bluuebunny/crossref_metadata_2025 huggingface dataset:
Inconclusive Innovation “Returns”: A Meta‐Analysis of Research on Innovation in New Product Development*
Authors: Calantone Roger J. , Harmancioglu Nukhet , Droge Cornelia
Published: October 2010

This research on studies that have empirically examined the construct innovation provides a meta‐analysis of the marketing, management, and new product literatures. The study extends previous meta‐analytic works by drawing on 70 independent samples from 64 studies (published from 1970 to 2006) with a total sample size of 12,921. The overall objective is to propose a synthesized model that includes technological turbulence, market turbulence, customer orientation, competitor orientation, organizational structure, innovation, and new product performance. Six baseline hypotheses were developed and tested. The goal is not only to derive empirical generalizations from these literatures but also to investigate sources of inconsistencies in the findings. Four substantive and two methodological artifacts were tested to determine whether they moderate model relationships (i.e., whether the effect sizes differ for any of the six baseline hypotheses). The potential moderators were project versus program level of analysis, the nature of change required by the innovation, service versus product, country of the data's origin, continuous versus categorical measurement, and the number of scales used. From a theoretical perspective, the results corroborated the resource‐based view framework regarding the determinants and the performance outcome of innovation. New product performance (the performance outcome) is a direct consequence of innovation, and this effect is stronger when the data are collected from Western countries. This relationship holds regardless of whether the level of analysis is the new product program versus project or whether the innovation is a product or a service, a robust result relevant to researchers and managers alike. As for the determinants of innovation, the results were as follows. While market turbulence is overall not a direct antecedent to innovation, technological turbulence is overall positively related (especially when market discontinuities are considered or when the data are collected from Asian countries). Customer orientation encourages new product innovation overall, but especially at the program (as opposed to project) level in Western countries. The effect of competitor orientation is also positive. The results for either orientation construct or either turbulence construct held whether the level of analysis was project versus program or whether services versus products were examined. However, the relationship of mechanistic organizational structures to innovation, although positive in the overall sample, did vary by product (positive) versus service (negative).
Fostering Innovation in Complex Product Development Settings: The Role of Team Member Identity and Interteam Interdependence*
Authors: Glynn Mary Ann , Kazanjian Robert , Drazin Robert
Published: October 2010

Much of the existing research on innovation has concentrated on the study of individuals in small group settings. However, projects marked by multiple teams, high task interdependence, long duration, and large scale have become increasingly common in practice. Very little is known about how extant research findings related to innovation may generalize to such complex settings. Taking a multilevel theoretical approach, individuals' propensity to innovate is hypothesized as the product of individuals' relationship with their work team (team member identification) and their team's relationship to other teams within the organizational system (interteam interdependence). A large, diversified manufacturing firm engaged in a multibillion dollar project that involved the development of a technologically intense, highly innovative, new product served as the research site. Based on archival and survey data (n=118), five hypotheses were tested. The findings indicate that individuals' strong team identification and their perceptions of high interteam interdependence each had positive main effects on individuals' intentions to innovate. However, these two variables also interacted negatively to significantly decrease innovation intentions. Therefore, high identification with team may lead individuals to view interdependence with another team as a threat deflecting attention from innovation. The finding related to the role of identity, although consistent with work linking identity to other team behaviors, usefully broadens the reach of identification theories to demonstrate their impact on innovation. Additionally, this study is the first to demonstrate the impact of interteam interdependence on innovation. The alternative operationalizations of interdependence used in this paper highlight the fact that it must be strongly perceived and experienced by individuals to affect their innovation attitudes. The findings of this study also have implications for managerial practice in complex project settings. Since team identification has a direct effect on innovation, managers might employ strategies related to the creation of social bonds to complement task related connections among team members. Further, managers should configure staffing and incentive mechanisms to reinforce team identification. Finally, the results suggest that managers need to carefully attend to individuals' perceptions of each team's interdependence with other teams. Although perceptual interdependence can be an enabler of innovation, it can also be a disabler, through its interaction with team identification. Recognizing this potential for negative effects, managers might emphasize the benefits that can come from cooperating across teams, thus encouraging team members to identify not only at the team level but at the overall project level as well. Such actions might deflect negative identity threats that can derail positive innovation intentions.
Procedural Justice Climate in New Product Development Teams: Antecedents and Consequences
Authors: Akgün Ali E. , Keskin Halit , Byrne John C.
Published: October 2010

With the increasing interest in the concept of justice in the group behavior literature, the procedural justice (PJ) climate attracts many researchers and practitioners from different fields. Nevertheless, the PJ climate is rarely addressed in the new product development (NPD) project team literature. Specifically, the technology and innovation management (TIM) literature provides little about what the PJ climate is, its nature and benefits, and how it works in NPD project teams. Also, few studies investigate the antecedents and consequences of the PJ climate in NPD teams enhancing the understanding of this concept from a practical perspective. This paper discusses the PJ climate theory in a NPD team context and empirically demonstrates how team members' positive collective perceptions of a PJ climate can be developed and how a PJ climate influences a project's performance in NPD teams. In particular, team culture values including employee orientation, customer orientation, systematic management control, innovativeness, and social responsibility were investigated as antecedents, and team learning, speed to market, and market success of new products were studied as outcomes of PJ climate in this paper. By studying 83 NPD project teams it was found on the basis of using partial least squares (PLS) method that (1) the level of employee, customer and innovativeness orientation as well as systematic management control during the project had a positive impact on developing a PJ climate in an NPD team; (2) a PJ climate positively affects team learning and product development time (i.e., speed to market); and (3) team learning and speed to market mediate the relations between the PJ climate and new product success (NPS). Based on the findings, this paper suggests that managers should enhance the PJ climate and team culture in the project team to enhance team learning and to develop products faster. In particular, managers should (1) open a discussion forum among people and create a dialogue for people who disagree with the other project team members rather than dictating or emposing others ideas to them, (2) facilitate information searching and collecting mechanisms to make decisions effectively and to clarify uncertainties, and (3) allow team members to challange project‐related ideas and decisions and modify them with consensus. Also, to enhance the PJ climate during the project, managers should (1) respect and listen to all team members' ideas and try to understand why they are sometimes in opposition, (2) define team members' task boundaries and clarify project norms and project goals, and (3) set knowledge‐questioning values by facilitating team members to try out new ideas and seek out new ways to do things.
Relationship between Resting Electrocardiographic Parameters and Estimated 10‐Year Risk for Coronary Heart Disease in Healthy Adults in the USA
Authors: Lee Jong‐Min , Yoo Ki‐Dong , Oh Yong‐Seog , Kim Dong‐Bin , Park Chan‐Seok , Jang Sung‐Won , Kim Ji‐Hoon , Ihm Sang‐Hyun , Kim Hee‐Yeol , Lee Man‐Young , Seung Ki‐Bae , Rho Tai‐Ho
Published: October 2010

Background: Little is known about the relationship between resting electrocardiogram (ECG) parameters and the incidence of coronary heart disease (CHD). We sought to establish the association between ECG parameters and estimated 10‐year risk for CHD.

Methods: We applied the risk prediction algorithm used by the National Cholesterol Education Program Adult Treatment Panel III guidelines to data from 6399 individuals in the Third National Health and Nutrition Examination Survey (aged 40–79 years) who had sinus rhythm, no previous heart disease, and no evidence of prior myocardial infarction according to the 12‐lead Minnesota Code. We used multiple linear and logistic regression models to determine the relationship between 10‐year risk for CHD and levels of resting ECG parameters.

Results: After adjusting for age, gender, race, and body mass index, individuals with high risk had higher heart rate (HR), left ventricular mass index (LVMI), and cardiac infarction injury score (CIIS), and longer HR‐corrected QT (QTc) interval than those with low risk. In models fully adjusted for coronary risk factors, individuals in the highest quintile of HR, PR, and QTc interval were 2.2, 0.7, and 1.8 times, respectively, more likely to have a high 10‐year risk as those in the lowest quintiles. There are dose‐dependent associations between HR, LVMI, CIIS, and QTc interval and the 10‐year risk group.

Conclusions: These findings indicate that high HR, LVMI, and CIIS and prolonged QTc interval are positively and prolonged PR interval is negatively associated with high 10‐year risk for CHD in a general population.

Ann Noninvasive Electrocardiol 2010;15(4):315‐320
Spontaneous Fluctuations between Diagnostic and Nondiagnostic ECGs in Brugada Syndrome Screening: Portuguese Family with Brugada Syndrome
Authors: Santos Luis Ferreira dos , Correia Emanuel , Rodrigues Bruno , Nunes Luis , Costa António , Carvalho José Lopes , Elvas Luis , Henriques Carla , Matos Ana , Santos Jorge Oliveira
Published: October 2010

Background: All family members of patients with Brugada syndrome (BS) should be screened. Fluctuations between diagnostic and nondiagnostic electrocardiogram (ECG) patterns in patients with BS are recognized, but systematic studies are lacking. The objective of this work was to prospectively evaluate the spontaneous changes between diagnostic and nondiagnostic ECG patterns in a family screened for BS.

Methods: One hundred twenty‐nine family members were possibly affected plus the index case were screened with two ECGs with an interval of 6 months. Only coved‐type ECG pattern was defined as diagnostic; type 2 and 3 ECGs were considered suggestive.

Results: The first ECG series made six diagnostics and the second 11, but only three patients maintained the diagnostic ECG. Patients with basal diagnostic ECG were older and more frequently symptomatic. Body mass index (BMI) was significantly lower in adults with diagnostic plus suggestive ECG when compared with the others. No significant gender difference was found among relatives with or without diagnostic ECG.

Conclusion: Spontaneous phenotypic manifestation of BS was more frequent in older symptomatic patients, absent in children, and related with low BMI. ECG manifestations were intermittent in more than 3/4 of the affected patients. Fluctuations between diagnostic and nondiagnostic ECGs may have an implication on the correct phenotyping in family screening so several ECGs with drug challenging are mandatory.

Ann Noninvasive Electrocardiol 2010;15(4):337‐343
Subtraction Magnetocardiogram for Detecting Coronary Heart Disease
Authors: Kandori Akihiko , Ogata Kuniomi , Miyashita Tsuyoshi , Takaki Hiroshi , Kanzaki Hideyuki , Hashimoto Syuji , Shimizu Wataru , Kamakura Shiro , Watanabe Shigeyuki , Aonuma Kazutaka
Published: October 2010

Background:A large‐scale magnetocardiogram (MCG) database was produced, and standard MCG waveforms of healthy patients were calculated by using this database. It was clarified that the standard MCG waveforms are formed with the same shape and current distribution in healthy patients. A new subtraction method for detecting abnormal ST‐T waveforms in coronary heart disease (CHD) patients by using the standard MCG waveform was developed.

Methods:We used MCGs of 56 CHD patients (63 ± 3 years old) and 101 age‐matched normal control patients (65 ± 5 years old). To construct a subtracted ST‐T waveform, we used standard MCG waveforms produced from 464 normal MCGs (male: 268, female: 196). The standard MCG waveforms were subtracted from each subject's measured MCGs, which were shortened or lengthened and normalized to adjust to the data length and magnitude of the standard waveform. We evaluated the maximum amplitude and maximum current‐arrow magnitude of the subtracted ST‐T waveform.

Results:The maximum magnetic field, maximum magnitude of current arrows, and maximum magnitude of total current vector increased according to the number of coronary artery lesions. The sensitivity and specificity of detecting CHD and normal control patients were 74.6% and 84.1%, respectively.

Conclusions:The subtraction MCG method can be used to detect CHD with high accuracy, namely, sensitivity of 74.6% and specificity of 84.1% (in the case of maximum amplitude of total current vector). Furthermore, the subtraction MCG magnitude and its current distribution can reflect the expanse of the ischemic lesion area and the progress from ischemia to myocardial infarction.

Ann Noninvasive Electrocardiol 2010;15(4):360‐368
The Year of 2009 in Electrocardiology
Authors: Stern Shlomo
Published: October 2010

Ann Noninvasive Electrocardiol 2010;15(4):378‐383
“Awakenings”: Electrocardiographic Findings in Central Sleep Apnea
Authors: Littmann Laszlo , Nesbit Ross M. , Blackwell J. Matthew
Published: October 2010

Central sleep apnea is an important but frequently missed clinical diagnosis. The purpose of this clinical case series is to demonstrate that in a subset of patients with central sleep apnea, inpatient telemetry ECG recordings may reveal a consistent relationship between changes in sinus rate, AV conduction, and the presence and rate of respiratory artifact that should raise the clinical suspicion of central sleep apnea. In the three presented cases, marked sinus bradycardia or AV block was followed by the simultaneous occurrence of abrupt acceleration of heart rate and the appearance of rapid micro‐oscillations consistent with respiratory artifact. These changes suggested central sleep apnea characterized by bradycardia during the apneic spells followed by awakening of the breathing center and postvagal tachycardia. In each case, central sleep apnea was confirmed by visual observation of the patient, documentation of arterial desaturations during episodes of bradycardia, and in two, by a subsequent sleep study. Physicians should be aware of the potential and significance of these electrocardiographic disturbances in patients with central sleep apnea.

Ann Noninvasive Electrocardiol 2010;15(4):387‐391
Grandmothers Raising Grandchildren: Results of an Intervention to Improve Health Outcomes
Authors: Kelley Susan J. , Whitley Deborah M. , Campos Peter E.
Published: October 2010

Purpose: To examine the impact of an intervention to improve the health of grandmothers raising grandchildren in parent‐absent homes.

Design: A longitudinal, pretest‐posttest design.

Methods: The sample was composed of 529 female caregivers with a mean age of 56.7 years (range 38–83) who were predominantly low‐income African Americans. Data were collected prior to the intervention and again at 12 months when the intervention was complete. The intervention involved home visitation by registered nurses and social workers, as well as other support services. The Short Form‐36 was used to assess physical and mental health, using eight multi‐item scales.

Results: A comparison of pre‐ and posttest mean scores on the SF‐36 indicated significantly (p < .003) improved mean scores for vitality, physical effects on role functioning, emotional effects on role functioning, and mental health. No significant differences were found for other attributes.

Conclusions: These preliminary findings suggest that grandmothers raising grandchildren may benefit from a home‐based intervention designed to improve health attributes. Implications for nursing practice, policy, and research are presented.

Clinical Relevance: The health of grandmother caregivers is critical to their ability to parent grandchildren successfully. Nurses practicing in a variety of settings are in a unique position to identify and address the health challenges of grandmothers who are raising grandchildren.
Acute Arsenic Poisoning: Clinical, Toxicological, Histopathological, and Forensic Features
Authors: Tournel Gilles , Houssaye Cédric , Humbert Luc , Dhorne Christine , Gnemmi Viviane , Bécart‐Robert Anne , Nisse Patrick , Hédouin Valéry , Gosset Didier , Lhermitte Michel
Published: October 2010

Abstract:  This report describes a suicide case by acute arsenic intoxication via intravenous injection. A 30‐year‐old woman injected arsenic As (V) (sodium arseniate disodique: Disodium Hydrogena Arsenik RP) in a successful suicide attempt. Three hours following administration, the woman developed severe digestive symptoms. She was admitted to a hospital and transferred to the intensive care unit within 12 h of the massive administration of arsenic. Despite therapeutic efforts, over the next 2 h she developed multiorgan failure and died. A postmortem examination was performed. Pulmonary edema and congestion of liver were apparent. As (V) and As (III) were determined by high performance liquid chromatography and inductively coupled plasma mass spectrometry after mineralization of samples by concentrated nitric acid. Toxicological analysis revealed high concentrations of arsenic in biological fluids as well as in organs. Histopathological examination showed a typical indication of myocarditis. These findings were in agreement with acute arsenic poisoning. The symptoms developed by this young woman (intoxication by intravenous administration) were comparable to oral intoxication. The clinical signs, survival time, and administration type are discussed in light of the literature on acute and chronic arsenic poisoning.
Plank Fence Penetration into Automobiles—Implications for Prevention Initiatives*
Authors: Procter Levi , Bernard Andrew , Ginn Gary , Kearney Paul , Pienkowski David
Published: October 2010

Abstract:  The wooden plank fence presents a deadly but unrecognized hazard to motorists. We hypothesize that fence plank injury is prevalent and results in significant morbidity and mortality. Databases of the University of Kentucky’s Level I Trauma Center and the Fayette County Coroner were retrospectively analyzed over a 12‐year period (1995–2006). One hundred and twenty‐eight subjects were involved in vehicle contact with wooden plank fences. One hundred and twenty‐three subjects were evaluated at the Emergency Department of our trauma center; 35 (27%) had a patient–plank interaction (PPI). Men (30/35) were more frequently involved (86%), and average age was 32.8 years. Thirty‐two (91%) were drivers; 14/35 (40%) died from PPI‐related injuries. The most common cause of death was blunt head trauma in 13 of these 14 fatally injured subjects (93%). This study provides new data underscoring the frequency, lethality, and economic consequences of this injury mechanism. Further research is needed to quantify the national prevalence of this problem and develop injury‐mitigating strategies pertaining to roadway or fence design.
A New Method for Casting Three‐Dimensional Shoeprints and Tire Marks with Dental Stone
Authors: Cohen Amit , Wiesner Sarena , Grafit Arnon , Shor Yaron
Published: October 2010

Abstract:  Dental stone is used as the major material for recovering three‐dimensional shoeprints and tire tracks from crime scenes. The procedure for using dental stone sparsely changed over the years. There are two common methods for mixing dental stone: (i) a premeasured amount of dental stone is put in a zip‐lock bag to which water is added, and (ii) the water and dental stone are mixed in a bucket. We suggest a novel rapid and efficient method of mixing dental stone and water in a bottle. These methods were compared at equal conditions. The parameters measured were the number of air bubbles, the strength of the cast, the ease of use, and the sharpness and quality of the accidental characteristics present in the cast. The proposed bottle method has the advantages of both the bucket and the zip‐lock methods hence it combines strength, sharpness, high quality, and ease of use.
Case Series of Completed Suicides by Burning Over a 13‐Year Period*
Authors: Cimino Patrick J. , Williams Timothy L. , Fusaro Aldo , Harruff Richard
Published: October 2010

Abstract:  Suicide by burning is an extreme act that is uncommon in the United States and throughout the Western world. The characteristics of people who complete such acts are not well understood. To address this issue, we examined the death records of the King County Medical Examiner’s Office in Washington State over the 13 years from 1996 to 2009. Twenty‐five cases of suicide by burning were identified and used to characterize decedent demographics, circumstances of death, and motivating factors. Compared to other methods of suicide, burning demonstrated a significant overrepresentation of decedents who were women, 40–59 years of age, and Asian/Pacific Islander. They also tended to have previous psychiatric illness and/or substance abuse issues. Self‐burning predominantly occurred at the decedent’s residence with the intent of suicide given. There was no unifying theme in motivating factors. Together, these data represent the characteristics of people whose death is because of suicide by burning in King County, Washington.
Dental Age Assessment: The Applicability of Demirjian Method in Eastern Turkish Children
Authors: Celikoglu Mevlut , Cantekin Kenan , Ceylan Ismail
Published: October 2010

Abstract:  In the literature, little is known about the applicability of this method in Turkish children. The aim of this study was, therefore, to evaluate the reliability of Demirjian method of age estimation when used for eastern Turkish children. A retrospective study was performed on a sample of panoramic radiographs taken from 807 healthy eastern Turkish children. The stages of dental maturity of the mandibular left seven permanent teeth for each subject using the eight radiographic dental maturity stages demonstrated by Demirjian were evaluated. A paired t‐test was used for statistical analysis. The mean difference between the chronological and dental ages ranged from 0.2 to 1.9 years in girls and from 0.4 to 1.3 years in boys. The differences between the chronological and dental ages were statistically significant in all age groups. The applicability of Demirjian method is not suitable for eastern Turkish population.
The ‘Break Enter and Die’ Syndrome May Involve Significant Injury to Major Neck Vessels
Authors: Byard Roger W.
Published: October 2010

Abstract:  Death from incised wounds of major vessels may occur during illegal entry of premises. Wounds are often relatively unimpressive having been caused by thin shards of glass. Alcohol and/or drugs have often been taken that have impaired coordination and contributed to a failure to take appropriate action. A 37‐year‐old man slipped and fell while attempting to enter a house through a window that he had just broken. He was found dead surrounded by a large amount of blood. At autopsy, a single horizontal, deeply incised wound of the anterior neck was present with transection of the internal jugular veins bilaterally and the right common carotid artery. Toxicological studies were negative for alcohol and common drugs. Death was due to exsanguination and air embolism. This case demonstrates that the injuries sustained during such activities may be quite extensive and involve major neck vessels. Alcohol and drug intoxication are not necessarily involved.
Fragrance mix II in the baseline series contributes significantly to detection of fragrance allergy
Authors: Heisterberg Maria V , Andersen Klaus E , Avnstorp Christian , Kristensen Berit , Kristensen Ove , Kaaber Knud , Laurberg Grete , Menné Torkil , Nielsen Niels Henrik , Sommerlund Mette , Thormann Jens , Veien Niels K , Vissing Susanne , Johansen Jeanne D
Published: October 2010

Background: Fragrance mix II (FM II) is a relatively new screening marker for fragrance contact allergy. It was introduced in the patch test baseline series in Denmark in 2005 and contains six different fragrance chemicals commonly present in cosmetic products and which are known allergens.

Aim: To investigate the diagnostic contribution of including FM II in the baseline series by comparing it with other screening markers of fragrance allergy: fragrance mix I (FM I), Myroxylon pereirae and hydroxyisohexyl 3‐cyclohexene carboxaldehyde (HICC).

Method: Retrospective study of 12 302 patients consecutively patch tested with FM II by members of the Danish Contact Dermatitis Group 2005–2008.

Results: FM II gave a positive patch test in 553 patients (4.5%), and in 72.2% of these patients the reaction was judged to be clinically relevant. FM II ranked second in detecting fragrance allergy, after FM I. If FM II had not been included as a screening marker in the baseline series, 15.6% (n = 202) of individuals with fragrance allergy would not have been identified by the other fragrance screening markers (FM I, M. pereirae or HICC).

Conclusion: FM II contributes substantially to detecting fragrance allergy. It ranked second among the fragrance screening markers tested in the baseline series and detects individuals with an allergy who otherwise would not have been identified.
Patch testing with fragrance mix II: results of the IVDK 2005–2008
Authors: Krautheim Andrea , Uter Wolfgang , Frosch Peter , Schnuch Axel , Geier Johannes
Published: October 2010

Background: The fragrance mix (FM I), established in 1977, detects the majority, but not all cases of contact allergy to fragrances. Based on European research 2002/2003, fragrance mix II (FM II) was developed to supplement FM I. In 2005, the German Contact Dermatitis Research Group (DKG) added FM II to their baseline series.

Objectives: To evaluate reactions to FM II and its constituents in routine patch testing.

Methods: Retrospective data analysis of the Information Network of Departments of Dermatology (IVDK), 2005–2008, of patch test results with FM II and its constituents.

Results: A total of 35 633 patients were patch tested with FM II as part of the DKG baseline series. Of these, 1742 (4.9%) reacted positively. Concomitant reactions to FM I were observed in 41.9% of the patients reacting to FM II. In 367 FM II‐positive patients, a full breakdown test of the mix was performed. Of these, 47.7% reacted to hydroxyisohexyl 3‐cyclohexene carboxaldehyde, 16.1% to citral, 11.4% to farnesol, 3.8% to hexyl cinnamal, 2.7% to coumarin, and 2.5% to citronellol.

Conclusions: FM II is an important screening and diagnostic tool to detect fragrance allergy. Hydroxyisohexyl 3‐cyclohexene carboxaldehyde is the most important fragrance allergen in FM II.
Fragrance mix I patch test reactions in 5006 consecutive dermatitis patients tested simultaneously with TRUE Test® and Trolab® test material
Authors: Mortz Charlotte Gotthard , Andersen Klaus Ejner
Published: October 2010

Background: The prevalence of contact allergy to fragrance mix (FM) I varies from study to study, depending on factors such as test population, patch test material, and technique.

Objectives: To compare the outcome of routine patch testing with FM I TRUE Test and FM I Trolab.

Materials and Methods: A total of 5006 consecutive eczema patients were patch tested with both patch test materials according to the International Contact Dermatitis Research Group.

Results: A total of 9.9% patients tested had a positive reaction to one of the FM I mixes; 4.4% to FM I TRUE Test, 9.3% to FM I Trolab, and 3.7% to both (P < 0.0001). Patients with a stronger reaction to FM I TRUE Test almost all reacted to FM I Trolab, whereas the reverse situation showed a lower association. Clinical relevance of a positive patch test reaction to FM I TRUE Test was found in 73.0%, and clinical relevance of a positive patch test reaction to FM I Trolab was found in 64.3%; 68.4% of the patients with a positive reaction to FM I TRUE Test and 54.3% with a positive reaction to FM I Trolab were positive to one or more of the eight constituents of the mix.

Limitations: The study is retrospective, and supplementary testing with FM components in patients with a positive reaction to the mixes was performed in a selected group of patients. Determination of clinical relevance may be biased.

Conclusions: From this study, we cannot conclude which of the two FM I test preparations is the best for diagnostic purposes. Inclusion of both FM I tests in the baseline series to obtain a graded degree of FM I allergy for the individual patient is one option. Prospective controlled patch test studies with FM I patch test material are recommended.
Long‐term prophylaxis of hereditary angioedema with androgen derivates: a critical appraisal and potential alternatives
Authors: Maurer Marcus , Magerl Markus
Published: October 2010

Androgen derivatives are regarded as standard in the long‐term prophylaxis of swelling attacks in patients with hereditary angioedema (HAE). Because of their relatively slow onset of action, they are not suitable for acute therapy. Long‐term prophylaxis with androgen derivatives must be regarded critically, especially on account of their androgenic and anabolic effects, some of which are severe. The risk of adverse events increases with the daily dose and the duration of treatment. Thus, treatment always calls for close monitoring of patients with regard to potential adverse events. In addition, androgens are subject to numerous contraindications and they show interactions with a large number of other drugs. Off‐label use, doping issues, clarification of reimbursement and the need to import the androgen derivatives, which are no longer marketed in Germany, result in additional effort for the treating physician in terms of logistics and time involved.

In symptomatic treatment of acute attacks the intravenous substitution of C1‐INH and – since 2008 – subcutaneous administration of icatibant are available. The two substances are well tolerated and their effect occurs rapidly and, when the diagnosis has been confirmed, reliably. In the light of these two treatment options for controlling acute attacks, prophylactic treatment of HAE patients with androgen derivatives such as danazol should be reassessed. Patients might benefit from a dose reduction or the withdrawal of androgen prophylaxis and attacks can be controlled with demand‐oriented acute treatment using C1‐INH or icatibant.
WFIKKN1 and WFIKKN2 bind growth factors TGFβ1, BMP2 and BMP4 but do not inhibit their signalling activity
Authors: Szláma György , Kondás Katalin , Trexler Mária , Patthy László
Published: October 2010

WFIKKN1 and WFIKKN2 are large extracellular multidomain proteins consisting of a WAP domain, a follistatin domain, an immunoglobulin domain, two Kunitz‐type protease inhibitor domains and an NTR domain. Recent experiments have shown that both proteins have high affinity for growth and differentiation factor (GDF)8 and GDF11. Here we study the interaction of WFIKKN proteins with several additional representatives of the transforming growth factor (TGF)β family using SPR measurements. Analyses of SPR sensorgrams suggested that, in addition to GDF8 and GDF11, both WFIKKN proteins bind TGFβ1, bone morphogenetic protein (BMP)2 and BMP4 with relatively high affinity (Kd ∼ 10−6 m). To assess the biological significance of these interactions we studied the effect of WFIKKN proteins on the activity of GDF8, GDF11, TGFβ1, BMP2 and BMP4 using reporter assays. These studies revealed that WFIKKN1 and WFIKKN2 inhibited the biological activity of GDF8 and GDF11 in the nanomolar range, whereas they did not inhibit the activities of TGFβ1, BMP2 and BMP4 even in the micromolar range. Our data indicate that WFIKKN proteins are antagonists of GDF8 and GDF11, but in the case of TGFβ1, BMP2 and BMP4 they function as growth factor binding proteins. It is suggested that the physical association of WFIKKN proteins with these growth factors may localize their action and thus help to establish growth factor gradients in the extracellular space.

Structured digital abstract

 A list of the large number of protein‐protein interactions described in this article is available via the MINT article MINT‐8044119
The antagonistic effect of hydroxyl radical on the development of a hypersensitive response in tobacco
Authors: Deng Sheng , Yu Mina , Wang Ying , Jia Qin , Lin Ling , Dong Hansong
Published: October 2010

Reactive oxygen species (ROS) are important signalling molecules in living cells. It is believed that ROS molecules are the main triggers of the hypersensitive response (HR) in plants. In the present study of the effect of riboflavin, which is excited to generate ROS in light, on the development of the HR induced by the elicitin protein ParA1 in tobacco (Nicotiana tabacum), we found that the extent of the ParA1‐induced HR was diminished by hydroxyl radical (OH•), a type of ROS. As compared with the zones treated with ParA1 only, the HR symptom in the zones that were infiltrated with ParA1 plus riboflavin was significantly diminished when the treated plants were placed in the light. However, this did not occur when the plants were maintained in the dark. Trypan blue staining and the ion leakage measurements confirmed HR suppression in the light. Further experiments proved that HR suppression is attributed to the involvement of the photoexcited riboflavin, and that the suppression can be eliminated with the addition of hydrogen peroxide scavengers or OH• scavengers. Fenton reagent treatment and EPR measurements demonstrated that it is OH• rather than hydrogen peroxide that contributes to HR suppression. Accompanying the endogenous OH• formation, suppression of the ParA1‐induced HR occurred in the tobacco leaves that had been treated with high‐level abscisic acid, and that suppression was also removed by OH• scavengers. These results offer evidence that OH•, an understudied and little appreciated ROS, participates in and modulates biologically relevant signalling in plant cells.
Society not State: The challenge of the Big Society
Authors: Glasman Maurice
Published: October 2010

In ‘Big Society’, David Cameron launched the most successful neologism of the 2010 general election campaign. But, as Maurice Glasman argues, the Big Society introduces – or reintroduces – some substantial ideas about democracy and devolution, and has started a political conversation that the left needs to join.
Dreams of a social economy
Authors: Mayo Ed
Published: October 2010

Ed Mayo looks at the work and ideas of John Bird, Iain Tuckett and Edgar Cahn and gleans some salient lessons for the construction of the social economy in its latest guise.
Localism the American way
Authors: Grayson Richard S
Published: October 2010

Richard S Grayson suggests that in making democratic localism work, the UK could look more at the United States' radically decentralised system. Using the example of Newark's pioneering mayor Cory Booker, he argues that strong elected mayors can bring about significant change, even in difficult circumstances.
No‐brain tax
Authors: Johnson Michael
Published: October 2010

By now, Lord Browne's review of higher education ought to have published its recommendations. Looking back at Vince Cable's proposals for a graduate tax, Michael Johnson considers the possible effects – on students, universities and the public purse – of changing the funding model for our hallowed halls of learning.
Restraints or alternatives: safety work in care of older persons
Authors: Ludwick Ruth , O’Toole Richard , Meehan Anita
Published: October 2010

ludwick r., o’toole r. & meehan a. (2012) Restraints or alternatives: safety work in care of older persons.International Journal of Older People Nursing7, 11–19   doi: 10.1111/j.1748‐3743.2010.00244.x

Aim. To examine the factors and complexity that account for physical restraints use and their alternatives as nurses’ protect the safety of older adults.

Background. Research on physical restraints has repeatedly shown the human, financial and work costs associated with their use, but their use continues to be a major quality issue across hospitals and across countries for older persons.

Method. Interviews with medical surgical nurses in a Midwestern hospital in the United States were recorded and interpreted using grounded theory.

Results. Using data that described the complexity of initiating, maintaining, or discontinuing restraints, we captured the density of these processes and showed how nurses made decisions about restraint use. The tasks carried out to protect the older person’s safety often involved using restraints or their alternatives and these tasks then set in motion a cascade of other types of tasks or work, e.g. diagnostic, comfort, articulation.

Conclusions. The study extended the work on chronic illness trajectories and formulated a framework for understanding the complexity of the use of restraints and their alternatives. Using a tracing approach we were able to predict the types of situations that would most likely result in the initiation, maintenance and discontinuation of restraints or the use of alternative procedures.

Relevance to practice. The study has identified a process of ‘safety work’ that identified the risk associated with the problem, the work to cope with the problem and risk, the conditions that influenced the process and the consequences or outcomes of the work strategies to maintain the older person’s safety.
Characterization of the ‘pristinamycin supercluster’ of Streptomyces pristinaespiralis
Authors: Mast Yvonne , Weber Tilmann , Gölz Melanie , Ort‐Winklbauer Regina , Gondran Anne , Wohlleben Wolfgang , Schinko Eva
Published: October 2010

Pristinamycin, produced by Streptomyces pristinaespiralis Pr11, is a streptogramin antibiotic consisting of two chemically unrelated compounds, pristinamycin I and pristinamycin II. The semi‐synthetic derivatives of these compounds are used in human medicine as therapeutic agents against methicillin‐resistant Staphylococcus aureus strains. Only the partial sequence of the pristinamycin biosynthetic gene cluster has been previously reported. To complete the sequence, overlapping cosmids were isolated from a S. pristinaespiralis Pr11 gene library and sequenced. The boundaries of the cluster were deduced, limiting the cluster size to approximately 210 kb. In the central region of the cluster, previously unknown pristinamycin biosynthetic genes were identified. Combining the current and previously identified sequence information, we propose that all essential pristinamycin biosynthetic genes are included in the 210 kb region. A pristinamycin biosynthetic pathway was established. Furthermore, the pristinamycin gene cluster was found to be interspersed by a cryptic secondary metabolite cluster, which probably codes for a glycosylated aromatic polyketide. Gene inactivation experiments revealed that this cluster has no influence on pristinamycin production. Overall, this work provides new insights into pristinamycin biosynthesis and the unique genetic organization of the pristinamycin gene region, which is the largest antibiotic ‘supercluster’ known so far.
Electroacupuncture Protected Pyramidal Cells in Hippocampal CA1 Region of Vascular Dementia Rats by Inhibiting the Expression of P53 and Noxa
Authors: Zhu Yanzhen , Zeng Yanjun
Published: October 2010

Aim: Clinically electroacupuncture (EA) is proved an effective therapy for vascular dementia (VD), but their mechanisms remain uncertain. The aim of this study was to determine whether EA protects pyramidal cells from apoptosis in hippocampus of a VD rat model by inhibiting the expression of p53 and Noxa. Methods: One month after a VD animal model was established by bilateral occlusion of common carotid arteries, EA treatment was given at “Baihui” (DU20), “Dazhui” (DU14), and “Shenshu” (BL23). The learning and memory ability was assessed by Morris water maze. Neuronal apoptosis in hippocampus was evaluated with hematoxylin–eosin (HE) staining, and the expression of p53 and Noxa was analyzed by confocal laser scanning microscope with immunofluorescence staining. Results: Expressions of p53 and Noxa in the EA group and sham‐operated group were less than in the VD model group (P < 0.01), and the expression of p53 was positively correlated to expression of Noxa in hippocampus of VD rats (r = 0.918, P < 0.01). EA treatment could reduce the amount of apoptotic neurons in hippocampal CA1 area of rats with VD. The average latency in the Morris water maze test was significantly shorter, and escape strategies improved from edge and random searches to more linear swim pathway in the EA group compared with the VD model group (P < 0.01). Conclusions: The increasing expressions of p53 and Noxa play important roles in the pathogenesis of VD. EA improves learning and memory ability and protects pyramidal cells from apoptosis by blocking expression of p53 and Noxa in the hippocampal CA1 region of VD rats. These results suggest a novel mechanism of EA treatment to VD.
Melatonin Receptor Agonists: New Options for Insomnia and Depression Treatment
Authors: Spadoni Gilberto , Bedini Annalida , Rivara Silvia , Mor Marco
Published: October 2010

The circadian nature of melatonin (MLT) secretion, coupled with the localization of MLT receptors to the suprachiasmatic nucleus, has led to numerous studies of the role of MLT in modulation of the sleep‐wake cycle and circadian rhythms in humans. Although much more needs to be understood about the various functions exerted by MLT and its mechanisms of action, three therapeutic agents (ramelteon, prolonged‐release MLT, and agomelatine) are already in use, and MLT receptor agonists are now appearing as new promising treatment options for sleep and circadian‐rhythm related disorders. In this review, emphasis has been placed on medicinal chemistry strategies leading to MLT receptor agonists, and on the evidence supporting therapeutic efficacy of compounds undergoing clinical evaluation. A wide range of clinical trials demonstrated that ramelteon, prolonged‐release MLT and tasimelteon have sleep‐promoting effects, providing an important treatment option for insomnia and transient insomnia, even if the improvements of sleep maintenance appear moderate. Well‐documented effects of agomelatine suggest that this MLT agonist offers an attractive alternative for the treatment of depression, combining efficacy with a favorable side effect profile. Despite a large number of high affinity nonselective MLT receptor agonists, only limited data on MT1or MT2subtype‐selective compounds are available up to now. Administration of the MT2‐selective agonistIIK7to rats has proved to decrease NREM sleep onset latency, suggesting that MT2receptor subtype is involved in the acute sleep‐promoting action of MLT; rigorous clinical studies are needed to demonstrate this hypothesis. Further clinical candidates based on selective activation of MT1or MT2receptors are expected in coming years.
Lacosamide and Epilepsy
Authors: Harris Jacklyn A. , Murphy Julie A.
Published: October 2010

We will review all available studies on the use of lacosamide in the treatment of partial‐onset seizures. The available evidence includes two open‐label studies and three randomized controlled trials evaluating the safety and efficacy of oral lacosamide. One open‐label study and one randomized controlled trial evaluating the safety and tolerability of intravenous lacosamide was also identified. Lacosamide was found to be efficacious with significant reduction in seizure frequency dosed 400–600 mg daily. Moreover, its adverse drug effects were mild and infrequently reported in the literature. Findings suggest that lacosamide is an effective agent for adjunctive treatment of refractory partial‐onset seizures.
Role of Spinal Neurotransmitter Receptors in Itch: New Insights into Therapies and Drug Development
Authors: Cevikbas Ferda , Steinhoff Martin , Ikoma Akihiko
Published: October 2010

Targets for antipruritic therapies are now expanding from the skin to the central nervous system. Recent studies demonstrate that various neuronal receptors in the spinal cord are involved in pruritus. The spinal opioid receptor is one of the best‐known examples. Spinal administration of morphine is frequently accompanied by segmental pruritus. In addition to μ‐opioid receptor antagonists, κ‐opioid receptor agonists have recently come into usage as novel antipruritic drugs, and are expected to suppress certain subtypes of itch such as hemodialysis‐ and cholestasis‐associated itch that are difficult to treat with antihistamines. The gastrin‐releasing peptide receptor in the superficial dorsal horn of the spinal cord has also received recent attention as a novel pathway of itch‐selective neural transmission. The NMDA glutamate receptor appears to be another potential target for the treatment of itch, especially in terms of central sensitization. The development of NMDA receptor antagonists with less undesirable side effects on the central nervous system might be beneficial for antipruritic therapies. Drugs suppressing presynaptic glutamate‐release such as gabapentin and pregabalin also reportedly inhibit certain subtypes of itch such as brachioradial pruritus. Spinal receptors of other neuromediators such as bradykinin, substance P, serotonin, and histamine may also be potential targets for antipruritic therapies, given that most of these molecules interfere not only with pain, but also with itch transmission or regulation. Thus, the identification of itch‐specific receptors and understanding itch‐related circuits in the spinal cord may be innovative strategies for the development of novel antipruritic drugs.