bluuebunny/crossref_metadata_2025 huggingface dataset:
Fast Cylindrical Fitting Method Using Point Cloud’s Normals Estimation
Authors: Wu Yunlong , Zhang Qing , Zhang Shuxuan
Published: December 2018

Cylindrical fitting is an essential step in Large Process Pipeline’s measurement process, and precision of initial values of cylindrical fitting is a key element in getting a correct fitting result. In order to get well initial values, covariance matrixes of all points in cylinder’s three-dimensional laser scanning point cloud should be firstly established to estimate normals of all points, and then cylinder’s axis vector can be calculated by using least squares method. Secondly, remaining parameters’ initial values of the cylinder can be got by coordinate transformation. Finally, Levenberg-Marquardt algorithm is used in iterative optimization process to get fitting result by using the above values as initial values. Experiments demonstrate that this method can get precise initial values of cylindrical fitting and improve the accuracy and speed of cylindrical fitting.
Dynamics of Tumor and Immune Responses during Immune Checkpoint Blockade in Non–Small Cell Lung Cancer
Authors: Anagnostou Valsamo , Forde Patrick M. , White James R. , Niknafs Noushin , Hruban Carolyn , Naidoo Jarushka , Marrone Kristen , Sivakumar I.K. Ashok , Bruhm Daniel C. , Rosner Samuel , Phallen Jillian , Leal Alessandro , Adleff Vilmos , Smith Kellie N. , Cottrell Tricia R. , Rhymee Lamia , Palsgrove Doreen N. , Hann Christine L. , Levy Benjamin , Feliciano Josephine , Georgiades Christos , Verde Franco , Illei Peter , Li Qing Kay , Gabrielson Edward , Brock Malcolm V. , Isbell James M. , Sauter Jennifer L. , Taube Janis , Scharpf Robert B. , Karchin Rachel , Pardoll Drew M. , Chaft Jamie E. , Hellmann Matthew D. , Brahmer Julie R. , Velculescu Victor E.
Published: December 2018

Despite the initial successes of immunotherapy, there is an urgent clinical need for molecular assays that identify patients more likely to respond. Here, we report that ultrasensitive measures of circulating tumor DNA (ctDNA) and T-cell expansion can be used to assess responses to immune checkpoint blockade in metastatic lung cancer patients (N = 24). Patients with clinical response to therapy had a complete reduction in ctDNA levels after initiation of therapy, whereas nonresponders had no significant changes or an increase in ctDNA levels. Patients with initial response followed by acquired resistance to therapy had an initial drop followed by recrudescence in ctDNA levels. Patients without a molecular response had shorter progression-free and overall survival compared with molecular responders [5.2 vs. 14.5 and 8.4 vs. 18.7 months; HR 5.36; 95% confidence interval (CI), 1.57–18.35; P = 0.007 and HR 6.91; 95% CI, 1.37–34.97; P = 0.02, respectively], which was detected on average 8.7 weeks earlier and was more predictive of clinical benefit than CT imaging. Expansion of T cells, measured through increases of T-cell receptor productive frequencies, mirrored ctDNA reduction in response to therapy. We validated this approach in an independent cohort of patients with early-stage non–small cell lung cancer (N = 14), where the therapeutic effect was measured by pathologic assessment of residual tumor after anti-PD1 therapy. Consistent with our initial findings, early ctDNA dynamics predicted pathologic response to immune checkpoint blockade. These analyses provide an approach for rapid determination of therapeutic outcomes for patients treated with immune checkpoint inhibitors and have important implications for the development of personalized immune targeted strategies.

Significance: Rapid and sensitive detection of circulating tumor DNA dynamic changes and T-cell expansion can be used to guide immune targeted therapy for patients with lung cancer.

See related commentary by Zou and Meyerson, p. 1038
Viewing Target Distance Influences the Vestibulo-Ocular Reflex Gain when Assessed Using the Video Head Impulse Test
Authors: Castro Patricia , Sena Esteves Sara , Lerchundi Florencia , Buckwell David , Gresty Michael A. , Bronstein Adolfo M. , Arshad Qadeer
Published: December 2018

Gaze stabilization during head movements is provided by the vestibulo-ocular reflex (VOR). Clinical assessment of this reflex is performed using the video Head Impulse Test (vHIT). To date, the influence of different fixation distances on VOR gain using the vHIT has not been explored. We assessed the effect of target proximity on the horizontal VOR using the vHIT. Firstly, we assessed the VOR gain in 18 healthy subjects with 5 viewing target distances (150, 40, 30, 20, and 10 cm). The gain increased significantly as the viewing target distance decreased. A second experiment on 10 subjects was performed in darkness whilst the subjects were imagining targets at different distances. There were significant inverse relationships between gain and distance for both the real and the imaginary targets. There was a statistically significant difference between light and dark gains for the 20- and 40-cm distances, but not for the 150-cm distance. Theoretical VOR gains for different target distances were calculated and compared with those found in light and darkness. The increase in gain observed for near targets was lower than predicted by geometrical calculations, implying a physiological ceiling effect on the VOR. The VOR gain in the dark, as assessed with the vHIT, demonstrates an enhancement associated with a reduced target distance.
Impaired Consciousness in the Emergency Department
Authors: Völk Stefanie , Koedel Uwe , Pfister Hans-Walter , Schwankhart Roland , op den Winkel Mark , Mühlbauer Konstanze , Klein Matthias
Published: December 2018

Background: The approach to unconscious patients in the emergency department (ED) is difficult, often depends on local resources and interests, and workup strategies often lack standardization. One reason for this is that data on causes, management, and outcome of patients who present to the ED with sudden onset unconsciousness of unknown cause is limited. Objectives: This study was performed to analyze the causes of acute impaired consciousness in patients in an interdisciplinary ED. Methods: Here, we analyzed all patients who were admitted to the ED of a tertiary care hospital with the dominating symptom of “sudden onset unconsciousness” within 1 year (September 2014 until August 2015). Patients with a clear diagnosis at arrival that explained the altered state of consciousness or other dominating symptoms at the time of arrival were not included. Results: A total of 212 patients were analyzed. In 88% of the patients, a final diagnosis could be established in the ED. Most common causes for unconsciousness were cerebrovascular diseases (24%), infections (14%), epileptic seizures (12%), psychiatric diseases (8%), metabolic causes (7%), intoxications (7%), transient global amnesia (5%), and cardiovascular causes (4%). The diagnoses were predominantly established by physical examination in combination with computed tomography (23%) and by the results of laboratory testing (25%). In-hospital mortality was 11%, and 59% of all patients were discharged with a Glasgow Outcome Score of 2–4. Conclusions: This analysis demonstrates a large variety of etiologies in patients with unknown unconsciousness of acute onset who are admitted to an ED. As neurological diagnoses are among the most common etiologies, neurological qualification is required in the ED, and availability of diagnostics such as cerebral imaging is indispensable and recommended as an early step in a standardized clinical approach.
Um herói de duas faces – sobre as ambiguidades do Impostor Felix Krull
Authors: Frungillo Mário Luiz
Published: December 2018

O romance Confissões do Impostor Felix Krull (Bekenntnisse des Hochstaplers Felix Krull), de Thomas Mann, combina elementos do romance de formação e da novela picaresca. Essa mescla confere uma forte ambiguidade ao caráter do protagonista, que justifica suas imposturas elaborando o que poderíamos chamar de uma “teoria da permutabilidade”: numa sociedade em que os papéis sociais poderiam ser trocados sem que ninguém percebesse, a impostura deixa de ser uma transgressão para se tornar a própria regra.
Novel Model to Predict Gastrointestinal Bleeding During Left Ventricular Assist Device Support
Authors: Yin Michael Yaoyao , Ruckel Shane , Kfoury Abdallah G. , McKellar Stephen H. , Taleb Iosif , Gilbert Edward M. , Nativi-Nicolau Jose , Stehlik Josef , Reid Bruce B. , Koliopoulou Antigone , Stoddard Gregory J. , Fang James C. , Drakos Stavros G. , Selzman Craig H. , Wever-Pinzon Omar
Published: December 2018

Background:

Gastrointestinal bleeding (GIB) is a leading cause of morbidity during continuous-flow left ventricular assist device (CF-LVAD) support. GIB risk assessment could have important implications for candidate selection, informed consent, and postimplant therapeutic strategies. The aim of the study is to derive and validate a predictive model of GIB in CF-LVAD patients.

Methods and Results:

CF-LVAD recipients at the Utah Transplantation Affiliated Hospitals program between 2004 and 2017 were included. GIB associated with a decrease in hemoglobin ≥2 g/dL was the primary end point. A weighted score comprising preimplant variables independently associated with GIB was derived and internally validated. A total of 351 patients (median age, 59 years; 82% male) were included. After a median of 196 days, GIB occurred in 120 (34%) patients. Independent predictors of GIB included age >54 years, history of previous bleeding, coronary artery disease, chronic kidney disease, severe right ventricular dysfunction, mean pulmonary artery pressure <18 mm Hg, and fasting glucose >107 mg/dL. A weighted score termed Utah bleeding risk score, effectively stratified patients based on their probability of GIB: low (0–1 points) 4.8%, intermediate (2–4) 39.8%, and high risk (5–9) 83.8%. Discrimination was good in the development sample (c-index: 0.83) and after internal bootstrap validation (c-index: 0.74).

Conclusions:

The novel Utah bleeding risk score is a simple tool that can provide personalized GIB risk estimates in CF-LVAD patients. This scoring system may assist clinicians and investigators in designing tailored risk-based strategies aimed at reducing the burden posed by GIB in the individual CF-LVAD patient and healthcare systems.
Different Relationship Between Systolic Blood Pressure and Cerebral Perfusion in Subjects With and Without Hypertension
Authors: Glodzik Lidia , Rusinek Henry , Tsui Wai , Pirraglia Elizabeth , Kim Hee-Jin , Deshpande Anup , Li Yi , Storey Pippa , Randall Catherine , Chen Jingyun , Osorio Ricardo S. , Butler Tracy , Tanzi Emily , McQuillan Molly , Harvey Patrick , Williams Stephen K. , Ogedegbe Gbenga , Babb James S. , de Leon Mony J.
Published: December 2018

Although there is an increasing agreement that hypertension is associated with cerebrovascular compromise, relationships between blood pressure (BP) and cerebral blood flow are not fully understood. It is not known what BP level, and consequently what therapeutic goal, is optimal for brain perfusion. Moreover, there is limited data on how BP affects hippocampal perfusion, a structure critically involved in memory. We conducted a cross-sectional (n=445) and longitudinal (n=185) study of adults and elderly without dementia or clinically apparent stroke, who underwent clinical examination and brain perfusion assessment (age 69.2±7.5 years, 62% women, 45% hypertensive). Linear models were used to test baseline BP-blood flow relationship and to examine how changes in BP influence changes in perfusion. In the entire group, systolic BP (SBP) was negatively related to cortical (β=−0.13,
P
=0.005) and hippocampal blood flow (β=-0.12,
P
=0.01). Notably, this negative relationship was apparent already in subjects without hypertension. Hypertensive subjects showed a quadratic relationship between SBP and hippocampal blood flow (β=−1.55,
P
=0.03): Perfusion was the highest in subjects with mid-range SBP around 125 mm Hg. Longitudinally, in hypertensive subjects perfusion increased with increased SBP at low baseline SBP but increased with decreased SBP at high baseline SBP. Cortical and hippocampal perfusion decrease with increasing SBP across the entire BP spectrum. However, in hypertension, there seems to be a window of mid-range SBP which maximizes perfusion.
Norepinephrine-Induced Stimulation of Kir4.1/Kir5.1 Is Required for the Activation of NaCl Transporter in Distal Convoluted Tubule
Authors: Duan Xin-Peng , Gu Li , Xiao Yu , Gao Zhong-Xiuzi , Wu Peng , Zhang Yun-Hong , Meng Xin-Xin , Wang Jun-Lin , Zhang Dan-Dan , Lin Dao-Hong , Wang Wen-Hui , Gu Ruimin
Published: December 2018

The stimulation of β–adrenergic receptor increases thiazide-sensitive NaCl cotransporter (NCC), an effect contributing to salt-sensitive hypertension by sympathetic stimulation. We now test whether the stimulation of β–adrenergic receptor-induced activation of NCC is achieved through activating basolateral Kir4.1 in the distal convoluted tubule (DCT). Application of norepinephrine increased the basolateral 40 pS K
+
channel (Kir4.1/Kir5.1 heterotetramer) in the DCT. The stimulatory effect of norepinephrine on the K
+
channel was mimicked by cAMP analogue but abolished by inhibiting PKA (protein kinase A). Also, the effect of norepinephrine on the K
+
channel in the DCT was recapitulated by isoproterenol but not by α–adrenergic agonist and blocked by propranolol, suggesting that norepinephrine effect on the K
+
channel was mediated by β–adrenergic receptor. The whole-cell recording shows that norepinephrine and isoproterenol increased DCT K
+
currents and shifted the K
+
current (
I
K
) reversal potential to negative range (hyperpolarization). Continuous norepinephrine perfusion (7 days) increased DCT K
+
currents, hyperpolarized
I
K
reversal potential, and increased the expression of total NCC/phosphorylated NCC, but it had no significant effect on the expression of NKCC2 (type 2 Na-Cl-K cotransporter) and ENaC-α (epithelial Na channel-α subunit). Renal clearance study demonstrated that norepinephrine perfusion augmented thiazide-induced urinary Na
+
excretion only in wild-type but not in kidney-specific Kir4.1 knockout mice, suggesting that Kir4.1 is required for mediating the effect of norepinephrine on NCC. However, norepinephrine perfusion did not affect urinary K
+
excretion. We conclude that the stimulation of β–adrenergic receptor activates the basolateral Kir4.1 in the DCT and that the activation of Kir4.1 is required for norepinephrine-induced stimulation of NCC.
Novel Treatment of Hypertension by Specifically Targeting E2F for Restoration of Endothelial Dihydrofolate Reductase and eNOS Function Under Oxidative Stress
Authors: Li Hong , Li Qiang , Zhang Yixuan , Liu Wenting , Gu Bo , Narumi Taro , Siu Kin Lung , Youn Ji Youn , Liu Peiqing , Yang Xia , Cai Hua
Published: December 2018

We have shown that hydrogen peroxide (H
2
O
2
) downregulates tetrahydrobiopterin salvage enzyme DHFR (dihydrofolate reductase) to result in eNOS (endothelial NO synthase) uncoupling and elevated blood pressure. Here, we aimed to delineate molecular mechanisms underlying H
2
O
2
downregulation of endothelial DHFR by examining transcriptional pathways hypothesized to modulate DHFR expression and effects on blood pressure regulation of targeting these novel mechanisms. H
2
O
2
dose and time dependently attenuated DHFR mRNA and protein expression and enzymatic activity in endothelial cells. Deletion of E2F-binding sites, but not those of Sp1 (specificity protein 1), abolished H
2
O
2
attenuation of DHFR promoter activity. Overexpression of E2F1/2/3a activated DHFR promoter at baseline and alleviated the inhibitory effect of H
2
O
2
on DHFR promoter activity. H
2
O
2
treatment diminished mRNA and protein expression of E2F1/2/3a, whereas overexpression of E2F isoforms increased DHFR protein levels. Chromatin immunoprecipitation assay indicated direct binding of E2F1/2/3a to the DHFR promoter, which was weakened by H
2
O
2
. E2F1 RNA interference attenuated DHFR protein levels, whereas its overexpression elevated tetrahydrobiopterin levels and tetrahydrobiopterin/dihydrobiopterin ratios in vitro and in vivo. In Ang II (angiotensin II)–infused mice, adenovirus-mediated overexpression of E2F1 markedly abrogated blood pressure to control levels, by restoring endothelial DHFR function to improve NO bioavailability and vasorelaxation. Bioinformatic analyses confirmed a positive correlation between E2F1 and DHFR in human endothelial cells and arteries, and downregulation of both by oxidized phospholipids. In summary, endothelial DHFR is downregulated by H
2
O
2
transcriptionally via an E2F-dependent mechanism, and that specifically targeting E2F1/2/3a to restore DHFR and eNOS function may serve as a novel therapeutic option for the treatment of hypertension.
HFE
H63D Polymorphism and the Risk for Systemic Hypertension, Myocardial Remodeling, and Adverse Cardiovascular Events in the ARIC Study
Authors: Selvaraj Senthil , Seidelmann Sara , Silvestre Odilson M. , Claggett Brian , Ndumele Chiadi E. , Cheng Susan , Yu Bing , Fernandes-Silva Miguel M. , Grove Megan L. , Boerwinkle Eric , Shah Amil M. , Solomon Scott D.
Published: December 2018

H63D has been identified as a novel locus associated with the development of hypertension. The quantitative risks for hypertension, cardiac remodeling, and adverse events are not well studied. We analyzed white participants from the ARIC study (Atherosclerosis Risk in Communities) with H63D genotyping (N=10 902). We related genotype status to prevalence of hypertension at each of 5 study visits and risk for adverse cardiovascular events. Among visit 5 participants (N=4507), we related genotype status to echocardiographic features. Frequencies of wild type (WT)/WT, H63D/WT, and H63D/H63D were 73%, 24.6%, and 2.4%. The average age at baseline was 54.9±5.7 years and 47% were men. Participants carrying the H63D variant had higher systolic blood pressure (
P
=0.004), diastolic blood pressure (0.012), and more frequently had hypertension (
P
<0.001). Compared with WT/WT, H63D/WT and H63D/H63D participants had a 2% to 4% and 4% to 7% absolute increase in hypertension risk at each visit, respectively. The population attributable risk of H63D for hypertension among individuals aged 45 to 64 was 3.2% (95% CI, 1.3–5.1%) and 1.3% (95% CI, 0.0–2.4%) among individuals >65 years. After 25 years of follow-up, there was no relationship between genotype status and any outcome (
P
>0.05). H63D/WT and H63D/H63D genotypes were associated with small differences in cardiac remodeling. In conclusion, the
HFE
H63D variant confers an increased risk for hypertension per allele and, given its frequency, accounts for a significant number of cases of hypertension. However, there was no increased risk for adverse cardiovascular events or substantial left ventricular remodeling.
Hypertension Is Predicted by Both Large and Small Artery Disease
Authors: Kario Kazuomi , Kanegae Hiroshi , Oikawa Takamitsu , Suzuki Kenji
Published: December 2018

Both small and large artery disease might precede the development of hypertension. However, no prospective trial has yet determined the role of small and large artery disease on the rate of new-onset hypertension in a normotensive general population. This study investigated associations between both arterial stiffness and small artery retinopathy and the development of hypertension in adults from Japan. Normotensive individuals who underwent a baseline health checkup from 2005 to 2015 and at least 1 annual follow-up were eligible. The cardio-ankle vascular index (CAVI) was measured, and retinal fundus photography was performed at baseline. Follow-up visits included measurement of clinic blood pressure. The primary end point was new-onset hypertension (blood pressure ≥140/90 mm Hg or initiation of antihypertensive medication with self-reported hypertension). The analysis included 34 649 subjects (mean age, 44.2 years; 46.4% male). Mean follow-up duration was 3.18±2.50 years. The cumulative incidence of new-onset hypertension during the 10-year follow-up period was 40% of patients overall, with rates increasing in parallel with baseline CAVI (quartile [Q]1, 23%; Q2, 33%; Q3, 42%; Q4, 58%;
P
<0.001), and as the severity of retinopathy increased (
P
<0.001). CAVI showed good discriminative ability for detecting new-onset hypertension. In multivariate analysis, both CAVI and small artery retinopathy were independent predictors of hypertension development. There was no interaction between CAVI and small artery retinopathy with respect to incident hypertension. In conclusion, we showed that both large and small artery disease predict future hypertension independently of each other and confounding risk factors in a general normotensive population.
Obesity, High Blood Pressure, and Physical Activity Determine Vascular Phenotype in Young Children
Authors: Köchli Sabrina , Endes Katharina , Steiner Ramona , Engler Luca , Infanger Denis , Schmidt-Trucksäss Arno , Zahner Lukas , Hanssen Henner
Published: December 2018

Cardiovascular disease often develops during childhood, but the determinants of vascular health and disease in young children remain unclear. The study aimed to investigate the association of obesity and hypertension, as well as physical fitness with retinal microvascular health and large artery stiffness, in children. In this cross-sectional study, 1171 primary school children (aged 7.2±0.4 years) were screened for central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE) diameters, pulse wave velocity (PWV), body mass index, blood pressure (BP), and cardiorespiratory fitness by standardized procedures for children. BP was categorized according to the reference values of the population-based German KiGGS study (Kinder- und Jugendgesundheitssurvey [Children- and Adolescents Health Survey]) and the American Academy of Pediatrics guidelines. Overweight (mean [95% CI]: CRAE, 200.5 [197.9–203.2] µm; CRVE, 231.4 [228.6–234.2] µm; PWV, 4.46 [4.41–4.52] m/s) and obese children (CRAE, 200.5 [196.4–204.7] µm; CRVE, 233.3 [229.0–237.7] µm; PWV, 4.51 [4.43–4.60] m/s) had narrower CRAE, wider CRVE, and higher PWV compared with normal-weight children (CRAE: 203.3 [202.5–204.1] µm,
P
<0.001; CRVE: 230.1 [229.1–230.9] µm,
P
=0.07; PWV: 4.33 [4.31–4.35] m/s,
P
<0.001). Children with high-normal BP (CRAE, 202.5 [200.0–205.0] µm; PWV, 4.44 [4.39–4.49] m/s) and BP in the hypertensive range (CRAE, 198.8 [196.7–201.0] µm; PWV, 4.56 [4.51–4.60] m/s) showed narrower CRAE, as well as higher PWV, compared with normotensive peers (CRAE: 203.7 [202.9–204.6] µm,
P
<0.001; PWV: 4.30 [4.28–4.32] m/s,
P
<0.001). With each unit increase of body mass index and systolic BP, CRAE decreased and PWV increased significantly. Children with the highest cardiorespiratory fitness had wider CRAE, narrower CRVE, and lower PWV compared with least fit children. Childhood obesity and hypertension, even at preclinical stages, are associated with microvascular and macrovascular impairments in young children. Primary prevention programs targeting physical activity behavior may have the potential to counteract development of small and large vessel disease early in life.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT02853747.
Melanocortin-4 Receptor Deficiency Attenuates Placental Ischemia-Induced Hypertension in Pregnant Rats
Authors: Spradley Frank T. , Palei Ana C. , Anderson Christopher D. , Granger Joey P.
Published: December 2018

Preeclampsia is a pregnancy-specific disorder of new-onset hypertension linked to placental ischemia. While obesity is a major risk factor for preeclampsia, not all obese pregnant women develop pregnancy-induced hypertension or preeclampsia. Previously, we reported that placental ischemia-induced hypertension is dependent upon intact signaling of the sympathetic nervous system. Moreover, in various models of obesity, blockade of MC4R (melanocortin-4 receptor) signaling protects against the development of hypertension via suppression of the sympathetic nervous system. Less is known about this pathway during obese pregnancy. Although blockade of MC4R may lead to increased body weight during pregnancy, we tested the hypothesis that placental ischemia-induced hypertension is attenuated in obese MC4R-deficient pregnant rats. On gestational day 14, MC4R wild-type or heterozygous-deficient (MC4R-def) rats were subjected to chronic placental ischemia via the reduced uterine perfusion pressure procedure or Sham surgery then examined on gestational day 19. In Sham MC4R-def versus Sham wild-type pregnant rats, there was increased body weight, fat mass, and circulating leptin levels but they had similar fetus weights. Reduced uterine perfusion pressure reduced fetus weights in both strains. Reduced uterine perfusion pressure increased blood pressure in wild-type rats but this response was significantly attenuated in MC4R-def rats, although blood pressure was elevated in Sham MC4R-def over Sham wild-type. These data indicate that while obese MC4R-def pregnant rats have higher blood pressure during pregnancy, placental ischemia-induced hypertension is attenuated in obese MC4R-def pregnant rats. Thus, obese women with abnormal MC4R signaling may be less susceptible to the development of placental ischemia-induced hypertension.
Acute Increases in Serum Creatinine After Starting Angiotensin-Converting Enzyme Inhibitor-Based Therapy and Effects of its Continuation on Major Clinical Outcomes in Type 2 Diabetes Mellitus
Authors: Ohkuma Toshiaki , Jun Min , Rodgers Anthony , Cooper Mark E. , Glasziou Paul , Hamet Pavel , Harrap Stephen , Mancia Giuseppe , Marre Michel , Neal Bruce , Perkovic Vlado , Poulter Neil , Williams Bryan , Zoungas Sophia , Chalmers John , Woodward Mark ,   on behalf of the ADVANCE Collaborative Group
Published: December 2018

Discontinuation of angiotensin-converting enzyme (ACE) inhibitor is recommended if patients experience ≥30% acute increase in serum creatinine after starting this therapy. However, the long-term effects of its continuation or discontinuation on major clinical outcomes after increases in serum creatinine are unclear. In the ADVANCE trial (Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation), 11 140 diabetes mellitus patients were randomly assigned to perindopril-indapamide or placebo after a 6-week active run-in period. The current study included 11 066 participants with 2 serum creatinine measurements recorded before and during the active run-in period (3 weeks apart). Acute increase in creatinine was determined using these 2 measurements and classified into 4 groups: increases in serum creatinine of <10%, 10% to 19%, 20% to 29%, and ≥30%. The primary study outcome was the composite of major macrovascular events, new or worsening nephropathy, and all-cause mortality. An acute increase in serum creatinine was associated with an elevated risk of the primary outcome (
P
for trend <0.001). The hazard ratios were 1.11 (95% CI, 0.97–1.28) for those with an increase of 10% to 19%, 1.34 (1.07–1.66) for 20% to 29%, and 1.44 (1.15–1.81) for ≥30%, compared with <10%. However, there was no evidence of heterogeneity in the benefit of randomized treatment effects on the outcome across subgroups defined by acute serum creatinine increase (
P
for heterogeneity=0.94). Acute increases in serum creatinine after starting perindopril-indapamide were associated with greater risks of subsequent major clinical outcomes. However, the continuation of angiotensin-converting enzyme inhibitor-based therapy reduced the long-term risk of major clinical outcomes, irrespective of acute increase in creatinine.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00145925.
How Many Doses Make a Difference? An Analysis of Secondary Prevention of Rheumatic Fever and Rheumatic Heart Disease
Authors: de Dassel Jessica Langloh , de Klerk Nick , Carapetis Jonathan Rhys , Ralph Anna P.
Published: December 2018

Background

Acute rheumatic fever (
ARF
) and rheumatic heart disease cause substantial burdens worldwide. Long‐term antibiotic secondary prophylaxis is used to prevent disease progression, but evidence for benefits of different adherence levels is limited. Using data from northern Australia, we identified factors associated with adherence, and the association between adherence and
ARF
recurrence, progression to rheumatic heart disease, worsening or improvement of rheumatic heart disease, and mortality.

Methods and Results

Factors associated with adherence (percent of doses administered) were analyzed using logistic regression. Nested case–control and case–crossover designs were used to investigate associations with clinical outcomes; conditional logistic regression was used to estimate odds ratios (
OR
) with 95% CIs Adherence estimates (7728) were analyzed. Being female, younger, having more‐severe disease, and living remotely were associated with higher adherence. Alcohol misuse was associated with lower adherence. The risk of
ARF
recurrence did not decrease until ≈40% of doses had been administered. Receiving <80% was associated with a 4‐fold increase in the odds of
ARF
recurrence (case–control
OR
: 4.00 [95%
CI
: 1.7–9.29], case–crossover
OR
: 3.31 [95%
CI
: 1.09–10.07]) and appeared to be associated with increased all‐cause mortality (case–control
OR
: 1.90 [95%
CI
: 0.89–4.06]; case–crossover
OR
1.91 [95%
CI
: 0.51–7.12]).

Conclusions

We show for the first time that increased adherence to penicillin prophylaxis is associated with reduced
ARF
recurrence, and a likely reduction in mortality, in our setting. These findings can motivate patients to receive doses since even relatively low adherence can be beneficial, and additional doses further reduce adverse clinical outcomes.
Palaearctic oak gallwasps galling oaks (Quercus) in the section Cerris: re-appraisal of generic limits, with descriptions of new genera and species (Hymenoptera: Cynipidae: Cynipini)
Authors: MELIKA GEORGE , PUJADE-VILLAR JULI , ABE YOSHIHISA , TANG CHANG-TI , NICHOLLS JAMES , WACHI NAKATADA , IDE TATSUYA , YANG MAN-MIAO , PÉNZES ZSOLT , CSÓKA GYÖRGY , STONE GRAHAM N.
Published: December 2018

We discuss the taxonomy of oak gallwasps (Hymenoptera: Cynipidae: Cynipini) whose lifecycle involves only Palaearctic oaks (Quercus subgen. Quercus) in the section Cerris. Recent phylogenetic reconstructions support a deep split between such Cerris-associated species in the genera Aphelonyx, Dryocosmus, Plagiotrochus, Neuroterus, Pseudoneuroterus and species and genera associated with oaks in the section Quercus sensu stricto. We reappraise the generic limits of the Cerris-associated genera, proposing new limits for Dryocosmus, Pseudoneuroterus and Neuroterus, establishing a new genus Cerroneuroterus, elevating Latuspina to a genus level, reestablishing the genera Chilaspis and Trichagalma and proposed new species name combinations. We provide a new key to oak gallwasp genera of the Palaearctic and keys to all species of genera associated with Cerris section oaks. We describe five new species, Aphelonyx kordestanica, Trichagalma formosana, Dryocosmus jungalii, Pseudoneuroterus mazandarani, and P. nichollsi.
Synopsis of Australian agathidine wasps (Hymenoptera: Braconidae: Agathidinae)
Authors: STEVENS NICHOLAS B. , AUSTIN ANDREW D. , JENNINGS JOHN T.
Published: December 2018

Agathidinae is a large subfamily of braconid wasps that are koinobiont endoparasitoids of lepidopteran larvae. Although the group is relatively well studied in the northern hemisphere, the Australian fauna is poorly known, with only 36 species recorded from the continent. This study presents a synopsis of the genera and species that occur in Australia, including a key to genera, information on their distribution and apparent species richness, and a list of species according to the latest generic concepts. Ten genera occur in Australia: Amputostypos Sharkey, Baeognatha Kokujev, Biroia Szépligeti, Braunsia Kriechbaumer, Coccygidium Saussure, Cremnops Foerster, Disophrys Foerster, Euagathis Szépligeti, Lytopylus Foerster and Therophilus Wesmael, with Lytopylus known only from a single introduced species. Baeognatha stat. rev. is taken out of synonymy with Therophilus and two genera are synonymised: Platyagathis Turner with Disophrys (syn. nov.) and Camptothlipsis with Baeognatha (syn. nov.). The genera Agathis Latreille and Bassus Fabricius are excluded from the Australian fauna, as the species described under these genera are here transferred to Therophilus, and no other species of either genus have been discovered from the continent. Further, the genera Baeognatha and Coccygidium are recorded from Australia for the first time, although not represented by any described species. The following new combinations are proposed: Amputostypos dilutum (Turner), comb. nov. (from Hypsostypos), A. exornatum (Turner), comb. nov. (from Hypsostypos), Disophrys leaena (Turner), comb. nov. (from Platyagathis), Lytopylus rufipes (Nees von Esenbeck) comb. nov. (from Bassus), Therophilus antipodus (Ashmead) comb. nov. (from Orgiloneura), T. festinatus (Turner), comb. nov. (from Bassus), T. latibalteatus (Cameron) comb. nov. (from Agathis), T. leucogaster (Holmgren) comb. nov. (from Agathis), T. malignus (Turner). comb. nov. (from Bassus), T. martialis (Turner) comb. nov. (from Agathis), T. meridionalis (Turner comb. nov. (from Bassus), T. minimus (Turner) comb. nov. (from Bassus), T. minor (Szépligeti) comb. nov. (from Bassus), T. pedunculatus (Szépligeti) comb. nov. (from Bassus), T. ruficeps (Szépligeti). comb. nov. (from Bassus), T. rufithorax (Turner) comb. nov. (from Agathis), T. rufobrunneus (Turner) comb. nov. (from Agathis), T. rugosus (Turner) comb. nov. (from Bassus), T. tricolor (Szépligeti) comb nov. (from Bassus), and T. xanthopsis (Turner) comb. nov. (from Agathis). In addition, Bassus tenuissimus (Turner) is synonomised with T. ruficeps (Szépligeti) syn. nov., and Agathis dimidiata (Brullé) is designated a nomen dubium.
Redescription of the species Procloeon (Pseudocentroptilum) fascicaudale (Sowa, 1985) (Ephemeroptera: Baetidae) with notes to its taxonomic position, biology and distribution
Authors: SROKA PAVEL , GODUNKO ROMAN J. , SOLDÁN TOMÁŠ
Published: December 2018

Based on the extensive material recently collected on the Island of Rhodos, Greece (terra typica) in May, 2005, a redescription of Procloeon (Pseudocentroptilum) fascicaudale (Sowa, 1985) is presented. Larval characters are completed, female subimago described and the egg chorionic structures illustrated by means of scanning electron microscopy for the first time. Variability in color patterns and critical characters distinguishing eggs, larvae and male imagines from other Westpalaearctic species of the subgenus Pseudocentroptilum Bogoescu, 1947 (the representatives of the Procloeon (Pseudocentroptilum) motasi species-group in particular) are described and discussed. Distributional patterns of the species, its abundance, possible faunistic origin, some aspects of larval and imago’s biology, and life cycle of the species are briefly stated. Delimitation and recent concepts of the taxa Procloeon Bengtsson, 1915 and Pseudocentroptilum within the subfamily Cloeoninae Kazlauskas, 1972, taxonomic position and affinities of P. fascicaudale are discussed.
A new Neotropical species of the genus Stenochironomus Kieffer (Diptera: Chironomidae) with wood-mining larvae
Authors: DANTAS GALILEU P. S. , HAMADA NEUSA , MENDES HUMBERTO F.
Published: December 2018

A new Neotropical species of the genus Stenochironomus Kieffer, 1919 is described and illustrated based on adult male, pupa and larva. The larvae were reared from decayed wood collected in black-water Amazonian streams.
Trypanorhynch cestodes of elasmobranchs from the Persian Gulf
Authors: HASELI MOHAMMAD , MALEK MASOUMEH , PALM HARRY WILHELM
Published: December 2018

The first large scale study of trypanorhynch cestodes of elasmobranchs from the Persian Gulf was carried out during November to December 2007. A total of 194 elasmobranch specimens belonging to six families and 15 species was infested with the following cestodes, most representing new locality and 23 new host records: Kotorella pronosoma (Stossich, 1901), Kotorella sp. and Nybelinia spp. from the stomach, and Pterobothrium lesteri Campbell & Beveridge, 1996, Pseudogrillotia perelica (Shuler, 1938), Callitetrarhynchus gracilis Pintner, 1931, Proemotobothrium southwelli Beveridge & Campbell, 2001, Otobothrium carcharidis (Shipley & Hornell, 1906), Otobothrium sp., Halysiorhynchus macrocephalus (Shipley & Hornell, 1906), Trygonicola macropora (Shipley & Hornell, 1906), Eutetrarhynchus platycephali Palm, 2004, Eutetrarhynchus sp., Oncomegoides celatus Beveridge & Campbell, 2005, Parachristianella monomegacantha Kruse, 1959, P. indonesiensis Palm, 2004, Parachristianella sp., Pseudochristianella southwelli Campbell & Beveridge, 1990, Prochristianella macracantha Palm, 2004, Prochristianella spp. and Dollfusiella spp. from the host intestine. The most abundant trypanorhynchs were Dollfusiella that were found inseven different elasmobranch species. Pastinachus cf. sephen (Forsskål) was most species rich, with at least eight different trypanorhynch species. Highest prevalence (100%) was recorded for Pseudochristianella southwelli with a maximum intensity of 24 in Rhinobatos cf. punctifer Compagno & Randall (n=5). Within the elasmobranchs, highest prevalence (83.3%) was seen for Otobothrium carcharidis with a maximum intensity of 39 in Rhizoprionodon acutus (Rüppell). Host specificity values were recalculated for Kotorella pronosoma, Pseudogrillotia perelica, Callitetrarhynchus gracilis and Proemotobothrium southwelli.
Revised taxonomy and redescription of two species of the Peripatidae (Onychophora) from Brazil: a step towards consistent terminology of morphological characters
Authors: DE SENA OLIVEIRA IVO , WIELOCH ALFREDO HANNEMANN , MAYER GEORG
Published: December 2018

Based on the supposed quadrangular shape of the basal pieces of dorsal primary papillae, several species of the “Caribbean group” of the neotropical Peripatidae, including Macroperipatus acacioi and M. machadoi, were assigned to Macroperipatus. So far, the quadrangular shape of dermal papillae was confirmed only for M. torquatus, the type species of the genus. Previous observations revealed that the putatively quadrangular shape reported from other species of the “Caribbean group” might be a fixation artefact. Hence, detailed reinvestigations of all putative Macroperipatus species are required to clarify their taxonomy. In the present study, two species of the “Caribbean group”, M. acacioi and M. machadoi, are analyzed and redescribed, based on type material and topotype specimens collected at the corresponding type localities. The original descriptions of both species are complemented with data obtained from scanning electron microscopy, in addition to conventional morphological methods. The quadrangular bases of primary papillae are shown to be absent from M. acacioi and M. machadoi, thus suggesting that these two species are not closely related to M. torquatus. The new data instead suggest that these two species are representatives of Epiperipatus: E. acacioi comb. nov. and E. machadoi comb. nov.. The present study highlights the use of scanning electron microscopy for clarifying the taxonomy and phylogeny of the neotropical Peripatidae. It also reveals gaps in taxon sampling and problems regarding the ambiguous terminology of morphological characters used for describing the anatomy of peripatids. An attempt is made towards a consistent terminology for species (re)descriptions and studies of onychophoran anatomy and phylogeny.
Syllinae (Polychaeta: Syllidae) from Australia. Part 3. Genera Alcyonosyllis, Genus A, Parahaplosyllis, and Trypanosyllis (Trypanobia)
Authors: SAN MARTÍN GUILLERMO , HUTCHINGS PAT , AGUADO MARÍA TERESA
Published: December 2018

Large collections of Australian Syllidae (Polychaeta) from the Australian Museum (Sydney) have been examined and identified, together with material from the Hamburgische Zoologische Museum der Universität (Hamburg, Germany), as well as some specimens from other museums. All known Australian species of the subfamily Syllinae belonging to the genera Alcyonosyllis Glasby & Watson, 2001 (1 species), Genus A (1 species), Parahaplosyllis Hartmann-Schröder, 1990 (1 species), and Trypanosyllis (Trypanobia) Imajima & Hartman, 1964 (2 species), are fully described and figured, except Alcyonosyllis phili Glasby & Watson, 2001 that recently was described based on Australian material.
Review of Empoasca (Distantasca) Dworakowska (Hemiptera: Cicadellidae: Typhlocybinae: Empoascini), with description of two new species from China
Authors: ZHANG YA-LIN , LIU YANG , QIN DAO-ZHENG
Published: December 2018

A key to known species of the subgenus Empoasca (Distantasca) is provided. Two new species, E. (Distantasca) latibasis Zhang and Liu sp. n. and E. (D.) tuberculata Zhang and Liu sp. n., are described and illustrated from Yunnan Province (SW China).
A new dwarf sentinel crab from Mayotte Island, western Indian Ocean (Decapoda: Brachyura: Macrophthalmidae)
Authors: POUPIN JOSEPH , BOUCHARD JEAN-MARIE
Published: December 2018

A new sentinel crab of the genus Macrophthalmus is described from Mayotte Island, western Indian Ocean. The new species is remarkable by its very small size, with a carapace width not longer than 5.5 mm for the largest ovigerous females. It is closely related to Macrophthalmus (Chaenostoma) boscii Audouin, 1826.Affinities of these two species are discussed.
Elattoneura mauros sp. nov. (Odonata: Zygoptera: Protoneuridae) from Sarawak, Malaysian Borneo
Authors: DOW RORY A. , CHOONG CHEE YEN , NG YONG FOO
Published: December 2018

Five species of Elattoneura Cowley, 1935 have been recorded from Sundaland: E. analis (Selys, 1860), E. aurantiaca (Selys, 1886), E. coomansi Lieftinck, 1937, E. erythromma Lieftinck, 1953 and E. longispina Lieftinck, 1937 (Lieftinck 1954). All of these species occur on the island of Borneo (Orr 2003), but only E. erythromma appears to be endemic to Borneo.
Phylogenetic relationships in the genus Astropecten Gray (Paxillosida: Astropectinidae) on a global scale: molecular evidence for morphological convergence, species-complexes and possible cryptic speciation
Authors: ZULLIGER DEBORAH E. , LESSIOS H. A.
Published: December 2018

With over 150 described species, Astropecten Gray (Paxillosida:Astropectinidae) is one of the most species-rich genera among sea stars. This diversity is remarkable, because most species of Astropecten have a long-lived planktotrophic larval stage, which would be expected to lead to a low speciation rate. The taxonomy of this genus is complex and not well resolved, and phylogenetic relationships have only been addressed in the beginning of the last century. In order to resolve general taxonomic issues, identify speciation patterns and estimate species diversity within the genus Astropecten, we inferred a molecular phylogeny of 117 specimens of Astropecten belonging to 40 species from around the world using mitochondrial DNA (mtDNA) sequences of 12S rRNA, 16S rRNA and cytochrome oxidase subunit I (COI). We compared the resulting molecular phylogeny to a previously published morphological one by Döderlein and investigated the possibility of morphological convergence in species from different geographic regions. Finally, we also aimed at identifying potentially problematic descriptions and/or signs of cryptic speciation in Astropecten. The global molecular phylogeny exhibited three main clades, each containing specimens of the same geographic region: 1. the IndoPacific; 2. the Neotropics; and 3. the eastern Atlantic and Mediterranean. Phylogenetic inferences based on mtDNA indicate that morphological and ecological convergence has taken place in Astropecten, resulting in allopatric non-sister taxa with similar morphologies and habitat preferences. The comparison to Döderlein’s morphological phylogeny reveals congruence on the whole but many discrepancies on a local scale, indicating that meaningful morphological characters are not easily identified and categorized in Astropecten. Our results also reveal that A. polyacanthus Müller & Tröschel and A. indicus Döderlein are species-complexes; cryptic speciation may have occurred within each of these morphospecies. Furthermore, several variants, previously presumed to be conspecific, exhibit genetic distances large enough to justify recognizing them as separate species.
Re-assessment of the Reinwardt’s Gliding Frog, Rhacophorus reinwardtii (Schlegel 1840) (Anura: Rhacophoridae) in Southern Thailand and Peninsular Malaysia and its re-description as a new species
Authors: ONN CHAN KIN , GRISMER L. LEE
Published: December 2018

Rhacophorus reinwardtii from Southern Thailand and Peninsular Malaysia is found to be morphologically distinct from Javan and Bornean populations and is herein described as a new species. Rhacophorus norhayatii sp nov. can be differentiated from R. reinwardtii by having a larger maximum SVL in males (64.7 mm vs. 55 mm); lacking spots on dorsum; higher degree of interdigital web pigmentation on hands and feet; and rusty brown markings on the flanks. This study adds to the growing list of taxonomic changes in Sunda Shelf taxa by demonstrating that species previously thought to be widely distributed across Sundaland are indeed distinct lineages worthy of species recognition.
Taxonomy of the genus Craspedomerus Bernhauer, 1911 (Coleoptera: Staphylinidae: Philonthina) from China
Authors: LI LIANG , ZHOU HONG-ZHANG
Published: December 2018

Three new species of the genus Craspedomerus from China are described and illustrated: C. giganteus Li & Zhou sp. n. from Sichuan, C. gongshanus Li & Zhou sp. n. from Yunnan and C. zhangi Li & Zhou sp. n. from Tibet. Four species are reported for the first time from China: C. sinetuber (Coiffait, 1977a) from Tibet, C. cyanipennis Scheerpeltz, 1976b, C. ganeshensis Coiffait, 1983 and C. glenoides (Schubert, 1908) from Yunnan. These four and two additional species previously recorded from China (C. beckeri Bernhauer, 1934 and C. violaceipennis Cameron, 1928 are redescribed and illustrated. Sensory peg setae located on the underside of the paramere of the aedeagus of all nine Chinese species are compared using scanning electron microscopy (SEM) and the result shows that this character is useful for species identification. A key to the Chinese species of Craspedomerus is presented and geographical distribution of all sixteen species of Craspedomerus is mapped.
Description of the final instar of Macrothemis heteronycha (Calvert) (Anisoptera: Libellulidae)
Authors: COSTA JANIRA M. , CARRIÇO CÉSAR , SANTOS TATIANA C. , MASCARENHAS BERNARDO. J. A.
Published: December 2018

The Neotropical genus Macrothemis comprises 40 species described to date (von Ellenrieder, 2007) of which 22 occur in Brazil. The immature stages of this stream-dwelling genus are poorly known (Costa et al., 2004), as larvae of only nine species have been described: M. aurimaculata Donnelly, 1984 (Ramírez & Novelo-Gutiérrez,1999), M. celeno Selys in Sagra, 1857 (Klots, 1932), M. hahneli Ris, 1913 (von Ellenrieder, 2007), M. inacuta Calvert, 1898 (Novelo-Gutiérrez & Ramírez, 1998), M. inequiunguis Calvert, 1895 (Ramírez and Novelo-Gutiérrez,1999), M. meurgeyi Daigle, 2007 (Meurgey, 2009), M. musiva Calvert, 1898 (Santos, 1970), M. pseudimitans Calvert, 1898 (Limongi, 1989) and M. ultima González-Soriano, 1992 (Novelo-Gutiérrez, 2006).
A new data of freshwater amphipod of genus Niphargus Schiödte, 1849 from Lorestan Province in Iran
Authors: ESMAEILI-RINEH SOMAYEH
Published: December 2018

Niphargus lorestanensis sp.nov., a new species from west of Iran, is described and illustrated based on the analysis of morphological characters. Previous studies supported new species status using the phylogenetic analyses based on CO1, 28srDNA and H3 data in Esmaeili-Rineh et al., 2015. This species can be distinguished from other Iranian species by the equal length of palpus to outer lobe in maxilla I, the presence of multiple supporting robust setae in palmar corner of gnathopods I–II, not reaching dactyli to posterior margin of propodi in gnathopods I to II and trapezoid shape of propodi in gnathopods I–II. The Iranian fauna of Niphargus is currently represented by 18 described species.