bluuebunny/crossref_metadata_2025 huggingface dataset:
Ethylacrylat [MAK Value Documentation in German language, 2016]
Authors: Kreis P. , Michaelsen S. , Bartsch R. , van Thriel C. , Lessmann H. , Schnuch A. , Göen T. , Bader M. , Hartwig A. ,   MAK Commission
Published: January 2016

MAK Value Documentation for Ethyl acrylate

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated the maximum concentration at the workplace (MAK value) of ethyl acrylate of 5 ml/m
3
, considering all toxicity endpoints. Available unpublished study reports and publications are described in detail. The critical effect of ethyl acrylate is irritation of eye and nose in humans and the olfactory mucosa in rats and mice. The chronic NOAEC in rats is 5 ml/m
3
. Since 2014 the Commission uses an empirical approach to set MAK values for substances with critical effects on the upper respiratory tract or the eyes. Accordingly, the MAK value has to be lowered to 2 ml/m
3
, which is confirmed in a recent volunteer study with a NOAEC of 2.5 and a LOAEC of 5 ml ethyl acrylate/m
3
. As local effects are critical, the assignment to Peak Limitation Category I and the excursion factor of 2 are confirmed. Developmental toxicity studies with ethyl acrylate show that damage to the embryo or foetus is unlikely if the MAK value is observed, and the assignment to Pregnancy Risk Group C is retained. Ethyl acrylate is not genotoxic in vivo and not carcinogenic. Skin contact may contribute significantly to systemic toxicity and ethyl acrylate is designated with an “H” notation. The available data confirm that the substance is a skin sensitizer and the designation with “Sh” is retained. There are no data concerning the potential for respiratory sensitization.
2‐Aminoethanol [MAK Value Documentation in German language, 2016]
Authors: Laube B. , Bartsch R. , Hartwig A. ,   MAK Commission
Published: January 2016

MAK Value Documentation for 2‐Aminoethanol

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated the maximum concentration at the work place (MAK value) of 2‐aminoethanol, considering the endpoints respiratory tract irritation, developmental toxicity, and skin absorption. Available unpublished study reports are described in detail.

Critical effect of 2‐aminoethanol is the local respiratory tract irritation. New 5‐day and 28‐day‐guideline‐studies with rats show time‐ and dose‐dependent effects in larynx (squamous metaplasia, inflammation, necrosis), trachea (squamous metaplasia, inflammation), and lung (hyperplasia of mucous and goblet cells). The NOAEC is 10 mg/m
3
(3,95 ml/m
3
). Since 2014, the Commission uses an empirical approach to set MAK values for substances with critical effects on the upper respiratory tract or the eyes. Based on this approach, a concentration of 0.22 ml/m
3
for the work place air can be calculated from this study, resulting in a MAK value of 0.2 ml/m
3
. Since the critical effect is irritation, Peak Limitation Category I is retained with an excursion factor of 1 as the substance is corrosive.

After scaling the oral NOAEL for developmental toxicity of 75, 225, and 500 mg/kg body weight and day for rabbits (dermal) and rats (dermal, oral), respectively, to an inhalation concentration at the work place, the differences to the MAK value, are considered sufficient, and damage to the embryo or foetus is unlikely when the MAK value is observed. Therefore, classification in Pregnancy Risk Group C is confirmed.

Absorption via skin does not contribute significantly to the systemic toxicity of 2‐aminoethanol.
4‐Methyl‐3‐penten‐2‐on [MAK Value Documentation in German language, 2016]
Authors: Meischner V. , Laube B. , Hartwig A. ,   MAK Commission
Published: January 2016

MAK Value Documentation for 4‐Methyl‐3‐pentene‐2‐one

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated the maximum concentration at the work place (MAK value) for 4‐methyl‐3‐pentene‐2‐one of 5 ml/m
3
, considering local and systemic toxicity as well as developmental toxicity. As described in the last evaluation from 2006, 4‐methyl‐3‐pentene‐2‐one is irritating to eyes and skin. Starting at the lowest concentration of 31 ml/m
3
in a 49‐day‐inhalation‐study with daily exposure exudate in the olfactory epithelium is observed in 10 of 24 rats. A NAEC of 10 ml/m
3
is extrapolated. Since 2014, the Commission uses an empirical approach to set MAK values for substances with critical effects on the upper respiratory tract or the eyes. Taking into consideration exposure of rats took place 7 days a week and no chronic study is available, it is assumed, that the chronic NAEC is 5 ml/m
3
. As olfactory epithelium is the target tissue, according to the empirical approach, the MAK‐value is reduced to 2 ml/m
3
. The assignment to Peak Limitation Category I, because local effects are critical, and the excursion factor of 2 are confirmed. As there are no developmental toxicity studies, the assignment to Pregnancy Risk Group D is confirmed.
Dipropylenglykol [MAK Value Documentation in German language, 2016]
Authors: Michaelsen S. , Kreis P. , Bartsch R. , Roßbach B. , Bader M. , Hartwig A. ,   MAK Commission
Published: January 2016

MAK Value Documentation for Dipropylene glycol

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated the maximum concentration at the work place (MAK value) for dipropylene glycol has been set at 100 mg/m
3
for the inhalable fraction, considering the endpoints respiratory tract irritation and systemic toxicity as well as absorption through the skin. A 2‐year drinking water study with rats shows a NOAEL for focal inflammation of the liver in males of 115 mg/kg body weight and day and a NOAEL for olfactory epithelium degeneration in males and females of 470 and 530 mg/kg body weight and day, respectively. This raises the question, whether the olfactory epithelium could also be a local target tissue after inhalation. Inhalation studies with dipropylene glycol are not available. The substance shows very slight irritation of skin and eyes, if any. Thus, there are no indications of a potential local irritative effect to the upper airways. Therefore, the MAK value of 100 mg/m
3
derived from systemic effects is validated. As systemic effects are critical, the assignment to Peak Limitation Category II and the excursion factor of 2 are retained. A recent in‐vitro study with human skin shows that skin contact does not contribute significantly to systemic toxicity and the former designation with an “H” notation is withdrawn.
N‐Ethyl‐2‐pyrrolidon (Dampf) [MAK Value Documentation in German language, 2016]
Authors: Lohmann R. D. , Meischner V. , Leibold E. , Schriever‐Schwemmer G. , Hartwig A. ,   MAK Commission
Published: January 2016

MAK Value Documentation for N‐Ethyl‐2‐pyrrolidone

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated the maximum concentration at the work place (MAK value) of N‐ethyl‐2‐pyrrolidone of 2 ml/m
3
, considering the endpoints irritation of the respiratory tract and developmental toxicity.

The critical effect of N‐ethyl‐2‐pyrrolidone is degeneration of the olfactory epithelia in rats in a new 13‐week‐inhalation study. Since 2014, the Commission uses an empirical approach to set MAK values for substances with critical effects on the upper respiratory tract or the eyes. According to these proposals, the NOAEC of 62.6 mg/m
3
(13.3 ml/m
3
vapour) corresponds to a work place air concentration of 31 mg/m
3
(6.6 ml/m
3
). The irritating response in the 13 week study is not more pronounced than after shorter exposition times. Therefore the MAK‐value is increased to 5 ml/m
3
for the vapour phase only. Local effects are critical and only minimal irritation occurs at the LOAEC, therefore the assignment of N‐ethyl‐2‐pyrrolidone to Peak Limitation category I and excursion factor 2 established in 2014 are retained. Also with the increased MAK value, damage to the embryo or foetus is unlikely when the MAK value is observed. Therefore, classification of N‐ethyl‐2‐pyrrolidone in Pregnancy Risk Group C is confirmed.
Acetone [MAK Value Documentations, 2013]
Authors: Schriever-Schwemmer G. , Michaelsen S. , Greim H. , Hartwig A. ,   MAK Commission
Published: January 2016

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated the developmental toxicity of acetone. Available unpublished study reports and publications are described in detail. The maximum concentration at the work place (MAK value) of acetone is 500 ml/m
3
, based on the irritant effect and the state of health of volunteers.

In a development toxicity study after inhalation exposure no teratogenic effects were found in the mouse up to 6600 ml/m
3
. The diversity of malformations was increased at 11 000 ml/m
3
in the rat, and there was a linear trend for variations of asymmetric sternebrae and delayed ossifications of the sternum. Reduced foetal weights were found in both rats and mice. The NOAEC for developmental toxicity in rats and mice is 2200 ml/m
3
; the NAEC (no adverse effect concentration) could be even higher than 2200 ml/m
3
. As a greater diversity of malformations was observed in rat pups at concentrations that caused only slight maternal toxicity, and only a four‐fold margin lies between the NOAEC for developmental toxicity and the MAK value of 500 ml/m
3
, damage to the embryo or foetus cannot be excluded after exposure to concentrations at the level of 500 ml/m
3
and acetone is assigned to Pregnancy Risk Group B.

In view of the NOAEC for developmental toxicity of 2200 ml/m
3
, prenatal toxicity is not to be expected at acetone concentrations of about 200 ml/m
3
or below, corresponding to the definition of Pregnancy Risk Group C.
Phosphortrichlorid [MAK Value Documentation in German language, 2016]
Authors: Kreis P. , Bartsch R. , van Thriel C. , Brüning T. , Hartwig A. ,   MAK Commission
Published: January 2016

MAK Value Documentation for Phosphorus trichloride

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated the maximum concentration at the work place (MAK value) of phosphorus trichloride of 0.5 ml/m
3
, considering the endpoints local and systemic toxicity as well as developmental toxicity. Available publications are described in detail. As described in the previous evaluation of 2006, phosphorus trichloride is corrosive to eyes and skin and in a 28‐day‐inhalation‐study irritative to the respiratory tract of rats with a NOAEC of 3 ml/m
3
. Since 2014, the Commission uses an empirical approach to set MAK values for substances with critical effects on the upper respiratory tract or the eyes. According to this approach, a concentration of 0.17 ml/m
3
for the work place air can be calculated from this study. Therefore, the MAK value is lowered to 0.1 ml/m
3
. The assignment to Peak Limitation Category I, because local effects are critical, and the excursion factor of 1 are confirmed. A developmental toxicity study with phosphorus trichloride in rats shows that damage for the embryo or foetus is unlikely if the MAK‐value is observed, and the assignment to Pregnancy Risk Group C is retained.
Phosphorus, white/yellow [MAK Value Documentations, 2012]
Authors: Kreis P. , Bartsch R. , Rettenmeier A. W. , Bruning T. , Hartwig A. ,   MAK Commission
Published: January 2016

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated the maximum concentration at the work place (MAK value) of white/yellow phosphorus of 0.1 mg/m
3
and evaluated the MAK value of red phosphorus, considering all toxicity endpoints. Available unpublished study reports and publications are described in detail. Data is limited and no repeated dose studies are available for red phosphorus and it is assigned to Section II b of the List of MAK and BAT values. Inhalation studies in animals or humans are not available for white/yellow phosphorus. The systemic NOAEL in rats is 0.015 mg/kg body weight and day in a one‐generation study. Therefore, the MAK value is reduced to 0.05 mg/m
3
. Using a read‐across to the oxidation product phosphorus pentoxide or to phosphoric acid, one of the acids formed during oxidation in humid air, both with MAK values of 2 mg/m
3
, no irritant effects are expected for white/yellow phosphorus at 0.05 mg/m
3
. As the MAK value is based on a systemic effect, white/yellow phosphorus is reclassified in Peak Limitation Category II. No data are available from which a substance‐specific excursion factor could be derived, therefore the default excursion factor of 2 is assigned. No risk to the foetus is expected if the MAK value is observed. No data on sensitizing effects of white phosphorus are available. The only available genotoxicity data are negative mutagenicity tests in Salmonella typhimurium. Valid carcinogenicity studies are not available. No prolonged skin contact to white/yellow phosphorus is possible due to its burning and corrosive effects and owing to the poor water solubility of phosphorus, the calculated quantities penetrating through skin are not expected to contribute significantly to systemic toxicity.
Development and First Validation of a Disease Activity Score for Gout
Authors: Scirè Carlo A. , Carrara Greta , Viroli Cinzia , Cimmino Marco A. , Taylor William J. , Manara Maria , Govoni Marcello , Salaffi Fausto , Punzi Leonardo , Montecucco Carlomaurizio , Matucci‐Cerinic Marco , Minisola Giovanni ,   and the Study Group for the Kick‐Off of the Italian Network for Gout Study
Published: January 2016

Objective

To develop a new composite disease activity score for gout and provide its first validation.

Methods

Disease activity has been defined as the ongoing presence of urate deposits that lead to acute arthritis and joint damage. Every measure for each Outcome Measures in Rheumatology core domain was considered. A 3‐step approach (factor analysis, linear discriminant analysis, and linear regression) was applied to derive the Gout Activity Score (GAS). Decision to change treatment or 6‐month flare count were used as the surrogate criteria of high disease activity. Baseline and 12‐month followup data of 446 patients included in the Kick‐Off of the Italian Network for Gout cohort were used. Construct‐ and criterion‐related validity were tested. External validation on an independent sample is reported.

Results

Factor analysis identified 5 factors: patient‐reported outcomes, joint examination, flares, tophi, and serum uric acid (sUA). Discriminant function analysis resulted in a correct classification of 79%. Linear regression analysis identified a first candidate GAS including 12‐month flare count, sUA, visual analog scale (VAS) of pain, VAS global activity assessment, swollen and tender joint counts, and a cumulative measure of tophi. Alternative scores were also developed. The developed GAS demonstrated a good correlation with functional disability (criterion validity) and discrimination between patient‐ and physician‐reported measures of active disease (construct validity). The results were reproduced in the external sample.

Conclusion

This study developed and validated a composite measure of disease activity in gout. Further testing is required to confirm its generalizability, responsiveness, and usefulness in assisting with clinical decisions.
Improving Appropriate Access to Care With Central Referral and Triage in Rheumatology
Authors: Hazlewood Glen S. , Barr Susan G. , Lopatina Elena , Marshall Deborah A. , Lupton Terri L. , Fritzler Marvin J. , Mosher Dianne P. , Steber Whitney A. , Martin Liam
Published: January 2016

Objective

To evaluate the short‐term and long‐term impact of a centralized system for the intake and triage of rheumatology referrals on access to care and referral quality.

Methods

An innovative central referral process, the Central Referral and Triage in Rheumatology (CReATe Rheum) program, was implemented in 2006, serving a referral base of 2 million people. Referrals are received in a central office, triaged by trained nurses, and assigned to the next available appointment on a prioritized basis. To evaluate the short‐term impact, we compared wait times, duplicate referrals, and no‐shows from a pre‐implementation practice audit to a 2‐year post‐implementation evaluation (January 2007 to December 2008). Rheumatologists also assessed the quality and completeness of the referral information and accuracy of the urgency category assigned during triage. We evaluated the long‐term impact by tracking referral volume, wait times, and rheumatologist manpower each year until December, 2013.

Results

During the first 2 years, wait‐time variability between rheumatologists decreased, and wait times were reduced for moderate and urgent referrals. CReATe Rheum improved the quality of referral information and eliminated duplicate referrals. The urgency of the referral was assigned correctly in 90% of referrals. Over the long term, CReATe Rheum maintained short wait times for more urgent patients despite a growing number of referrals and a stable number of rheumatologists.

Conclusion

A centralized system for the intake and triage of rheumatology referrals improved referral quality, reduced system inefficiencies, and effectively managed wait times on a prioritized basis for a large referral population.
Observed Incidence of Uveitis Following Certolizumab Pegol Treatment in Patients With Axial Spondyloarthritis
Authors: Rudwaleit M. , Rosenbaum J. T. , Landewé R. , Marzo‐Ortega H. , Sieper J. , van der Heijde D. , Davies O. , Bartz H. , Hoepken B. , Nurminen T. , Deodhar A.
Published: January 2016

Objective

Axial spondyloarthritis (axial SpA) is characterized by inflammation of the spine and sacroiliac joints and can also affect extraarticular sites, with the most common manifestation being uveitis. Here we report the incidence of uveitis flares in axial SpA patients from the RAPID‐axSpA trial, including ankylosing spondylitis (AS) and nonradiographic (nr) axial SpA.

Methods

The RAPID‐axSpA (NCT01087762) trial is double‐blind and placebo‐controlled to week 24, dose‐blind to week 48, and open‐label to week 204. Patients were randomized to certolizumab pegol (CZP) or placebo. Placebo patients entering the dose‐blind phase were re‐randomized to CZP. Uveitis events were recorded on extraarticular manifestation or adverse event forms. Events were analyzed in patients with/without history of uveitis, and rates reported per 100 patient‐years.

Results

At baseline, 38 of 218 CZP‐randomized patients (17.4%) and 31 of 107 placebo‐randomized patients (29.0%) had past uveitis history. During the 24‐week double‐blind phase, the rate of uveitis flares was lower in CZP (3.0 [95% confidence interval (95% CI) 0.6–8.8] per 100 patient‐years) than in placebo (10.3 [95% CI 2.8–26.3] per 100 patient‐years). All cases observed during the 24‐week double‐blind phase were in patients with a history of uveitis; in these patients, rates were similarly lower for CZP (17.1 [95% CI 3.5–50.1] per 100 patient‐years) than placebo (38.5 [95% CI 10.5–98.5] per 100 patient‐years). Rates of uveitis flares remained low up to week 96 (4.9 [95% CI 3.2–7.4] per 100 patient‐years) and were similar between AS (4.4 [95% CI 2.3–7.7] per 100 patient‐years) and nr‐axial SpA (5.6 [95% CI 2.9–9.8] per 100 patient‐years).

Conclusion

The rate of uveitis flares was lower for axial SpA patients treated with CZP than placebo during the randomized controlled phase. Incidence of uveitis flares remained low to week 96 and was comparable to rates reported for AS patients receiving other anti–tumor necrosis factor antibodies.
Improving Charge Separation across a Hybrid Oxide/Polymer Interface by Cs Doping of the Metal Oxide
Authors: Sevinchan Yunus , Hopkinson Paul E. , Bakulin Artem A. , Herz Julia , Motzkus Marcus , Vaynzof Yana
Published: January 2016

The process of photoinduced charge carrier separation in hybrid optoelectronics remains only partially understood, with the mechanism behind creation and dissociation of bound charge pairs (BCPs) being open questions. To investigate these processes, the model hybrid ZnO/poly(3‐hexylthiophene) system is employed and it is shown that Cs doping of ZnO results in a decrease in the density of gap states at the metal oxide surface and, in turn, a reduction in the yield of BCPs. This provides direct experimental evidence for a previously proposed model of BCP creation by electron trapping at the metal oxide surface states. Furthermore, Cs doping is found to substantially increase the open circuit voltage in these devices without the negative effects on the short circuit current which were observed in studies with other dopants. This offers new possibilities for hybrid photovoltaic devices with increased power conversion efficiencies and provides valuable insights on the charge separation processes in hybrid organic–inorganic photovoltaics.
Multi‐stage adjustable robust optimization for process scheduling under uncertainty
Authors: Lappas Nikolaos H. , Gounaris Chrysanthos E.
Published: January 2016

Variations in parameters such as processing times, yields, and availability of materials and utilities can have a detrimental effect in the optimality and/or feasibility of an otherwise “optimal” production schedule. In this article, we propose a multi‐stage adjustable robust optimization approach to alleviate the risk from such operational uncertainties during scheduling decisions. We derive a novel robust counterpart of a deterministic scheduling model, and we show how to obey the observability and non‐anticipativity restrictions that are necessary for the resulting solution policy to be implementable in practice. We also develop decision‐dependent uncertainty sets to model the endogenous uncertainty that is inherently present in process scheduling applications. A computational study reveals that, given a chosen level of robustness, adjusting decisions to past parameter realizations leads to significant improvements, both in terms of worst‐case objective as well as objective in expectation, compared to the traditional robust scheduling approaches. © 2016 American Institute of Chemical Engineers AIChE J, 62: 1646–1667, 2016
Reduced lung function in smokers in a lung cancer screening cohort with asbestos exposure and pleural plaques
Authors: Lopatin Sarah , Tsay Jun‐Chieh , Addrizzo‐Harris Doreen , Munger John S. , Pass Harvey , Rom William N.
Published: January 2016

Background

While low dose computed tomography (LDCT) screening for lung cancer is recommended for high‐risk smokers, ages 55–74 years, information about asbestos exposure may not be routinely elicited. Asbestos exposure is associated with declining respiratory function over time; however, the effect of a history of asbestos exposure in LDCT screening cohorts is limited. We report the relationship between asbestos exposure and pulmonary function in a cohort of heavy smokers with a history of occupational asbestos exposure, hypothesizing that these subjects will have additional decreased pulmonary function. We also examined relationships between spirometric measurements and the presence of isolated pleural plaques.

Methods

A cross‐sectional study was performed using data from the NYU Lung Cancer Biomarker Center cohort to compare study subjects with a history asbestos exposure primarily in the period since 1970 when tighter federal standards were in place (n = 359) to those without asbestos exposure (n = 1038) with respect to pulmonary function, LDCT lung imaging findings, and clinical symptoms. We further classified individuals with asbestos exposure by length of exposure time to examine the effect of duration of exposure on pulmonary function. Lastly, for asbestos‐exposed participants, we examined the association of spirometric measurements with the presence of absence of isolated pleural plaques.

Results

Individuals with asbestos exposure had decreased FVC % predicted compared to those with no asbestos exposure (76% vs. 85% predicted, P < 0.01) and FEV1 % predicted (64% vs. 67% predicted, P < 0.01). Since there was no change in FEV1/FVC ratio, the findings are consistent with restrictive impairment. Those with ≥20 years of exposure had a lower mean FVC % predicted compared to those with less than 20 years of exposure (74% vs. 78% predicted, P = 0.017). Individuals with asbestos exposure were more likely to have pleural plaques (P < 0.001) on CT. Those with isolated pleural plaques had lower mean % predicted FEV1 (P = 0.005) and FVC (P = 0.001) compared to those without pleural plaques.

Conclusions

Occupational asbestos exposure in a cohort of heavy smokers was associated with a significant restrictive decline in pulmonary function, with longer duration of exposure associated with greater decline. The presence of isolated pleural plaques was also associated with reduced lung function. Am. J. Ind. Med. 59:178–185, 2016. © 2016 Wiley Periodicals, Inc.
Paternal kin recognition and infant care in white‐faced capuchins (Cebus capucinus)
Authors: Sargeant Elizabeth J. , Wikberg Eva C. , Kawamura Shoji , Jack Katharine M. , Fedigan Linda M.
Published: January 2016

Evidence for paternal kin recognition and paternally biased behaviors is mixed among primates. We investigate whether infant handling behaviors exhibit paternal kin biases in wild white‐faced capuchins monkeys (Cebus capucinus)by comparing interactions between infants and genetic sires, potential sires, siblings (full sibling, maternal, and paternal half‐siblings) and unrelated handlers. We used a linear mixed model approach to analyze data collected on 21 focal infants from six groups in Sector Santa Rosa, Costa Rica. Our analyses suggest that the best predictor of adult and subadult male interactions with an infant is the male's dominance status, not his paternity status. We found that maternal siblings but not paternal siblings handled infants more than did unrelated individuals. We conclude that maternal but not paternal kinship influence patterns of infant handling in white‐faced capuchins, regardless of whether or not they can recognize paternal kin. Am. J. Primatol. 78:659–668, 2016. © 2016 Wiley Periodicals, Inc.
Examining biological continuity across the late holocene occupation of the aleutian islands using cranial morphometrics and quantitative genetic permutation
Authors: Maley Blaine
Published: January 2016

Objectives

The number of distinct human migrations into the Aleutian Islands during the Holocene has been a recurrent debate in the anthropological literature. Stemming from Hrdlička's sorting of the prehistoric remains into two distinct populations based on archaeological context and cranial measurements, the human occupation of the Aleutian Islands has long been thought to be the consequence of two distinct human migrations, a Paleo‐Aleut migration that provided the initial settlement of the islands, and a Neo‐Aleut migration that replaced the original settlers around 1000 BP. This study examines the relationship of the Aleut cranial assemblages in the context of greater Alaskan population variability to assess the evidence for a substantial migration into the Aleutian Islands during the late Holocene.

Materials and Methods

A battery of 29 cranial measurements that quantify global cranial shape were analyzed using Euclidean morphometric methods and quantitative genetic permutation methods to examine the plausibility for two distinct Aleut occupations (“Paleo‐Aleut” and “Neo‐Aleut”), the latter of which is held to share closer phenetic affinities to mainland Alaskan populations than the former. The Aleut skeletal assemblages were arranged according to temporal association, geographic location, and cranial typology, and analyzed within a comparative framework of mainland Alaskan samples using principal coordinates, biological distance and random skewers permutation methods.

Results

Regardless of how the Aleut assemblages are divided, they show greater similarity to each other than to any of the mainland Alaskan assemblages. These findings are consistent across the methodological approaches.

Discussion

The results obtained in this study provide no support for a cranial morphology‐based subdivision of the Aleuts into two distinct samples, Hence, there is no evidence for a substantial population migration of so‐called Neo‐Aleuts, nor for a population replacement event of an extant Paleo‐Aleut population by a mainland‐affiliated Neo‐Aleuts population at or after 1000 BP. Am J Phys Anthropol 160:71–85, 2016. © 2016 Wiley Periodicals, Inc.
Metabolic crisis occurs with seizures and periodic discharges after brain trauma
Authors: Vespa Paul , Tubi Meral , Claassen Jan , Buitrago‐Blanco Manuel , McArthur David , Velazquez Angela G. , Tu Bin , Prins Mayumi , Nuwer Marc
Published: January 2016

Objective

Traumatic brain injury (TBI) results in persistent disruption of brain metabolism that has yet to be mechanistically defined. Early post‐traumatic seizures are one potential mechanism for metabolic crisis and hence could be a therapeutic target. We hypothesized that seizures and pseudoperiodic discharges (PDs) may be mechanistically linked to metabolic crisis as measured by cerebral microdialysis.

Methods

A prospective multicenter study of surface and intracortical depth electroencephalography (EEG) was performed in conjunction with cerebral microdialysis in a cohort of severe TBI patients with time‐locked analysis of the neurochemical response to seizures and pseudoperiodic discharges.

Results

Seizures or PDs occurred in 61% of 34 subjects, with 42.9% of these seizures noted only on intracortical depth EEG and in some cases lasting for many hours. Metabolic crisis as measured by elevated cerebral microdialysis lactate/pyruvate ratio occurred during seizures or PDs but not during electrically nonepileptic epochs.

Interpretation

In TBI patients, seizures and periodic discharges are one mechanism for metabolic crisis, and hence represent a therapeutic target for future study. Ann Neurol 2016;79:579–590
Design of highly tough poly(l‐lactide)‐based ternary blends for automotive applications
Authors: Bouzouita Amani , Samuel Cédric , Notta‐Cuvier Delphine , Odent Jérémy , Lauro Franck , Dubois Philippe , Raquez Jean‐Marie
Published: January 2016

Technical renewable poly(l‐lactide) (PLA)‐based blends represent an elegant way to achieve attractive properties for engineering applications. Recently, the miscibility between PLA and poly(methyl methacrylate) (PMMA) gave rise to new formulations with enhanced thermo‐mechanical properties but their high brittleness still remains a challenge to be overcome. This work here focuses on rubber‐toughened PLA/PMMA formulations for injection‐molding processes upon the addition of a commercially available ethylene‐acrylate impact modifier (BS). The miscibility between PLA and PMMA is not altered by the presence of BS but the incorporation of BS (17% by weight) into a PLA/PMMA matrix could enhance both ductility and toughness of PLA/PMMA blends for PMMA content up to 50 wt %. An optimum range of particle sizes (dn ∼0.5 µm) of the dispersed domains for high impact toughness is identified. These bio‐based ternary blends appear as promising alternatives to petro‐sourced blends such as ABS‐based blends in engineering injection‐molding parts. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 43402.
Synthesis and characterization of cetirizine‐containing, pH‐sensitive acrylic acid/poly(vinyl alcohol) hydrogels
Authors: Ranjha Nazar Mohammad , Hanif Muhammad , Naz Aqsa , Shah Muhammad Shahid , Abbas Ghulam , Afzal Zunaira
Published: January 2016

In this study, interpenetrated acrylic acid (AA)/poly(vinyl alcohol) (PVA) hydrogels were prepared by free‐radical polymerization with N,N‐methylene bisacrylamide (MBAAm) as a crosslinker. The basic structural parameters, such as the molecular weight between crosslinks, volume interaction parameter, number of crosslinks, Flory–Huggins solvent interaction parameter, and diffusion coefficient, were calculated. Cetirizine dihydrochloride was loaded as a model drug in selected samples. The prepared hydrogels were evaluated for swelling, sol–gel fraction, and porosity. The swelling of the AA/PVA hydrogels was found to be directly proportional to the pH, that is, 1.2–7.5, depending on composition. The percentage of cetirizine hydrochloride was found to be directly proportional to the buffer pH and was at its maximum at pH 7.5, that is, 90–95%, and its lowest at pH 1.2, that is, 20–30%. The gel fraction increased with increasing concentration of AA and MBAAm, whereas the porosity showed the same response with AA, but an inverse relationship was observed with MBAAm. The drug‐release data were fitted into various kinetics models, including the zero‐order, first‐order, Higuchi, and Peppas models, which showed non‐Fickian diffusion. The prepared hydrogels were characterized by Fourier transform infrared spectroscopy and scanning electron microscopy, and no interaction was found among the polymer ratio and the drug. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 43407.
Graft copolymerization of methyl methacrylate from brominated poly(isobutylene‐co‐isoprene) via atom transfer radical polymerization
Authors: Wang Jinyuan , Wan Chaoying , Zhang Yong , Zhai Yinghao , Song Shiqiang , Ren Wentan , Peng Zonglin
Published: January 2016

Commercial brominated poly(isobutylene‐co‐isoprene) (BIIR) rubber has been directly used for the initiation of atom transfer radical polymerization (ATRP) by utilizing the allylic bromine atoms on the macromolecular chains of BIIR. The graft copolymerization of methyl methacrylate (MMA) from the backbone of BIIR which was used as a macroinitiator was carried out in xylene at 85 °C with CuBr/N,N,N′,N″,N″‐pentamethyldiethylenetriamine as a catalytic complex. The polymerization conditions were optimized by adjusting the catalyst and monomer concentration to reach a higher monomer conversion and meanwhile suppress macroscopic gelation during the polymerization process. This copolymerization followed a first‐order kinetic behavior with respect to the monomer concentration, and the number‐average molecular weight of the grafted poly(methyl methacrylate) (PMMA) increased with reaction time. The resultant BIIR‐graft‐PMMA copolymers showed phase separation morphology as characterized by atomic force microscopy, and the presence of PMMA phase increased the polarity of the BIIR copolymers. This study demonstrated the feasibility of using commercial BIIR polymer directly as a macromolecular initiator for ATRP reactions, which opens more possibilities for BIIR modifications for wider applications. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 43408.
Preparation and properties of polyvinyl chloride ultrafiltration membranes blended with functionalized multi‐walled carbon nanotubes and MWCNTs/Fe3O4 hybrids
Authors: Wang Caihong , Wu Hao , Qu Fangshu , Liang Heng , Niu Xiaojun , Li Guibai
Published: January 2016

To investigate the influence of magnetic materials combined with carbon nanotubes (CNTs) as fillers on the membrane properties, multi‐walled carbon nanotubes (MWCNTs) functionalized by mixed acids (VH2SO4:VHNO3=3:1) were loaded by Fe3O4 through a hydrothermal method. The obtained MWCNTs/Fe3O4 hybrids were characterized by X‐ray diffraction (XRD), Infrared spectroscopy (IR) spectrum, and scanning electron microscope (SEM) and then blended with polyvinyl chloride (PVC) to prepare ultrafiltration (UF) membranes through a phase inversion process. Simultaneously, two other UF membranes, PVC blended with acid‐treated MWCNTs and PVC blended with nothing, were also prepared. The results showed that the membrane porosity and mean pore size increased slightly with the addition of fillers. Static contact angle showed that MWCNTs/Fe3O4 hybrids improved the hydrophilicity of membrane surface better than the acid‐treated MWCNTs. Pure water flux increased consistently with the hydrophilicity of the membrane surface. SEM and atomic force microscope (AFM) images showed that the MWCNTs/Fe3O4 blended membrane formed a relatively complete pore structure throughout the cross‐section and had a rougher top surface. However, the mechanical properties of membranes with fillers were reduced compared with the pristine PVC membrane. The rejections of membranes for Bovine serum albumin (BSA), Bisphenol A (BPA), and Norfloxacin (NOR) showed that MWCNTs/Fe3O4 played an important role in trapping pollutants in membrane filtration. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 43417.
In situ compatibilization of polylactide/thermoplastic polyester elastomer blends using a multifunctional epoxide compound as a processing agent
Authors: Wang Sisi , Pang Sujuan , Xu Nai , Pan Lisha , Lin Qiang
Published: January 2016

In situ compatibilized poly(lactic acid)/thermoplastic polyester elastomer (PLA/TPEE) (80/20) blends are prepared by using multifunctional epoxide oligomer (coded as ADR) as a reactive modifier. Experiments such as torque, melt mass flow rate (MFR), SEM, DSC and tensile test were conducted to characterize properties of the PLA/TPEE/ADR blends. In situ reactions between PLA, TPEE and ADR were researched using a lab torque rheometer. It was proposed that ADR may initiate a variety of chain extension/branching reactions between PLA and TPEE under mixing process. In particular, the formed copolymer PLA‐ADR‐TPEE could be viewed as an in situ compatibilizer to improve the compatibility of PLA and TPEE. As expected, the value of MFR decreased greatly with increasing the ADR addition. The morphology reveals that interface adhesion of PLA/TPEE blend was enhanced with the incorporation of ADR, which led to a reduction in TPEE domain size. Moreover, tensile ductility of PLA/TPEE (80/20) blend was improved greatly by addition of the reactive modifier, e.g. the elongation at break was increased from 53% to the maximum value of 213% with addition of 1.2 phr ADR. The toughening effect can be explained by crazing with shear yielding mechanism. Attempts were made to produce ductile films from these PLA/TPEE/ADR blends by using extrusion blowing method. Effect of ADR on blowing stability and tensile property of these blends was investigated. Improvement on blowing stability and tensile ductility of PLA/TPEE/ADR films also shows that ADR is an efficiently reactive compatibilizer, as well as a viscosity enhancer for PLA/TPEE blends. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 43424.
Ordered mesoporous carbon preparation by the in situ radical polymerization of acrylamide and its application for resorcinol removal
Authors: Shou Wan , Chao Bing , Ahmad Zaki Uddin , Gang Daniel Dianchen
Published: January 2016

In this study, acrylamide (AM) was, for the first time, successfully used to synthesize ordered mesoporous carbon (OMC) through in situ polymerization inside SBA‐15 (Santa Barbara Amorphous type material) as a hard template. A straightforward and environmentally friendly method was proposed and verified with an emphasis on the precursor modification for the preparation of OMC. The influences of the structure and the amount of SBA‐15 on the OMC structure and adsorption capacity were evaluated. To improve the adsorption capacity and yield, the following three approaches were tried: (1) the use of concentrated sulfuric acid (H2SO4) to fix carbon and nitrogen, (2) the use of a crosslinking agent, and (3) the addition of melamine as a possible nitrogen source. The adsorption capacities for resorcinol were evaluated, and they showed an improvement of 37% in comparison with that of the commercially available granular activated carbon (27 mg/g). Well‐OMC materials were obtained with higher yields with H2SO4 and crosslinking agent compared with those obtained for the pure AM precursor. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 43426.
The thermal, optical, flame retardant, and morphological consequence of embedding diacid‐capped ZnO into the recycled PET matrix
Authors: Mallakpour Shadpour , Javadpour Mashal
Published: January 2016

We extended our work to a fast and facile nanocomposites (NCs) manufacturing by incorporation of ZnO nanoparticles (NPs) on to a recycled poly(ethylene terephthalate) PET as a polymer matrix prepared by a dissolution/reprecipitation method. The surface of ZnO NPs was functionalized with synthesized optically active diacid containing alanine amino acid. Organo‐modified NPs which provided using solution blending technique through ultrasonic irradiation, were embedded into recycled PET. PET@ZnO/DA NCs containing different loadings of functionalized NPs (1, 3, 5 wt %) were investigated by thermal gravimetric analysis, field emission scanning electron microscopy, transmission electron microscopy, X‐ray diffraction, Fourier transform infrared spectroscopy and UV–visible spectroscopy. Morphological studies revealed uniformly dispersed ZnO/DA NPs in the polymer matrix. The crystalline nature of PET slightly improved as a function of the NPs concentration. Char yield in TGA and LOI values indicated that the obtained NCs were capable of exhibiting flame retardant properties. The NCs were found to exhibit more absorbance in the UV and visible region in compare to the neat PET. The effect of ultrasonication in different solvent on the morphology of the recycled polymer particle was also studied. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 43433.
Risk of End‐Stage Renal Disease in Patients With Lupus Nephritis, 1971–2015: A Systematic Review and Bayesian Meta‐Analysis
Authors: Tektonidou Maria G. , Dasgupta Abhijit , Ward Michael M.
Published: January 2016

Objective

End‐stage renal disease (ESRD) is a major consequence of lupus nephritis, but how this risk has changed over time is unknown. We conducted this systematic review to examine changes in ESRD among adults with lupus nephritis from 1971 to 2015 and to estimate risks of ESRD among contemporary patients.

Methods

We searched PubMed, Embase, and the Cochrane Database of Systematic Reviews for cohort studies and clinical trials on ESRD in adults with lupus nephritis. We analyzed studies from developed and developing countries separately. The outcome was probability of ESRD at 5, 10, and 15 years of lupus nephritis.

Results

We included 187 articles that reported on 18,309 patients. In developed countries, the 5‐year risk of ESRD decreased from 16% (95% confidence interval [95% CI] 14–17%) in 1970–1979 to 11% (95% CI 10–12%) in the mid‐1990s and then plateaued. ESRD risks at 10 years and 15 years showed steeper declines in the 1970s and 1980s but also plateaued in 1993–1997, with a notable increase in the late 2000s. The decrease in risk after 1980 coincided with increased use of cyclophosphamide. The 15‐year ESRD risk was higher in developing countries than in developed countries. Patients with class IV lupus nephritis had the greatest risk of ESRD, with a 15‐year risk of 44% during the 2000s.

Conclusion

Risks of ESRD in lupus nephritis improved between the 1970s and the mid‐1990s and then plateaued, with an increase in the late 2000s. This pattern suggests limitations in the effectiveness of, or access to, current treatments.
Incidence of Severe Infections and Infection‐Related Mortality During the Course of Giant Cell Arteritis: A Multicenter, Prospective, Double‐Cohort Study
Authors: Schmidt J. , Smail A. , Roche B. , Gay P. , Salle V. , Pellet H. , Duhaut P.
Published: January 2016

Objective

To assess the incidence of infections leading to hospitalization, the mortality rate related to infections, and the determinants of these factors in patients with giant cell arteritis (GCA).

Methods

In total, 486 patients with GCA (75% women) were enrolled at the time of diagnosis. All patients fulfilled the American College of Rheumatology criteria for GCA. As controls, age‐ and sex‐matched subjects were randomly selected from the general population and matched to patients at the time of diagnosis of GCA. Both groups were prospectively followed up over a 5‐year period.

Results

Severe infections were more frequent among patients with GCA during the first year after diagnosis, compared to general population controls (incidence rate ratio 2.1, 95% confidence interval [95% CI] 1.2–3.4; incidence rate 11.1/100 patient‐years [95% CI 8.3–14.6] in patients with GCA versus 5.9/100 patient‐years [95% CI 4–8.4] in controls). Specifically, septic shock and infectious colitis were more frequent among the patients with GCA. Mortality caused by infections was higher in patients with GCA compared to controls (P < 0.0001 by log rank test). In analyses adjusted for age, among patients with GCA, a diagnosis of diabetes (hazard ratio [HR] 3.3, 95% CI 1.4–7.7) and a corticosteroid dosage that was >10 mg/day after 12 months of treatment (HR 4.61, 95% CI 1.38–15.36) were associated with death attributed to severe infection. The observed overall incidence of mortality was increased in patients with GCA during the early period of enrollment in the study (before 1997) (P = 0.0001 by log rank test), but thereafter was the same as that in the general population controls.

Conclusion

Frequencies of severe infections and rates of infection‐related mortality are increased during the first year after the diagnosis of GCA. The risk of infection increases in GCA patients with older age or in the presence of diabetes, or is greater when the dosage of corticosteroids has been increased to >10 mg/day after 12 months of treatment.
Regulation of Effector Treg Cells in Murine Lupus
Authors: Chandrasekaran Uma , Yi Woelsung , Gupta Sanjay , Weng Chien‐Huan , Giannopoulou Eugenia , Chinenov Yurii , Jessberger Rolf , Weaver Casey T. , Bhagat Govind , Pernis Alessandra B.
Published: January 2016

Objective

Treg cells need to acquire an effector phenotype to function in settings of inflammation. Whether effector Treg cells can limit disease severity in lupus is unknown. Interferon regulatory factor 4 (IRF‐4) is an essential controller of effector Treg cells and regulates their ability to express interleukin‐10 (IL‐10). In non–Treg cells, IRF‐4 activity is modulated by interactions with DEF‐6 and its homolog switch‐associated protein 70 (SWAP‐70). Although mice lacking both DEF‐6 and SWAP‐70 (double‐knockout [DKO] mice) develop lupus, they display normal survival, suggesting that in DKO mice, Treg cells can moderate disease development. The purpose of this study was to investigate whether Treg cells from DKO mice have an increased capacity to become effector Treg cells due to the ability of DEF‐6 and SWAP‐70 to restrain IRF‐4 activity.

Methods

Treg cells were evaluated by fluorescence‐activated cell sorting. The B lymphocyte–induced maturation protein 1 (BLIMP‐1)/IL‐10 axis was assessed by crossing DKO mice with BLIMP‐1‐YFP‐10BiT dual‐reporter mice. Deletion of IRF‐4 in Treg cells from DKO mice was achieved by generating FoxP3CreIRF‐4fl/fl DKO mice.

Results

The concomitant absence of DEF‐6 and SWAP‐70 led to increased numbers of Treg cells, which acquired an effector phenotype in a cell‐intrinsic manner. In addition, Treg cells from DKO mice exhibited enhanced expression of the BLIMP‐1/IL‐10 axis. Notably, DKO effector Treg cells survived and expanded as disease progressed. The accumulation of Treg cells from DKO mice was associated with the up‐regulation of genes controlling autophagy. IRF‐4 was required for the expansion and function of effector Treg cells from DKO mice.

Conclusion

This study revealed the existence of mechanisms that, by acting on IRF‐4, can fine‐tune the function and survival of effector Treg cells in lupus. These findings suggest that the existence of a powerful effector Treg cell compartment that successfully survives in an unfavorable inflammatory environment could limit disease development.