bluuebunny/crossref_metadata_2025 huggingface dataset:
Williams-Beuren Syndrome Is a Genetic Disorder Associated with Impaired Glucose Tolerance and Diabetes in Childhood and Adolescence: New Insights from a Longitudinal Study
Authors: Stagi Stefano , Lapi Elisabetta , Cecchi Cecilia , Chiarelli Francesco , D'Avanzo Maria Gabriella , Seminara Salvatore , de Martino Maurizio
Published: June 2014

Background: In adults with Williams-Beuren syndrome (WBS), a common endocrine abnormality is type 2 diabetes mellitus (T2DM) or impaired glucose tolerance (IGT). However, few and sporadic data are available in children, adolescents, and young adults with WBS. Aim: To evaluate the frequency of IGT and T2DM in a cohort of children and young patients with WBS. Patients and Methods: We longitudinally evaluated 27 patients (9 males and 18 females, median age at study onset 13.6 years) with WBS. The median follow-up was 3.6 years. Variables of insulin resistance and β-cell function were evaluated in all subjects using an oral glucose tolerance test. The homeostasis model assessment (HOMA) of insulin resistance and the Matsuda index of insulin sensitivity were calculated. The study of the GCK and HNF1Α genes was performed in patients with glucose metabolism abnormalities. 45 age- and sex-matched healthy subjects and 51 age-, sex- and BMI-matched subjects were recruited as two control groups. Results: Considering nutritional status, 7 (25.9%) patients were obese, 9 (33.3%) overweight, and 11 (40.8%) normal-weight. One (3.1%) patient had acanthosis nigricans. IGT was diagnosed in 7 (25.9%) WBS patients and T2DM in 3 (11.1%). Considering all WBS patients, the median value of HOMA was 5.23 (range 2.93-14.89; insulin 24.73 ± 14.67 μU/ml; glucose 104.98 ± 16.06 mg/dl). Considering BMI values, HOMA was 11.00 (range 6.53-12.56), 5.64 (range 3.54-7.95), and 4.54 (range 3.21-5.43), and insulin was 34.53 ± 6.84, 22.76 ± 8.91, and 19.47 ± 6.01 μU/ml in obese, overweight, and normal-weight WBS patients, respectively. Comparing the results with the two control groups, WBS patients showed higher insulin values than healthy controls (p < 0.001), but similar values as the BMI-matched control group (p = n.s.). However, WBS patients showed significantly higher values of glycemia (healthy control group, p < 0.001; BMI-matched control group, p < 0.05) and HOMA (healthy control group, p < 0.001; BMI-matched control group, p < 0.05) than the two control groups. Finally, among WBS patients there was a higher number of subjects with IGT and T2DM than among healthy controls (p < 0.0001) and the BMI-matched control group (p = 0.0002). Conclusion: Our data strongly suggest that IGT and T2DM may be frequently discovered in children, adolescents, and young adults with WBS. WBS should be included among the genetic syndromes associated with T2DM. Further studies are necessary to evaluate the etiopathogenesis of this aspect.
Low Adherence to Upfront and Extended Adjuvant Letrozole Therapy among Early Breast Cancer Patients in a Clinical Practice Setting
Authors: Lee Hye-Suk , Lee Ju-Yeun , Ah Young-Mi , Kim Hyang-Sook , Im Seock-Ah , Noh Dong-Young , Lee Byung Koo
Published: June 2014

Objective: The aim of this study was to investigate the prevalence and causes of early discontinuation and non-adherence to upfront and extended adjuvant letrozole therapy in breast cancer patients. Methods: Adherence was assessed using medical charts and longitudinal pharmacy records of 609 patients who initiated adjuvant letrozole between January 2002 and April 2011. A Cox proportional hazards regression model was adopted to identify potential predictors of non-adherence. Results: The overall adherence rate after 1 year of therapy was 79.5%, with cumulative rates declining to 63.7% after 3 years and 57.1% after 5 years. A significantly lower rate of adherence in the extended adjuvant group was observed compared with the upfront adjuvant group (49.0 vs. 72.5%, p < 0.001). Adverse events (50.4%) were the major cause of early discontinuation, with musculoskeletal pain (73.2%) being the single most cited reason. Additional factors correlating with non-adherence in the upfront adjuvant group included a delay in initiation of adjuvant hormone therapy, breast-conserving surgery, calcium supplements, bisphosphonate therapy and concomitant medication for co-morbidity. Conclusions: We observed that approximately 57% of patients fully adhered to letrozole therapy over a 5-year treatment period, and that the adherence to extended letrozole was meaningfully lower than the upfront adjuvant letrozole in a clinical practice setting.
Loss of E-Cadherin Expression Is Associated with a Poor Prognosis in Stage III Colorectal Cancer
Authors: Yun Jung-A , Kim Seok-Hyung , Hong Hye Kyung , Yun Seong Hyeon , Kim Hee Cheol , Chun Ho-Kyung , Cho Yong Beom , Lee Woo Yong
Published: June 2014

Purpose: The epithelial-mesenchymal transition (EMT) is known to be associated with tumor progression, invasion and metastasis in colorectal cancer (CRC). Materials and Methods: Tissue samples obtained from 409 patients with stage III CRC treated from 2006 to 2007 were examined by immunohistochemistry to reveal the expression levels of E-cadherin, fibronectin, vimentin and α-smooth muscle actin (SMA). Results: Among the 409 patients, 402 cases (98.3%) showed positive E-cadherin expression. Positive E-cadherin expression was associated with well or moderately differentiated cell types and a stable microsatellite status. In multivariate analysis, a preoperative carcinoembryonic antigen level >5 ng/ml (p = 0.021), advanced N stage (p = 0.017), positive vascular invasion (p = 0.048), positive perineural invasion (p = 0.002) and negative E-cadherin expression (p = 0.002, relative risk = 5.098, 95% CI = 1.801-14.430) were poor prognostic factors affecting disease-free survival. The declining E-cadherin expression was associated with a poor outcome in terms of overall survival in univariate (p = 0.016) but not in multivariate analyses (p = 0.303, relative risk = 1.984, 95% CI = 0.539-7.296). Fibronectin, vimentin and α-SMA were of no prognostic value in this study. Conclusion: The expression pattern of EMT markers in stage III CRC suggests that declining E-cadherin expression is a possible immunohistochemical predictor of patient prognosis.
Combined Therapy with Insulin and Growth Hormone in 17 Patients with Type-1 Diabetes and Growth Disorders
Authors: Zucchini Stefano , Iafusco Dario , Vannelli Silvia , Rabbone Ivana , Salzano Giuseppina , Pozzobon Gabriella , Maghnie Mohamad , Cherubini Valentino , Bizzarri Carla , Bonfanti Riccardo , D'Annunzio Giuseppe , Lenzi Lorenzo , Maggio Maria Cristina , Marigliano Marco , Scaramuzza Andrea , Tumini Stefano , Iughetti Lorenzo
Published: June 2014

Background/Aim: Combined growth hormone (GH) and insulin therapy is rarely prescribed by pediatric endocrinologists. We investigated the attitude of Italian physicians to prescribing that therapy in the case of short stature and type-1 diabetes (T1DM). Methods: A questionnaire was sent and if a patient was identified, data on growth and diabetes management were collected. Results: Data from 42 centers (84%) were obtained. Of these, 29 centers reported that the use of combined therapy was usually avoided. A total of 17 patients were treated in 13 centers (GH was started before T1DM onset in 9 patients and after the onset of T1DM in 8). Height SDS patterns during GH therapy in the 11 patients affected by GH deficiency ranged from -0.3 to +3.1 SDS. In the 8 diabetic patients in whom GH was added subsequently, mean insulin dose increased during the first 6 months of therapy from 0.7 ± 0.2 to 1.0 ± 0.2 U/kg (p = 0.004). HbA1c was unchanged during the first 6 months of combined therapy. Conclusions: Most Italian physicians do not consider prescribing the combined GH-insulin therapy in diabetic children with growth problems. However, the results of the 17 patients identified would confirm that the combined therapy was feasible and only caused mild insulin resistance. GH therapy was effective in promoting growth in most patients and did not affect diabetes metabolic control.
Impact of Chronic Kidney Disease on Myocardial Blood Flow Regulation in Dogs
Authors: Kingma Jr. John G. , Simard Denys , Voisine Pierre , Rouleau Jacques R.
Published: June 2014

Background/Aims: Chronic kidney disease (CKD) increases cardiovascular risk possibly due to coronary microvessel dysfunction and impaired myocardial flow reserve. This study investigated the effects of CKD on the regulation and transmural distribution of myocardial blood flow along with oxygen demand during intravenous dobutamine-induced increases in cardiac work. Methods: CKD was produced in dogs by a two-stage subtotal nephrectomy (kidney ablation-infarction model). Serum creatinine and blood urea nitrogen were evaluated during the development of CKD along with systemic blood pressure (tail-cuff plethysmography). After 5 weeks, the CKD dogs were staged according to the International Renal Interest Society staging system; all dogs were anesthetized and surgically prepared for blood flow studies. Data analyses were performed between sham control (CTR) and stage 1 and 2 CKD dogs. Results: At baseline, myocardial blood flow and diastolic aortic pressure were similar for all groups. During intravenous dobutamine, myocardial blood flow was markedly higher than CTR even though hematocrit levels declined with the severity of CKD. In the CTR dogs, myocardial blood flow increased in direct relation to cardiac work. However, in the CKD dogs (stage 1 and 2), maximum blood flow was achieved with low-dose dobutamine, indicating that coronary autoregulation is more readily exhausted with minimal increases in cardiac work during CKD. Conclusion: We report that CKD markedly impairs coronary vascular reserve and myocardial blood flow regulation which could contribute to greater cardiovascular risk and poor clinical outcomes in CKD patients.
Physical Activity, Weight Status, Diabetes and Dementia: A 34-Year Follow-Up of the Population Study of Women in Gothenburg
Authors: Mehlig Kirsten , Skoog Ingmar , Waern Margda , Miao Jonasson Junmei , Lapidus Leif , Björkelund Cecilia , Östling Svante , Lissner Lauren
Published: June 2014

Background: There is evidence of a synergistic interaction between obesity and sedentary lifestyle with respect to diabetes. Although diabetes is a known risk factor for dementia, it is unclear if both diseases have common aetiologies. Methods: A community-based sample of 1,448 Swedish women, aged 38-60 years and free of diabetes and dementia in 1968, was followed by means of up to 5 examinations spread over 34 years. 9.6% of all women developed diabetes and 11.4% developed dementia (over 40,000 person-years of follow-up for each disease). Cox proportional hazard regression was used to assess the influence of selected risk factors on both diseases, and the relation between diabetes and dementia. Results: Comparing risk factors for incident diabetes and dementia, both diseases showed a synergistic association with obesity combined with a low level of leisure time physical activity [hazard ratio (HR) for interaction = 2.7, 95% confidence interval (CI) = 1.2-6.3 for diabetes and HR = 3.3, 95% CI = 1.1-9.9 for dementia]. Development of diabetes doubled the risk for subsequent dementia (HR = 2.2, 95% CI = 1.1-4.4), which was slightly reduced upon adjustment for common risk factors. Conclusions: Shared risk factors suggest a similar aetiology for diabetes and dementia and partially explain the association between diseases.
Cetuximab in Metastatic Squamous Cell Cancer of the Skin: A Swiss Case Series
Authors: Conen Katrin L. , Fischer Natalie , Hofbauer Günther F.L. , Shafaeddin-Schreve Bahar , Winterhalder Ralph , Rochlitz Christoph , Zippelius Alfred
Published: June 2014

Background: There is current evidence that non-melanoma skin cancers can be successfully treated with cetuximab. Objective: To evaluate the use and efficacy of cetuximab (with or without radiotherapy) in a series of previously treated patients with metastatic squamous cell cancer of the skin (SCCS) in Switzerland. Methods: We performed a retrospective analysis of six patients from four centers. Endpoints were disease control rates (DCRs) at 4-8 weeks, 12-14 weeks and 20-36 weeks of treatment. Treatment-related toxicity was evaluated additionally. Results: A median of 14 cycles of cetuximab were applied. DCR was 67% at 4-8 weeks, 50% at 12-14 weeks and 33% at 20-36 weeks. In 4-8 weeks responders, mean relapse-free time was 12 ± 6.2 months and mean overall survival was 25 ± 16.2 months. Grade I-III acne-like rash developed around week 3 of treatment in 83%. Conclusions: Cetuximab treatment in patients with metastatic SCCS achieved an overall DCR of 67% at 4-8 weeks of treatment. This study underlines the current evidence that SCCS can be successfully treated with cetuximab.
Regulation of crp Gene Expression by the Catabolite Repressor/Activator, Cra, in Escherichia coli
Authors: Zhang Zhongge , Aboulwafa Mohammad , Saier Milton H.
Published: June 2014

Growth of E. coli on several carbon sources is dependent on the catabolite repressor/activator (Cra) protein although a Cra consensus DNA-binding site is not present in the control regions of the relevant catabolic operons. We show that Cra regulates growth by activating expression of the crp gene. It thereby mediates catabolite repression of catabolic operons by an indirect mechanism.
New Inhaler Devices - The Good, the Bad and the Ugly
Authors: Lavorini Federico , Fontana Giovanni A. , Usmani Omar S.
Published: June 2014

Drug delivery to the lungs is an effective way of targeting inhaled therapeutic aerosols and treating obstructive airway diseases, such as asthma and chronic obstructive pulmonary disease (COPD). In the past 10 years, several new drugs for the management of asthma and COPD have been marketed and more are under development. These new therapeutic respiratory drugs have been furthered by innovations in all categories of pulmonary drug delivery systems to ensure optimal aerosolisation performance, consistency in efficacy and satisfactory patient adherence. In this review, we discuss the technological advances and innovations in recent inhaler devices and the evolving roles of pressurised metered-dose inhalers, dry powder inhalers and nebulisers, as well as their impact on patient adherence to treatment.
Hemostatic Function and Transfusion Efficacy of Apheresis Platelet Concentrates Treated with Gamma Irradiation in Use for Thrombocytopenic Patients
Authors: Zhu Mei , Xu Wei , Wang Bao-Long , Su Hong
Published: June 2014

Background: During the transfusion of blood components, the transfer of allogeneic donor white blood cells (WBCs) can mediate transfusion-associated graft-versus-host disease (TA-GVHD). To minimize the reaction, exposure of blood products to gamma irradiation is currently the standard of care. The aim of our study was to evaluate and compare hemostatic function, transfusion efficacy, and safety of gamma-irradiated single-donor apheresis platelet concentrates (PCs) and of conventional non-irradiated PCs in patients with chemotherapy-induced thrombocytopenia. Methods: 20 double-dose single-donor leukoreduced PCs were split in two identical units; one was gamma-irradiated with 25 Gy (study arm A) and the other remains non-irradiated (study arm B). Both units were stored under equal conditions. Hematologic patients were randomly assigned to receive gamma-irradiated or conventional non-irradiated PCs. Hemostatic function was evaluated by thrombelastography (TEG). TEG measurements were taken pre transfusion and 1 and 24 h post transfusion. TEG profiles were measured, noting the time to initiate clotting (R), the angle of clot formation (α), and the maximum amplitude (clot strength (MA)). Whole blood samples were collected from these thrombocytopenic patients at 1 and 24 h for PLT count increments (CIs) and corrected count increments (CCIs) with assessments of transfusion efficacy. Time to next PLT transfusion, transfusion requirement of RBCs, active bleeding, and adverse events (AEs), were analyzed. Results: No differences could be found in hemostatic function parameters (MA, R, and α) between study arms A and B (all p values > 0.096) pre transfusion as well as 1 and 24 h post transfusion. No differences between study arms A and B were observed for mean (± standard deviation (SD)) 1-hour CCI (12.83 ± 6.33 vs. 11.59 ± 5.97) and 24-hour CCI (6.56 ± 4.10 vs. 5.76 ± 4.05). Mean 1-hour CI and 24-hour CI were not significantly different in both study arms (p = 0.254 and p = 0.242 respectively). Median time to the next PC transfusion after study PC was not significantly different between groups: (2.4 vs. 2.2 days, p = 0.767). No differences could be found in transfusion requirement of red blood cells (p = 0.744) between both study arms. There were also no regarding bleeding, adverse events, and acute transfusion reaction(s). Conclusions: This study confirms safety of gamma-irradiated PCs for treatment thrombocytopenia. Hemostatic function, transfusion efficacy, bleeding, and safety of single-donor apheresis PCs treated with gamma irradiation versus untreated control PCs are comparable.
Prostaglandin I
2
and Prostaglandin E
2
Modulate Human Intrarenal Artery Contractility Through Prostaglandin E2-EP4, Prostacyclin-IP, and Thromboxane A2-TP Receptors
Authors: Eskildsen Morten P. , Hansen Pernille B.L. , Stubbe Jane , Toft Anja , Walter Steen , Marcussen Niels , Rasmussen Lars M. , Vanhoutte Paul M. , Jensen Boye L.
Published: June 2014

Cyclooxygenase inhibitors decrease renal blood flow in settings with decreased effective circulating volume. The present study examined the hypothesis that prostaglandins, prostaglandin E
2
(PGE
2
) and prostacyclin (PGI
2
), induce relaxation of human intrarenal arteries through PGE
2
-EP and PGI
2
-IP receptors. Intrarenal arteries were microdissected from human nephrectomy samples (n=53, median diameter ≈362 μm, 88% viable, 76% relaxed in response to acetylcholine). Rings were suspended in myographs to record force development. In vessels with K
+
-induced tension (EC
70
: –log [mol/L]=1.36±0.03), PGE
2
and PGI
2
induced concentration-dependent relaxation (–log EC
50
: PGE
2
=7.1±0.3 and PGI
2
=7.7). The response to PGE
2
displayed endothelium dependence and desensitization. Relaxation by PGE
2
was mimicked by an EP4 receptor agonist (CAY10598, EC
50
=6.7±0.2). The relaxation after PGI
2
was abolished by an IP receptor antagonist (BR5064, 10
–8
mol/L). Pretreatment of quiescent arteries with PGE
2
for 5 minutes (10
–6
mol/L) led to a significant right shift of the concentration–response to norepinephrine (EC
50
from 6.6±0.1–5.9±0.1). In intrarenal arteries with K
+
-induced tone, PGE
2
and PGI
2
at 10
–5
mol/L elicited increased tension. This was abolished by thromboxane receptor (TP) antagonist (S18886, 10
–6
mol/L). A TP agonist (U46619, n=6) evoked tension (EC
50
=8.1±0.2) that was inhibited by S18886. Polymerase chain reaction and immunoblotting showed EP4, IP, and TP receptors in intrarenal arteries. In conclusion, PGE
2
and PGI
2
may protect renal perfusion by activating cognate IP and EP4 receptors associated with smooth muscle cells and endothelium in human intrarenal arteries and contribute to increased renal vascular resistance at high pathological concentrations mediated by noncognate TP receptor.
The ATP-Sensitive Potassium Channel Subunit, Kir6.1, in Vascular Smooth Muscle Plays a Major Role in Blood Pressure Control
Authors: Aziz Qadeer , Thomas Alison M. , Gomes John , Ang Richard , Sones William R. , Li Yiwen , Ng Keat-Eng , Gee Lorna , Tinker Andrew
Published: June 2014

ATP-sensitive potassium channels (K
ATP
) regulate a range of biological activities by coupling membrane excitability to the cellular metabolic state. In particular, it has been proposed that K
ATP
channels and specifically, the channel subunits Kir6.1 and SUR2B, play an important role in the regulation of vascular tone. However, recent experiments have suggested that K
ATP
channels outside the vascular smooth muscle compartment are the key determinant of the observed behavior. Thus, we address the importance of the vascular smooth muscle K
ATP
channel, using a novel murine model in which it is possible to conditionally delete the Kir6.1 subunit. Using a combination of molecular, electrophysiological, in vitro, and in vivo techniques, we confirmed the absence of Kir6.1 and K
ATP
currents and responses specifically in smooth muscle. Mice with conditional deletion of Kir6.1 showed no obvious arrhythmic phenotype even after provocation with ergonovine. However, these mice were hypertensive and vascular smooth muscle cells failed to respond to vasodilators in a normal fashion. Thus, Kir6.1 underlies the vascular smooth muscle K
ATP
channel and has a key role in vascular reactivity and blood pressure control.
Plasma Levels of Nitric Oxide Metabolites Are Markedly Reduced in Normotensive Men With Electrocardiographically Determined Left Ventricular Hypertrophy
Authors: Kamezaki Fumihiko , Tsutsui Masato , Takahashi Masao , Sonoda Shinjo , Kubo Tatsuhiko , Fujino Yoshihisa , Adachi Tetsuo , Abe Haruhiko , Takeuchi Masaaki , Mayumi Toshihiko , Otsuji Yutaka
Published: June 2014

Recent studies have revealed that electrocardiographically determined left ventricular hypertrophy (ECG-LVH) is a risk factor for cardiovascular death not only in hypertensive patients but also in normotensive subjects. However, the underlying mechanisms remain to be elucidated. In this study, we tested our hypothesis that normotensive subjects with ECG-LVH have reduced nitric oxide production. A total of 840 Japanese male workers were enrolled, and 579 eligible subjects were studied. ECG-LVH was assessed according to the Sokolow–Lyon voltage criteria and the Cornell voltage–duration product. The median level of plasma NOx (nitrite plus nitrate), a marker of systemic nitric oxide production, was markedly lower in the normotensive subjects with ECG-LVH (n=73) than in those without (n=506), and the clinical characteristics were significantly different between the 2 groups (each
P
<0.05). Importantly, a one-to-one propensity score matching analysis showed similar markedly lower median plasma NOx level in the normotensive subjects with ECG-LVH compared with that observed in the matched normotensive subjects without ECG-LVH (
P
<0.05). Furthermore, the tertiles of the plasma NOx levels were inversely correlated with the prevalence and severity of ECG-LVH (both
P
<0.05). The lower plasma NOx levels were associated with significantly higher plasma 8-isoprostane levels, a marker of systemic lipid peroxidation (
P
<0.05). These results provide the first evidence that normotensive subjects with ECG-LVH exhibit defective nitric oxide production, along with increased oxidative stress. Our findings may thus explain, at least in part, a potential mechanism underlying the increased risk of cardiovascular death in normotensive individuals with ECG-LVH.
Female Spontaneously Hypertensive Rats Have a Compensatory Increase in Renal Regulatory T Cells in Response to Elevations in Blood Pressure
Authors: Tipton Ashlee J. , Baban Babak , Sullivan Jennifer C.
Published: June 2014

Female spontaneously hypertensive rats (SHR) have more regulatory T cells (Tregs) in their kidneys than males. The goal of this study was to determine the impact of blood pressure (BP) on the renal immune profile. We hypothesize that increases in BP promote a proinflammatory renal T cell and cytokine profile in SHR, although females will have greater hormone-dependent increases in Tregs and males will have greater increases in Th17 cells. Renal T cell and cytokine profiles were assessed in male and female Wistar-Kyoto rats and male and female SHR treated with vehicle or hydrochlorothiazide and reserpine (HCTZ) from 6 to 12 (6-HCTZ) or 11 to 13 weeks of age (2-HCTZ). Regardless of sex, SHR had a more proinflammatory renal immune profile than Wistar-Kyoto rats. 6-HCTZ attenuated age-related increases in BP and 2-HCTZ reversed hypertension compared with vehicle-treated SHR. Neither 6-HCTZ nor 2-HCTZ altered CD3
+
, CD4
+
, or CD8
+
T cells in either sex. Both treatments decreased Tregs only in female SHR abolishing sex differences in Tregs. 6-HCTZ has no impact on Th17 cells in either sex and 2-HCTZ had a minimal impact on renal Th17 cells. To further assess mechanisms mediating sex differences in the renal immune profile, male and female SHR were gonadectomized to determine the impact of sex hormones. Gonadectomy increased proinflammatory markers in both sexes, suggesting that both male and female sex hormones are anti-inflammatory. In conclusion, BP contributes to sex differences in the renal T-cell profile of SHR; female SHR increase renal Tregs in response to increases in BP.
Interference With Peroxisome Proliferator-Activated Receptor-γ in Vascular Smooth Muscle Causes Baroreflex Impairment and Autonomic Dysfunction
Authors: Borges Giulianna R. , Morgan Donald A. , Ketsawatsomkron Pimonrat , Mickle Aaron D. , Thompson Anthony P. , Cassell Martin D. , Mohapatra Durga P. , Rahmouni Kamal , Sigmund Curt D.
Published: June 2014

S-P467L mice expressing dominant negative peroxisome proliferator-activated receptor-γ selectively in vascular smooth muscle exhibit impaired vasodilation, augmented vasoconstriction, hypertension, and tachycardia. We hypothesized that tachycardia in S-P467L mice is a result of baroreflex dysfunction. S-P467L mice displayed increased sympathetic traffic to the heart and decreased baroreflex gain and effectiveness. Carotid arteries exhibited inward remodeling but no changes in distensibility or stress/strain. Aortic depressor nerve activity in response to increased arterial pressure was blunted in S-P467L mice. However, the arterial pressure and heart rate responses to aortic depressor nerve stimulation were unaltered in S-P467L mice, suggesting that the central and efferent limbs of the baroreflex arc remain intact. There was no transgene expression in nodose ganglion and no change in expression of the acid-sensing ion channel-2 or -3 in nodose ganglion. There was a trend toward decreased expression of transient receptor potential vanilloid-1 receptor mRNA in nodose ganglion, but no difference in the immunochemical staining of transient receptor potential vanilloid-1 receptor in the termination area of the left aortic depressor nerve in S-P467L mice. Although there was no difference in the maximal calcium response to capsaicin in cultured nodose neurons from S-P467L mice, there was decreased desensitization of transient receptor potential vanilloid-1 receptor channels. In conclusion, S-P467L mice exhibit baroreflex dysfunction because of a defect in the afferent limb of the baroreflex arc caused by impaired vascular function, altered vascular structure, or compromised neurovascular coupling. These findings implicate vascular smooth muscle peroxisome proliferator activated receptor-γ as a critical determinant of neurovascular signaling.
Healthy Lifestyle Factors and Risk of Cardiovascular Events and Mortality in Treatment-Resistant Hypertension
Authors: Diaz Keith M. , Booth John N. , Calhoun David A. , Irvin Marguerite R. , Howard George , Safford Monika M. , Muntner Paul , Shimbo Daichi
Published: June 2014

Few data exist on whether healthy lifestyle factors are associated with better prognosis among individuals with apparent treatment-resistant hypertension, a high-risk phenotype of hypertension. The purpose of this study was to assess the association of healthy lifestyle factors with cardiovascular events, all-cause mortality, and cardiovascular mortality among individuals with apparent treatment-resistant hypertension. We studied participants (n=2043) from the population-based Reasons for Geographic and Racial Differences in Stroke (REGARDS) study with apparent treatment-resistant hypertension (blood pressure ≥140/90 mm Hg despite the use of 3 antihypertensive medication classes or the use of ≥4 classes of antihypertensive medication regardless of blood pressure control). Six healthy lifestyle factors adapted from guidelines for the management of hypertension (normal waist circumference, physical activity ≥4 times/week, nonsmoking, moderate alcohol consumption, high Dietary Approaches to Stop Hypertension diet score, and low sodium-to-potassium intake ratio) were examined. A greater number of healthy lifestyle factors were associated with lower risk for cardiovascular events (n=360) during a mean follow-up of 4.5 years. Multivariable-adjusted hazard ratios [HR (95% confidence interval)] for cardiovascular events comparing individuals with 2, 3, and 4 to 6 versus 0 to 1 healthy lifestyle factors were 0.91 (0.68–1.21), 0.80 (0.57–1.14), and 0.63 (0.41–0.95), respectively (
P
-trend=0.020). Physical activity and nonsmoking were individual healthy lifestyle factors significantly associated with lower risk for cardiovascular events. Similar associations were observed between healthy lifestyle factors and risk for all-cause and cardiovascular mortality. In conclusion, healthy lifestyle factors, particularly physical activity and nonsmoking, are associated with a lower risk for cardiovascular events and mortality among individuals with apparent treatment-resistant hypertension.
Manuel I of Portugal and the End of the Toleration of Islam in Castile: Marriage Diplomacy, Propaganda, and Portuguese Imperialism in Renaissance Europe, 1495-1505
Authors: Soyer François
Published: June 2014

In 1505, King Manuel I of Portugal (1495-1521) ordered the public printing of a letter officially addressed to Pope Julius II. In the letter, the Portuguese King defended his role as a champion of Christendom and scourge of Islam in the Indian Ocean. The most remarkable claim made by Manuel in this letter was that he was directly involved in persuading the Catholic monarchs of Spain Isabel of Castile and Fernando of Aragón to put an end to the toleration of Islam in Castile in 1501. This article focuses on this claim and whether or not it can merely be dismissed as the rhetoric of bombastic propaganda. It analyzes Luso-Spanish relations between 1495 and 1505 and highlights documentary evidence proving that Manuel did indeed put pressure on his Spanish neighbors to abolish the toleration of Islam during the tortuous negotiations surrounding his marriage to the Spanish princess Maria in 1501. Beyond assessing the historical significance of the letter, this article highlights the intricate connections between Portuguese imperial geopolitics and Iberian dynastic politics during this crucial period in the history of both the Spanish and Portuguese monarchies.
Spanish Forest Reconnaissance and the Search for Shipbuilding Timber in an Era of Naval Resurgence, 1737-1739
Authors: Wing John T.
Published: June 2014

Between 1737 and 1739, Spanish naval officers conducted reconnaissance missions in nearly all forests within accessible range of naval shipyards to determine their suitability for shipbuilding. Spain’s top naval minister, the Marqués de la Ensenada, oversaw the collection of these reports, which were meant to aid broader state-enhancement reforms. While the practice of Spanish naval forest reconnaissance was not new in this period, the scale and urgency was unprecedented and set in motion a new era of territorialization within Spain, strengthening the crown’s control of natural resources. Crown management of forests, based on more reliable knowledge of their quality, locations, and accessibility, was integral during a period of naval resurgence in the mid-eighteenth century, but remains poorly studied. The article analyzes the motivations, strategies, methods, and findings of numerous forest reconnaissance missions from across Spain during this period.
The divergence of small mammals in Xinjiang, China, as revealed by phylogentic analyses of COI and Cytb
Authors: Yin Yanqiang , Jiang Wei , Zhang Zhe , Li Yan , Twenke Bayaerta , Turghan Mardan , Yang Weikang , Liu Bin
Published: June 2014

Changes in the palaeoenvironment and paleoclimate expedite the process of evolutionary divergence in animals. The evolutionary events of some small mammals distributed in Xinjiang Arid Region remain ambiguous. Thus, it is necessary to predict their evolutionary histories based on divergence estimates. Some museum specimens were involved in this analysis because of sampling limitation for threatened species in the arid region. A related problem is that some mutilated specimens without complete taxonomic data made it difficult to directly analyze species divergence. Here, sequences of cytochrome c oxydase I were used to identify museum specimens and combined with cytochrome b to estimate the recent divergence of extant small mammals constrained with eight fossil calibrations. The results showed that the massive species differentiation emerged during the Middle and Late Miocene periods. We inferred that differentiation of these small mammals might be associated with the retreat of the Tethys Sea from the Tarim Basin around the Eocene-Oligocene boundary and the global climate fluctuations during the Miocene period. Furthermore, the aridification and changes in the Taklimakan and Gurbantunggut Deserts might have driven the diversification of intraspecies and the emergence of cryptic species since the Late Pleistocene.
Home range and activity patterns of Conepatus semistriatus (Carnivora, Mephitidae) in Emas National Park, Brazil
Authors: Cavalcanti Gitana Nunes , Alfaro-Alvarado Luis Diego , Rodrigues Flávio Henrique Guimarães
Published: June 2014

Skunks (Mephitidae) have not been well studied throughout the Neotropics. In Brazil there is a general lack of data on the ecology, behavior, distribution, systematics, morphology and biogeographic patterns of the two species occurring in the country (Conepatus semistriatus and C. chinga). The focus of this study was on understanding the home range and activity patterns of C. semistriatus. Field research was conducted in the Emas National Park, where three skunks with radio-collars were located on 157 separate occasions. The observed patterns of activity indicate that the species is predominantly nocturnal, with a great expenditure of time on foraging. Temperature had a direct influence on the animal’s behavior, but there was no apparent influence of light on activity patterns. Average home range areas were 1.39 ± 0.87 km2 (Minimum Convex Polygon method) and 0.69 ± 0.25 km2 (Local Convex Hull method). There was high home range overlap between individuals, 0.27 km2 based on the Minimum Convex Polygon method, at sites with easy access to resources.
A reappraisal of the existence of an avian pyramidal tract, a review
Authors: Dubbeldam Jacob L.
Published: June 2014

This communication presents a concise overview of reports in the literature concerning the occurrence of extratelencephalic fibre tracts in birds and the comparability of these tracts with the mammalian pyramidal tract. Emphasis is on the intratelencephalic organization, in particular that of the intratelencephalic sensorimotor circuits processing information from all important types of sense organs. It is suggested that two descending tracts, the occipitomesencephalic tract and the basal tractus superficialis medialis in birds have the same role in guiding behaviour as the pyramidal pathway in mammals. However, the differences in origin, trajectory and targets suggest that two independent systems may have developed in birds. One of these, the basal tractus superficialis medialis, represents the homologue of the pyramidal tract. It is suggested that the occipitomesencephalic tract is a specific feature of birds that has developed during the evolution from the early dinosaurs to birds. This suggestion follows from recent observations on the evolution of birds.
Modeling Cooperative Peacekeeping
Authors: Brosig Malte , Motsamai Dimpho
Published: June 2014

Analyses of overlapping international organizations (ios) in security governance has gradually reached mainstream research. However, theory building is still in its infancy. Thus, this article aims to substantiate theory building by applying exchange theory to io interplay. Empirically, the article focuses on the African peace and security regime, which constitutes an interlocking system of global and regional governance, integrating both African and non-African ios. The article argues that inter-institutional cooperation is primarily driven by a functional logic of resource complementarity, compelled by resource scarcity. However, in practice, ios do not easily complement each other. The article finds that divergence of security concepts; the absence of institutional match and the strife for institutional autonomy can hamper cooperation significantly.
New fossil Praeaulacinae wasps (Insect: Hymenoptera: Evanioidea: Praeaulacidae) from the Middle Jurassic of China
Authors: LI LONGFENG , SHIH CHUNGKUN , REN DONG
Published: June 2014

A new genus with a new species, Archaulacus probus gen. et sp. nov., and two new species, Praeaulacus subrhombeus sp. nov., P. tenellus sp. nov., belonging to the subfamily Praeaulacinae (Praeaulacidae) are described and illustrated. The specimens were collected from the Middle Jurassic of Jiulongshan Formation at Daohugou in Inner Mongolia, China. Archaulacus gen. nov. differs from other genera of Praeaulacinae in having the first abscissa of Rs of the fore wing subvertical to R and 2m-cu slightly basad of 2r-m. This is the first time that these characters are reported for the Praeaulacinae. Based on new information provided by the new species, an updated key to the known species of Praeaulacus is provided.
Flea weevils of the genus Megorchestes Kojima (Coleoptera, Curculionidae, Curculioninae, Rhamphini), with description of a second species from India
Authors: AYRI SHALOO , KOJIMA HIROAKI , RAMAMURTHY V. V.
Published: June 2014

A second species of Megorchestes Kojima, M. deccanensis sp. nov., is described from India and a key to the two species is provided.
The Potential Predictability of Precipitation Occurrence, Intensity, and Seasonal Totals over the Continental United States
Authors: Short Gianotti Daniel J. , Anderson Bruce T. , Salvucci Guido D.
Published: June 2014

Using weather station data, the parameters of a stationary stochastic weather model (SSWM) for daily precipitation over the contiguous United States are estimated. By construct, the model exactly captures the variance component of seasonal precipitation characteristics (intensity, occurrence, and total amount) arising from high-frequency variance. By comparing the variance of the lower-frequency accumulations (on the order of months) between the SSWM and the original measurements, potential predictability (PP) is estimated. Decomposing the variability into contributions from occurrence and intensity allows one to establish two contributing sources of total PP. Aggregated occurrence is found to have higher PP than either intensity or the seasonal total precipitation, and occurrence and intensity are found to interfere destructively when convolved into seasonal totals. It is recommended that efforts aimed at forecasting seasonal precipitation or attributing climate variability to particular processes should analyze occurrence and intensity separately to maximize signal-to-noise ratios. Significant geographical and seasonal variations exist in all PP components.
A Weibull Approach for Improving Climate Model Projections of Tropical Cyclone Wind-Speed Distributions
Authors: Tye Mari R. , Stephenson David B. , Holland Greg J. , Katz Richard W.
Published: June 2014

Reliable estimates of future changes in extreme weather phenomena, such as tropical cyclone maximum wind speeds, are critical for climate change impact assessments and the development of appropriate adaptation strategies. However, global and regional climate model outputs are often too coarse for direct use in these applications, with variables such as wind speed having truncated probability distributions compared to those of observations. This poses two problems: How can model-simulated variables best be adjusted to make them more realistic? And how can such adjustments be used to make more reliable predictions of future changes in their distribution?

This study investigates North Atlantic tropical cyclone maximum wind speeds from observations (1950–2010) and regional climate model simulations (1995–2005 and 2045–55 at 12- and 36-km spatial resolutions). The wind speed distributions in these datasets are well represented by the Weibull distribution, albeit with different scale and shape parameters.

A power-law transfer function is used to recalibrate the Weibull variables and obtain future projections of wind speeds. Two different strategies, bias correction and change factor, are tested by using 36-km model data to predict future 12-km model data (pseudo-observations). The strategies are also applied to the observations to obtain likely predictions of the future distributions of wind speeds. The strategies yield similar predictions of likely changes in the fraction of events within Saffir–Simpson categories—for example, an increase from 21% (1995–2005) to 27%–37% (2045–55) for category 3 or above events and an increase from 1.6% (1995–2005) to 2.8%–9.8% (2045–55) for category 5 events.
The Impact of the Tracer Size and the Temporal Gap between Images in the Extraction of Atmospheric Motion Vectors
Authors: García-Pereda Javier , Borde Régis
Published: June 2014

The goal of this paper is to show the impact of the tracer size and the temporal gap between images in atmospheric motion vector (AMV) extraction schemes. A test has been performed using NWC SAF/High Resolutions Winds AMV software for different configurations with a tracer size varying between 8 × 8 and 40 × 40 pixels and a temporal gap between images varying between 5 and 90 min. AMVs have been extracted for four different MSG/SEVIRI channels (HRVIS, VIS0.8, WV6.2, and IR10.8) over the European and Mediterranean area for a 6-month period (January–June 2010). The AMV performances have been tested against radiosonde winds and ECMWF model analysis winds.

The results show a small impact of the tracer size on the number of valid AMVs, which is, however, more significant for clear air AMVs, and a significant impact of the temporal gap between images. The largest number of valid AMVs has been found in general for a temporal gap of 5 min for the 1-km pixel scale and for a temporal gap of 10 min for the 3-km pixel scale. Results also show a decrease of the mean AMV speed and the normalized BIAS (NBIAS) with larger tracer sizes, and a relatively small impact of the temporal gap on these parameters. Finally, the results show minimum values of the normalized root-mean-square vector difference (NRMSVD) for intermediate temporal gaps between 15 and 30 min with a relatively small impact of the tracer size on this parameter.
The Three-Dimensional Morphology of Simulated and Observed Convective Storms over Southern England
Authors: Stein Thorwald H. M. , Hogan Robin J. , Hanley Kirsty E. , Nicol John C. , Lean Humphrey W. , Plant Robert S. , Clark Peter A. , Halliwell Carol E.
Published: June 2014

A set of high-resolution radar observations of convective storms has been collected to evaluate such storms in the Met Office Unified Model during the Dynamical and Microphysical Evolution of Convective Storms (DYMECS) project. The 3-GHz Chilbolton Advanced Meteorological Radar was set up with a scan-scheduling algorithm to automatically track convective storms identified in real time from the operational rainfall radar network. More than 1000 storm observations gathered over 15 days in 2011 and 2012 are used to evaluate the model under various synoptic conditions supporting convection. In terms of the detailed three-dimensional morphology, storms in the 1500-m grid length simulations are shown to produce horizontal structures a factor of 1.5–2 wider compared to radar observations. A set of nested model runs at grid lengths down to 100 m show that the models converge in terms of storm width, but the storm structures in the simulations with the smallest grid lengths are too narrow and too intense compared to the radar observations. The modeled storms were surrounded by a region of drizzle without ice reflectivities above 0 dBZ aloft, which was related to the dominance of ice crystals and was improved by allowing only aggregates as an ice particle habit. Simulations with graupel outperformed the standard configuration for heavy-rain profiles, but the storm structures were a factor of 2 too wide and the convective cores 2 km too deep.
Precipitation Calibration Based on the Frequency-Matching Method
Authors: Zhu Yuejian , Luo Yan
Published: June 2014

A postprocessing technique is employed to correct model bias for precipitation fields in real time based on a comparison of the frequency distributions of observed and forecast precipitation amounts. Essentially, a calibration is made by defining an adjustment to the forecast value in such a way that the adjusted cumulative forecast distribution over a moving time window dynamically matches the corresponding observed distribution accumulated over a domain of interest, for example, the entire conterminous United States (CONUS), or different River Forecast Center (RFC) regions in the cases examined herein. In particular, the Kalman filter method is used to catch the flow dependence and bias information. Calibration is done on a pointwise basis for a specified domain. Using this unique technique, the calibration of precipitation forecasts for the National Centers for Environmental Prediction (NCEP) Global Ensemble Forecast System (GEFS) was implemented in May 2004. To further satisfy various users, a recent upgrade to the May 2004 implementation has been made for higher resolution with better analyses. From this study, it was found that this method has a positive impact on the intensity-dominated errors but has some common limitations with extreme events and dry bias elimination like other precipitation calibration methods. Overall, the frequency-matching algorithm substantially improves NCEP Global Forecast System (GFS) and GEFS systematic precipitation forecast errors (or biases) over a wide range of forecast amounts and produces more realistic precipitation patterns. Moreover, this approach improves the deterministic forecast skills measured by most verification scores through applying this method to GFS and GEFS ensemble means.
Fifty Years of Family Change
Authors: Furstenberg Frank F.
Published: June 2014

The first section of the article discusses how and why we went from a relatively undifferentiated family system in the middle of the last century to the current system of diverse family forms. Even conceding that the family system was always less simple than it now appears in hindsight, there is little doubt that we began to depart from the dominant model of the nuclear-family household in the late 1960s. I explain how change is a result of adaptation by individuals and family members to changing economic, demographic, technological, and cultural conditions. The breakdown of the gender-based division of labor was the prime mover in my view. Part two of the article thinks about family complexity in the United States as largely a product of growing stratification. I show how family formation processes associated with low human capital produces complexity over time in family systems, a condition that may be amplified by growing levels of inequality. The last part of the article briefly examines complexity in a changing global context. I raise the question of how complexity varies among economically developed nations with different family formation practices and varying levels of inequality.