients aged under 75 years who had diagnoses of both hypertension and coronary artery disease. There were 828 patients subjected to intention-to-treat analysis in the nifedipine retard group and 822 patients in the angiotensin converting enzyme inhibitor group. The patients were randomized to 3 years of treatment with either nifedipine retard or angiotensin converting enzyme inhibitor. The primary endpoint was the overall incidence of cardiac events (cardiac death or sudden death, myocardial infarction, hospitalization for angina pectoris or heart failure, serious arrhythmia, and coronary interventions). The primary endpoint occurred in 116 patients (14.0%) from the nifedipine retard group and 106 patients (12.9%) from the angiotensin converting enzyme inhibitor group (relative risk, 1.05; 95% confidence interval, 0.81-1.37; p = 0.75). In the Kaplan-Meier estimates, there were no significant differences between the two groups (log-rank test: p = 0.86). The incidence of cardiac events and mortality did not differ between the nifedipine retard and angiotensin converting enzyme inhibitor therapies. Nifedipine retard seems to be as effective as angiotensin converting enzyme inhibitors in reducing the incidence of cardiac events and mortality.

[Clinical profiles of new angiotensin II receptor blockers: telmisartan, olmesartan medoxomil, and irbesartan].

Clinical use of type 1 angiotensin II receptor blockers(ABRs) is rapidly increasing because of their high safety as well as excellent efficacy. Recent clinical trials have demonstrated that telmisartan at a daily dose of 20-80 mg, olmesartan medoxomil at 10-40 mg, and irbesartan at 150-300 mg are effective and safe for the treatment of essential hypertension, severe hypertension and hypertension associated with renal diseases. These ARBs are similar to ACE inhibitors in terms of antihypertensive efficacy, but lack the adverse effect of cough. Long-term effects should be compared among ARBs, ACE inhibitors, and other antihypertensive drugs.

Cardiac conduction and arrhythmia: insights from Nkx2.5 mutations in mouse and humans.

The phenotypes of cardiac conduction and rhythm disorders are very well characterized because of the large numbers of affected patients who seek medical treatment. The few disorders where the genetic basis is known has led to a commonly held notion that the abnormal function of ion pumps, channels and connexins (ICC) causes conduction defects and arrhythmias. Although probably true in general, the ICC-centric model underemphasizes alternative mechanisms involving the organization of cells or mechanisms of gene expression. NKX2.5 was one of the first cardiac transcription factors identified that when mutated causes congenital heart disease and conduction defects in human. We present two hypotheses for the pathogenesis of conduction defects and arrhythmias as caused by transcription factor haploinsufficiency that are alternatives to a strictly ICC-centric model. First, conduction defects may arise from anatomic underdevelopment of the conduction system in utero. Second, the cardiac arrhythmias associated with Nkx2.5 mutation may result from the non-uniform alteration in a population of cardiac myocytes of the levels of channel proteins, leading to increased electrical heterogeneity. We propose that consideration of the two alternative hypotheses, in addition to the traditional ICC-centric model, should lead to a richer understanding of cardiac conduction defects and arrhythmogenesis.

Increase in pulse pressure relates to diabetes mellitus and low HDL cholesterol, but not to hyperlipidemia in hypertensive patients aged 50 years or older.

Higher pulse pressure is associated with higher cardiovascular risk. We investigated the relationship between pulse pressure and known metabolic risk factors in hypertensive patients who had not experienced stroke or myocardial infarction. In a multicenter cross-sectional survey made in 1995, we registered 939 hypertensive patients aged > or = 50 years. Of these, 734 had never experienced stroke or myocardial infarction. We divided these 734 patients into two groups based on the value of their pulse pressures: 396 patients with a pulse pressure > or = 60 mmHg, and 338 patients with a pulse pressure<60 mmHg. The average pulse pressure value was 72 +/- 12 mmHg in the former group, and 49 +/- 8 mmHg in the latter group. The former group exhibited advanced age, a higher women-to-men ratio, lower high-density lipoprotein (HDL) cholesterol, and higher systolic and lower diastolic blood pressure. Diabetes mellitus (DM) and left ventricular hypertrophy were more frequently noticed in the former group than in the latter group. The prevalence of hyperlipidemia, however, was similar in the two groups. The association of pulse pressure with DM and low HDL cholesterol was statistically significant by multiple logistic analysis adjusted for age, sex, and other known cardiovascular risk factors. In conclusion, pulse pressure increases with advancing age. DM made a substantially larger contribution to the increase in pulse pressure than hyperlipidemia.

Accuracy and reliability of wrist-cuff devices for self-measurement of blood pressure.

OBJECT: Self-measurement of blood pressure (BP) might offer some advantages in diagnosis and therapeutic evaluation and in patient management of hypertension. Recently, wrist-cuff devices for self-measurement of BP have gained more than one-third of the world market share. In the present study, we validated wrist-cuff devices and compared the results between wrist- and arm-cuff devices. The factors affecting the accuracy of wrist-cuff devices were also studied. METHOD: The research group to assess the validity of automated blood pressure measuring device consisted of 13 institutes in Japan, which validated two wrist-cuff devices (WC-1 and WC-2) and two arm-cuff devices (AC-1 and AC-2). They used a crossover method, where the comparison was done between auscultation, by two observers by means of a double stethoscope on one arm and the device on the opposite arm or wrist. RESULTS: There was good inter-observer agreement for the auscultation method in each institute (systolic blood pressure (SBP), -0.1 +/- 2.8 mmHg; diastolic blood pressure (DBP), -0.1 +/- 2.6 mmHg, n = 498). The mean difference between auscultation and the device was minimal both in arm-cuff devices (mean difference for AC-1, 2.2/1.9 mmHg, n = 97 and for AC-2, 5.1/2.9 mmHg, n = 136, SBP/DBP) and wrist-cuff devices (mean difference for WC-1, -2.1/1.2 mmHg, n = 173 mmHg and for WC-2, -2.3/-5.6 mmHg, n = 92). The standard deviation of the difference (SDD) in wrist-cuff devices, however (SDD for WC-1, 9.7/7.3 mmHg and for WC-2, 10.2/8.6 mmHg), was larger than that of the arm-cuff devices (SDD for AC-1, 5.6/6.6 mmHg and for AC-2, 6.3/5.1 mmHg). Grading of AC-1 and AC-2 based on criteria of British Hypertension Society was A/A and B/A, respectively, while that of WC-1 and WC-2 was C/B and D/B, respectively. Using the same validation protocol, the results of validation for one device were divergent in each institute. In wrist-cuff devices, the BP value obtained in palmar flexion was significantly higher and that obtained in palmar dorsiflexion was significantly lower than that in palmar extension. In some cases, finger plethysmogram did not disappear during maximum inflation of the wrist-cuff (congruent with 250 mmHg), even in palmar extension and especially in palmar flexion, suggesting incomplete obstruction of radial and/or ulnar arteries during inflation. CONCLUSION: The results suggest that wrist-cuff devices in the present form are inadequate for self-measurement of blood pressure and, thus, are inadequate for general use or clinical and practical use. However, there is much possibility in wrist-cuff device and the accuracy and reliability of wrist-cuff device are warranted by an improvement of technology.