bluuebunny/crossref_metadata_2025 huggingface dataset:
A survey of seizures and current treatments in 15q duplication syndrome
Authors: Conant Kerry D. , Finucane Brenda , Cleary Nicole , Martin Ashley , Muss Candace , Delany Mary , Murphy Erin K. , Rabe Olivia , Luchsinger Kadi , Spence Sarah J. , Schanen Carolyn , Devinsky Orrin , Cook Edwin H. , LaSalle Janine , Reiter Lawrence T. , Thibert Ronald L.
Published: February 2014

Objective

Seizures are common in individuals with duplications of chromosome 15q11.2‐q13 (Dup15q). The goal of this study was to examine the phenotypes and treatments of seizures in Dup15q in a large population.

Methods

A detailed electronic survey was conducted through the Dup15q Alliance containing comprehensive questions regarding seizures and their treatments in Dup15q.

Results

There were 95 responses from Dup15q families. For the 83 with idic(15), 63% were reported to have seizures, of which 81% had multiple seizure types and 42% had infantile spasms. Other common seizure types were tonic–clonic, atonic, myoclonic, and focal. Only 3 of 12 individuals with int dup(15) had seizures. Broad spectrum antiepileptic drugs (AEDs) were the most effective medications, but carbamazepine and oxcarbazepine were also effective, although typical benzodiazepines were relatively ineffective. There was a 24% response rate (>90% seizure reduction) to the first AED tried. For those with infantile spasms, adrenocorticotropic hormone (ACTH) was more effective than vigabatrin.

Significance

This is the largest study assessing seizures in Duplication 15q syndrome, but because this was a questionnaire‐based study with a low return rate, it is susceptible to bias. Seizures are common in idic(15) and typically difficult to control, often presenting with infantile spasms and progressing to a Lennox‐Gastaut–type syndrome. Seizures in those with int dup(15) are less common, with a frequency similar to the general autism population. In addition to broad spectrum AED, medications such as carbamazepine and oxcarbazepine are also relatively effective in controlling seizures in this population, suggesting a possible multifocal etiology, which may also explain the high rate of infantile spasms. Our small sample suggests a relative lack of efficacy of vigabatrin and other γ‐aminobutyric acid (GABA)ergic medications, such as typical benzodiazepines, which may be attributable to abnormal GABAergic transmission resulting from the duplication of a cluster of GABAβ3 receptor genes in the 15q11.2‐13 region.
Patterns of diagnosis and therapeutic care of epilepsy at a tertiary referral center in Nigeria
Authors: Igwe Stanley C. , Brigo Francesco , Beida Omeiza
Published: February 2014

Objective

Epilepsy care in developing countries is challenged by the paucity of trained specialists, diagnostic tools, and antiepileptic drugs (AEDs). We retrospectively evaluated how epilepsy was managed in a Nigerian tertiary referral center, with the goals of determining diagnostic accuracy by comparing clinical and electroencephalography (EEG) diagnoses, the appropriateness of prescribed therapy by clinician specialization, and the association between therapy and patient outcomes.

Methods

We examined the medical records of 372 patients diagnosed with epilepsy in the center over a 6‐month period from 2011 to 2012. Data were obtained on methods of diagnosis, clinician specialization, therapeutic care, and patient self‐ or caregiver‐reported outcome on follow‐up visits. Interrater agreement was assessed using Cohen's κ coefficient, and the diagnoses made by nonspecialist and specialist clinicians compared using the chi‐square test.

Results

Of 372 patients diagnosed with epilepsy, only one had a brain computerized tomography (CT) scan. Seventy‐six were differentially diagnosed for generalized or partial epilepsy by both clinical presentation and EEG. Low interrater agreement (κ = 0.05) was found between these methods of diagnosis. Of the 76 patients, 53 (69.7%) received therapies judged as appropriate, with no significant difference in prescription rates for appropriate therapy between nonspecialists and specialists (p = 0.536). Specific syndromic diagnoses were made only in 4% of patients, and only in patients who underwent EEG. Only three first‐generation AEDs were prescribed, with 97.6% of patients receiving carbamazepine.

Significance

The discrepancy between diagnoses made on clinical features alone versus EEG diagnosis suggests that in many patients without concomitant EEG, the epileptic syndrome might have been erroneously classified, with increased risk of inappropriate treatment. Resources should be more properly directed toward increasing access to diagnostic facilities and newer generation AEDs.
Is focal cortical dysplasia sporadic? Family evidence for genetic susceptibility
Authors: Leventer Richard J. , Jansen Floor E. , Mandelstam Simone A. , Ho Alice , Mohamed Ismail , Sarnat Harvey B. , Kato Mitsuhiro , Fukasawa Tatsuya , Saitsu Hirotomo , Matsumoto Naomichi , Itoh Masayuki , Kalnins Renate M. , Chow Chung W. , Harvey A. Simon , Jackson Graeme D. , Crino Peter B. , Berkovic Samuel F. , Scheffer Ingrid E.
Published: February 2014

Focal cortical dysplasia is a common cortical malformation and an important cause of epilepsy. There is evidence for shared molecular mechanisms underlying cortical dysplasia, ganglioglioma, hemimegalencephaly, and dysembryoplastic neuroepithelial tumor. However, there are no familial reports of typical cortical dysplasia or co‐occurrence of cortical dysplasia and related lesions within the same pedigree. We report the clinical, imaging, and histologic features of six pedigrees with familial cortical dysplasia and related lesions. Twelve patients from six pedigrees were ascertained from pediatric and adult epilepsy centers, eleven of whom underwent epilepsy surgery. Pedigree data, clinical information, neuroimaging findings, and histopathologic features are presented. The families comprise brothers with focal cortical dysplasia, a male and his sister with focal cortical dysplasia, a female with focal cortical dysplasia and her brother with hemimegalencephaly, a female with focal cortical dysplasia and her female first cousin with ganglioglioma, a female with focal cortical dysplasia and her male cousin with dysembryoplastic neuroepithelial tumor, and a female and her nephew with focal cortical dysplasia. This series shows that focal cortical dysplasia can be familial and provides clinical evidence suggesting that cortical dysplasia, hemimegalencephaly, ganglioglioma, and dysembryoplastic neuroepithelial tumors may share common genetic determinants.

A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.
Circadian rhythms on skin function of hairless rats: light and thermic influences
Authors: Flo Ana , Díez‐Noguera Antoni , Calpena Ana C. , Cambras Trinitat
Published: February 2014

Circadian rhythms are present in most functions of living beings. We have demonstrated the presence of circadian rhythms in skin variables (transepidermal water loss, TEWL; stratum corneum hydration, SCH; and skin temperature) in hairless rats under different environmental conditions of light and temperature. Circadian rhythms in TEWL and SCH showed mean amplitudes of about 20% and 14% around the mean, respectively, and appeared under light–dark cycles as well as under constant darkness. Environmental temperature was able to override TEWL, but not SCH rhythm, evidencing the dependency of TEWL on the temperature. Mean daily values of TEWL and SCH, and also the amplitude of TEWL rhythm, increased with the age of the animal. Under constant light, situation that induces arrhythmicity in rats, SCH and TEWL were inversely correlated. The results suggest the importance to take into account the functional skin rhythms in research in dermatological sciences.
Epidermal expression of Lgr6 is dependent on nerve endings and Schwann cells
Authors: Liao Xin‐Hua , Nguyen Hoang
Published: February 2014

Lgr5/6 proteins are stem cell markers in various tissues. However, what determines their restricted expression pattern in these tissues remains unknown. We found that in skin, Lgr6 is not only expressed in the central isthmus, directly above the hair follicle bulge cells as reported previously, but also in the interfollicular epidermis. Lgr6 expression in skin is highly correlated with the innervation sites of cutaneous nerves. In the hair follicle, Lgr6 closely localizes with the surrounding nerve endings and their corresponding Schwann cells throughout the entire hair cycle. Furthermore, ablation of cutaneous nerves leads to degeneration of Schwann cells and diminished expression of Lgr6. Our results demonstrate that the nerve endings/Schwann cells control Lgr6 expression in skin, implying that they play a role in regulation of skin epithelial cells.
Simulation of Water‐Table Aquifers Using Specified Saturated Thickness
Authors: Sheets Rodney A. , Hill Mary C. , Haitjema Henk M. , Provost Alden M. , Masterson John P.
Published: February 2014

Simulating groundwater flow in a water‐table (unconfined) aquifer can be difficult because the saturated thickness available for flow depends on model‐calculated hydraulic heads. It is often possible to realize substantial time savings and still obtain accurate head and flow solutions by specifying an approximate saturated thickness a priori, thus linearizing this aspect of the model. This specified‐thickness approximation often relies on the use of the “confined” option in numerical models, which has led to confusion and criticism of the method. This article reviews the theoretical basis for the specified‐thickness approximation, derives an error analysis for relatively ideal problems, and illustrates the utility of the approximation with a complex test problem. In the transient version of our complex test problem, the specified‐thickness approximation produced maximum errors in computed drawdown of about 4% of initial aquifer saturated thickness even when maximum drawdowns were nearly 20% of initial saturated thickness. In the final steady‐state version, the approximation produced maximum errors in computed drawdown of about 20% of initial aquifer saturated thickness (mean errors of about 5%) when maximum drawdowns were about 35% of initial saturated thickness. In early phases of model development, such as during initial model calibration efforts, the specified‐thickness approximation can be a very effective tool to facilitate convergence. The reduced execution time and increased stability obtained through the approximation can be especially useful when many model runs are required, such as during inverse model calibration, sensitivity and uncertainty analyses, multimodel analysis, and development of optimal resource management scenarios.
An evaluation of the bihyperbolic function in the optimization of the backpropagation algorithm
Authors: Miguez Geraldo , Xavier Adilson Elias , Maculan Nelson
Published: February 2014

The backpropagation algorithm is one of the most used tools for training artificial neural networks. However, this tool may be very slow in some practical applications. Many techniques have been discussed to speed up the performance of this algorithm and allow its use in an even broader range of applications. Although the backpropagation algorithm has been used for decades, we present here a set of computational results that suggest that by replacing bihyperbolic functions the backpropagation algorithm performs better than the traditional sigmoid functions. To the best of our knowledge, this finding was never previously published in the open literature. The efficiency and discrimination capacity of the proposed methodology are shown through a set of computational experiments, and compared with the traditional problems of the literature.
Formulations for an inventory routing problem
Authors: Archetti Claudia , Bianchessi Nicola , Irnich Stefan , Speranza M. Grazia
Published: February 2014

In this paper, we present and compare formulations for the inventory routing problem (IRP) where the demand of customers has to be served, over a discrete time horizon, by capacitated vehicles starting and ending their routes at a depot. The objective of the IRP is the minimization of the sum of inventory and transportation costs. The formulations include known and new mathematical programming formulations. Valid inequalities are also presented. The formulations are tested on a large set of benchmark instances. One of the most significant conclusions is that the formulations that use vehicle‐indexed variables are superior to the more compact, aggregate formulations.
Plant damage and herbivore performance change with latitude for two old‐field plant species, but rarely as predicted
Authors: Kim Tania N.
Published: February 2014

A long standing hypothesis in biogeography is that latitudinal gradients in plant defenses (LGPD) should arise because selection for plant defenses is greater in the tropics compared to temperate areas. Previous studies have focused on plant traits thought to confer resistance, yet many traits may not actually confer resistance (putative resistance) or interact to influence herbivore performance. In this study, I used a multi‐trophic approach to examine relationships between latitude, herbivore pressure, and plant resistance (measured as the growth rates of herbivores) of two old‐field plant species (Solanum carolinense and Solidago altissima) using a field survey across a 12 degree gradient in the eastern US combined with laboratory bioassays measuring the performance of generalist and specialist herbivores. I used structural equation modeling to examine the direct and indirect pathways by which latitude influences herbivore pressure and plant resistance. A latitudinal gradient in plant damage was observed in the expected direction for S. caroliense (damage decreased with latitude), but the opposite relationship was observed for S. altissima. Damage to both plant species was mediated by herbivore abundances, which was in turn influenced by predator abundances. Resistance to herbivores also varied with latitude but the form of the relationship was dependent on herbivore and plant species. There were direct, non‐linear relationships between latitude and resistance (for Spodoptera exigua and Schistocerca americana feeding on S. altissima; S. exigua and Manduca sexta feeding on S. carolinense). Herbivore growth rates were also mediated by the density of S. carolinense for Leptinotarsa juncta and S. americana feeding on S. carolinense. There was no relationship between plant resistance and herbivore pressure and no indication of feedbacks. Results from this study indicate that latitudinal variation in plant resistance is complex, possibly constrained by resource availability and tradeoffs in plant defenses.
Grazing‐induced changes in plant–soil feedback alter plant biomass allocation
Authors: Veen G. F. (Ciska) , de Vries Saskia , Bakker Elisabeth S. , van der Putten Wim H. , Olff Han
Published: February 2014

Large vertebrate herbivores, as well as plant–soil feedback interactions are important drivers of plant performance, plant community composition and vegetation dynamics in terrestrial ecosystems. However, it is poorly understood whether and how large vertebrate herbivores and plant–soil feedback effects interact. Here, we study the response of grassland plant species to grazing‐induced legacy effects in the soil and we explore whether these plant responses can help us to understand long‐term vegetation dynamics in the field.

In a greenhouse experiment we tested the response of four grassland plant species, Agrostis capillaris, Festuca rubra, Holcus lanatus and Rumex acetosa, to field‐conditioned soils from grazed and ungrazed grassland. We relate these responses to long‐term vegetation data from a grassland exclosure experiment in the field.

In the greenhouse experiment, we found that total biomass production and biomass allocation to roots was higher in soils from grazed than from ungrazed plots. There were only few relationships between plant production in the greenhouse and the abundance of conspecifics in the field. Spatiotemporal patterns in plant community composition were more stable in grazed than ungrazed grassland plots, but were not related to plant–soil feedbacks effects and biomass allocation patterns.

We conclude that grazing‐induced soil legacy effects mainly influenced plant biomass allocation patterns, but could not explain altered vegetation dynamics in grazed grasslands. Consequently, the direct effects of grazing on plant community composition (e.g. through modifying light competition or differences in grazing tolerance) appear to overrule indirect effects through changes in plant–soil feedback.
New ICP‐MS Results for Trace Elements in Five Iron‐Formation Reference Materials
Authors: Sampaio Geraldo Magela Santos , Enzweiler Jacinta
Published: February 2014

Iron formations (IFs) typically contain low mass fractions of most trace elements, including the rare earth elements (REE), and few publications describe analytical methods dedicated to this matrix. In this study, we used bomb and table‐top acid dissolution procedures and ICP‐MS to determine the mass fractions of trace elements in IF reference materials FER‐1, FER‐2, FER‐3, FER‐4 and IF‐G. The full digestion of the IF samples with the bomb procedure required the addition of a small amount of water together with the acids. The results obtained by this method mostly agreed statistically with published values. The most remarkable exception was the higher values obtained for the heavy REE in FER‐3. The recoveries of the REE obtained with the table‐top procedure were slightly higher than those of the bomb digestion, except for the values of the heavy REE in FER‐3 and FER‐4, which were up to 30% lower than published values. Sintering of the samples with sodium peroxide was performed to determine the REE, but the results tended to be lower than those derived following acid digestion. On the whole, the recoveries showed dependence on the conditions of digestion, but subtle differences in trace mineral composition between samples also exerted influence on the analytical results for trace elements.
Environmental modulation of the onset of air breathing and survival of Betta splendens and Trichopodus trichopterus
Authors: Mendez‐Sanchez J. F. , Burggren W. W.
Published: February 2014

The effect of hypoxia on air‐breathing onset and survival was determined in larvae of the air‐breathing fishes, the three spot gourami Trichopodus trichopterus and the Siamese fighting fish Betta splendens. Larvae were exposed continuously or intermittently (12 h nightly) to an oxygen partial pressure (PO2) of 20, 17 and 14 kPa from 1 to 40 days post‐fertilization (dpf). Survival and onset of air breathing were measured daily. Continuous normoxic conditions produced a larval survival rate of 65–75% for B. splendens and 15–30% for T. trichopterus, but all larvae of both species died at 9 dpf in continuous hypoxia conditions. Larvae under intermittent (nocturnal) hypoxia showed a 15% elevated survival rate in both species. The same conditions altered the onset of air breathing, advancing onset by 4 days in B. splendens and delaying onset by 9 days in T. trichopterus. These interspecific differences were attributed to air‐breathing characteristics: B. splendens was a non‐obligatory air breather after 36 dpf, whereas T. trichopterus was an obligatory air breather after 32 dpf.
Carbon Recycling for Renewable Materials and Energy Supply
Authors: Bringezu Stefan
Published: February 2014

The current flow of carbon for the production, use, and waste management of polymer‐based products is still mostly linear from the lithosphere to the atmosphere with rather low rates of material recycling. In view of a limited future supply of biomass, this article outlines the options to further develop carbon recycling (C‐REC). The focus is on carbon dioxide (CO2) capture and use for synthesis of platform chemicals to produce polymers. CO2 may be captured from exhaust gases after combustion or fermentation of waste in order to establish a C‐REC system within the technosphere. As a long‐term option, an external C‐REC system can be developed by capturing atmospheric CO2. A central role may be expected from renewable methane (or synthetic natural gas), which is increasingly being used for storage and transport of energy, but may also be used for renewable carbon supply for chemistry. The energy input for the C‐REC processes can come from wind and solar systems, in particular, power for the production of hydrogen, which is combined with CO2 to produce various hydrocarbons. Most of the technological components for the system already exist, and, first modules for renewable fuel and polymer production systems are underway in Germany. This article outlines how the system may further develop over the medium to long term, from a piggy‐back add‐on flow system toward a self‐carrying recycling system, which has the potential to provide the material and energy backbone of future societies. A critical bottleneck seems to be the capacity and costs of renewable energy supply, rather than the costs of carbon capture.
Average Hospital Length of Stay, Nurses’ Work Demands, and Their Health and Job Outcomes
Authors: Cho Sung‐Hyun , Park Mihyun , Jeon Sang Hee , Chang Hyoung Eun , Hong Hyun‐Ja
Published: February 2014

Purpose

To examine the relationship between average hospital length of stay (LOS) of nursing units and work demands perceived by nurses, and between work demands and nurses’ health and job outcomes.

Design

A cross‐sectional study using nurse survey data collected in a tertiary university hospital in Seoul, South Korea, in 2013 including 746 staff nurses working on 36 general, oncology, or intensive care units.

Methods

Each unit's average LOS was categorized as short (1st quartile), medium (2nd and 3rd quartiles), or long (4th quartile). Work demands (i.e., quantitative demands, work pace, and emotional demands), and nurses’ health and job outcomes were measured using the Copenhagen Psychosocial Questionnaire II. Their relationships were examined by multiple linear or logistic regression analyses with multilevel modeling.

Findings

The nurses reported high mean scores of work demands and poor health and job outcomes, compared with other occupations. The nurses working on units with a short or medium (vs. long) LOS perceived higher quantitative and emotional demands, and a higher work pace. Greater quantitative and emotional demands were associated with poor self‐rated health, greater sleeping troubles, work–family conflict, stress and burnout, lower job satisfaction, and a greater intent to leave. A higher work pace was also significantly related to greater work–family conflict.

Conclusions

A shorter LOS was associated with higher work demands, and higher work demands were associated with worse nurse outcomes. Thus, excessive work demands should be avoided to prevent nurses’ health and job outcomes from deteriorating.

Clinical Relevance

Nurse managers need to monitor the impacts of reducing LOS on work demands and nurse outcomes and request additional nurses to meet increasing work demands.
Geoepidemiology and space–time analysis of Primary biliary cirrhosis in Crete, Greece
Authors: Koulentaki M , Mantaka A , Sifaki‐Pistolla D , Thalassinos E , Tzanakis N , Kouroumalis E
Published: February 2014

Background & Aims

The prevalence of Primary biliary cirrhosis varies in different geographical areas. This might reflect genetic or environmental risk factors. We aimed to define Primary biliary cirrhosis prevalence and incidence, describe patient's spatial distribution, generate prediction maps and detect any possible routing pattern of time‐spatial appearance of the disease in Crete, Greece.

Methods

From 1990–2010, 245 Primary biliary cirrhosis patients diagnosed and followed up at the Gastroenterology Department of the University Hospital and the District Hospitals of the island, were contacted and 222 were included in the time–spatial analysis. To map their spatial distribution per 5‐year periods, geospatial models were applied in Gis–ArcMap 9.3 software. Kriging Interpolation methods were used to generate prediction maps for the disease in Crete. Areas of high and low probability of disease occurrence were estimated through multicriteria modelling. The disease route was defined by Gis‐ArcMap's toolbox.

Results

Prevalence was found to be 365 cases per million, with a mean incidence of 20.88 (range 3.79–35.99). Prediction map estimates from 1.22 to 11 patients per 50 km2 all over Crete. Areas of high risk of disease occurrence are located in the Eastern part, while low risk in the Western part of the island.

Discussion

Prevalence and incidence of Primary biliary cirrhosis in Crete are among the higher published in Europe. Given the homogeneous and stable study population and the geopolitics of the island, the heterogeneity in the time‐spatial distribution and the route of disease appearance strongly suggest a role for environmental causative agents.
Prevalence of renal abnormalities in chronic HBV infection: The HARPE study
Authors: Amet Sabine , Bronowicki Jean‐Pierre , Thabut Dominique , Zoulim Fabien , Bourliere Marc , Mathurin Philippe , de Ledinghen Victor , Benhamou Yves , Larrey Dominique G. , Janus Nicolas , Deray Gilbert , Launay‐Vacher Vincent , Pol Stanislas
Published: February 2014

Background & Aims

Few data are available on the prevalence of renal abnormalities in chronic hepatitis B virus (HBV)‐infected patients. The multicentric cross‐sectional HARPE study evaluated the prevalence of kidney disease indicators, in chronic HBV surface antigen carriers patients (HBsAg+) with active or inactive infection.

Patients and methods

Two hundred and sixty‐eight HBsAg+ adult patients, naïve of any oral antihepatitis B virus treatment were prospectively included over 2 years. Data for renal assessment were collected once from patient files. Univariate tests and multiple linear regressions were performed with the SAS software, version 8.02 (SAS, Inc., Cary, NC, USA).

Results

Among the 260 patients analysed, 58% were men, the mean age was 42 ± 14 years, 59.6% were inactive carriers whereas 47 patients, mostly active, were about to start an antiviral therapy. Prevalence of proteinuria, haematuria, glycosuria, uninfectious leukocyturia was 38.1%, 20.6%, 3.9% and 9% respectively. According to the international definition, a total of 64.6% of patients were found to have kidney disease. Diabetes, hypertension and dyslipidaemia were observed, respectively, in 4.6%, 9.2% and 38.8% patients. There were no significant differences in these results within the three subgroups.

Conclusion

Renal abnormalities are highly prevalent in our population and pre‐exist before the initiation of any antihepatitis B virus treatment. This emphasizes the need for: (i) a baseline renal evaluation in all HBs antigen‐positive patients; (ii) a regular renal monitoring before and during antihepatitis B virus treatment to diagnose and manage renal impairment and adjust antihepatitis B virus treatment doses to renal function when necessary.
Demographic processes shaping genetic variation of the solitarious phase of the desert locust
Authors: Chapuis Marie‐Pierre , Plantamp Christophe , Blondin Laurence , Pagès Christine , Vassal Jean‐Michel , Lecoq Michel
Published: February 2014

Between plagues, the solitarious desert locust (Schistocerca gregaria) is generally thought to exist as small populations, which are particularly prone to extinction events in arid regions of Africa and Asia. Given the high genetic structuring observed in one geographical area (the Eritrean coast) by former authors, a metapopulation dynamics model involving repeated extinction and colonization events was favoured. In this study, we assessed the validity of a demographic scenario involving temporary populations of the solitarious phase of the desert locust by analysing large‐scale population genetic data. We scored 24 microsatellites in 23 solitarious population samples collected over most of the species range during remission. We found very little genetic structuring and little evidence of declining genetic diversity. A Bayesian clustering method distinguished four genetically differentiated units. Three groups were largely consistent with three population samples which had undergone recent bottleneck events. Nevertheless, the last genetically homogeneous unit included all individuals from the remaining 18 population samples and did not show evidence of demographic disequilibrium. An approximate Bayesian computation treatment indicated a large population size for this main genetic group, moderately reduced between plague and remission but still containing tens of thousands of individuals. Our results diverge from the hypothesis of a classical metapopulation dynamics model. They instead support the scenario in which large populations persist in the solitarious phase of the desert locust.
Zone of proximal development (ZPD) as an ability to play in psychotherapy: A theory‐building case study of very brief therapy
Authors: Zonzi Anna , Barkham Michael , Hardy Gillian E. , Llewelyn Susan P. , Stiles William B. , Leiman Mikael
Published: February 2014

Objectives

This theory‐building case study examined the zone of proximal development (ZPD) in psychotherapy within the assimilation model. Theoretically, the ZPD is the segment of the continuum of therapeutic development within which assimilation of problematic experiences can take place. Work within a problem's current ZPD may be manifested as a Winnicottian ability to play, that is, an ability to adopt a flexible reflexive stance to the presenting problem and be involved in joint examination of possible alternatives. Play may be recognized in the client's receptivity to and creative use of the therapist's formulations of the presenting problems.

Design and methods

A case was selected from a comparative clinical trial of two very brief psychotherapies for mild to moderate depression, the Two‐Plus‐One Project (Barkham, Shapiro, Hardy, & Rees, 1999, J. Consult. Clin. Psychol., 67, 201). Martha, a woman in her late forties, received two sessions of psychodynamic‐interpersonal therapy 1 week apart and a follow‐up (‘plus one') session approximately 3 months later. Dialogical sequence analysis was used to analyse the transcripts of the three sessions.

Results

The analysis revealed Martha's problematic action pattern, which remained unchanged throughout the three sessions. Her ability to use and elaborate the therapist's formulations depended on the referential object that the therapist addressed; in particular, she seemed unable to play with the therapist's formulations of her more problematic experiences.

Conclusions

The case helped elucidate how the ZPD is content dependent. Winnicott's conception of playing emphasizes the quality of client response as an indicator of this content sensitivity. Differing breadths of major problems' ZPD, manifested as differing abilities to play with therapists' formulations may explain why some clients improve in psychotherapy while some do not.

Practitioner points

Accessing very problematic content may be very difficult even though the client's ability to mentalize other material appears ordinary.

Mildly depressed clients who have developed powerful care‐taking coping strategies may not respond to very brief therapeutic interventions.

A client's minimal acknowledgements may mislead the therapist into supplementing the client's failing self‐reflection rather than addressing the issue that provokes this failure.
Efficacy of Low‐Dose Ultraviolet A‐1 Phototherapy for Parapsoriasis/Early‐Stage Mycosis Fungoides
Authors: Aydogan Kenan , Yazici Serkan , Balaban Adim Saduman , Tilki Gunay Isil , Budak Ferah , Saricaoglu Hayriye , Tunali Sukran , Bulbul Baskan Emel
Published: February 2014

Mycosis fungoides (MF) and parapsoriasis (PP) are major dermatologic conditions for which phototherapy continues to be a successful and valuable treatment option. UVA‐1 phototherapy is effective in the management of cutaneous T‐cell mediated diseases. The aim of the study was to evaluate the efficacy and safety of low‐dose UVA‐1 phototherapy for the management of PP/early‐stage MF. A total of 30 patients, diagnosed with MF (n:19) or PP (n:11) were enrolled to the study. All patients were managed with low‐dose UVA‐1 (20 or 30 J cm−2). Response was assessed clinically and immunohistochemically. UVA‐1 treatment led to clinical and histological complete remission (CR) in 11 of 19 MF patients (57.9%), partial remission (PR) in three of 19 (15.8%), after a mean cumulative dose of 1665 (range, 860–3120) J cm−2 and mean number of 73 exposure (range, 43–107) sessions. Five patients with PP (45.5%) showed CR, and PR was observed in six patients with PP (54.5%) after a mean cumulative dose of 1723 (range, 1060–3030) J cm−2 and mean number of 74 exposure (range, 53–101) sessions. We conclude that low‐dose UVA‐1 therapy seems to be an effective, safe, and well‐tolerated treatment option for patients with PP/early‐stage MF.
Evidence for Unapparent Brucella canis Infections among Adults with Occupational Exposure to Dogs
Authors: Krueger W. S. , Lucero N. E. , Brower A. , Heil G. L. , Gray G. C.
Published: February 2014

Human serological assays designed to detect brucellosis will miss infections caused by Brucella canis, and low levels of periodic bacteremia limit diagnosis by blood culture. Recent B. canis outbreaks in dogs and concomitant illnesses in caretakers suggest that unapparent human infections may be occurring. With more than a quarter of a million persons in occupations involving dogs, and nearly 80 million dog owners in the United States, this pathogen is an under‐recognized human health threat. To investigate occupational exposure to B. canis, we adapted a commercial canine serological assay and present the first controlled seroepidemiological study of human B. canis infections in recent years. 306 adults with occupational exposure to dogs and 101 non‐matched, non‐canine‐exposed subjects were enrolled. Antibodies were detected using the canine D‐Tec® CB rapid slide agglutination test (RSAT) kit with a secondary 2‐mercaptoethanol (ME)‐RSAT. Results were validated on a blinded subset of sera with an additional RSAT and indirect enzyme‐linked immunoassay at the National Administration of Laboratories and Health Institutes (ANLIS) in Argentina. Seroprevalence ranged from 10.8% (RSAT) to 3.6% (ME‐RSAT) among canine‐exposed subjects. Kennel employees were more likely to test RSAT seropositive compared with other canine exposures (OR = 2.7; 95% CI, 1.3–5.8); however, low seroprevalence limited meaningful occupational risk factor analyses. Two seropositive participants reported experiencing symptoms consistent with brucellosis and having exposure to B. canis‐infected dogs; however, temporality of symptom onset with reported exposure could not be determined. D‐Tec® CB results had substantial agreement with ANLIS assays (Cohen's kappa = 0.60–0.68). These data add to a growing body of literature suggesting that people occupationally exposed to dogs may be at risk of unapparent B. canis infection. It seems prudent to consider B. canis as an occupational public health concern and encourage the development of serological assays to detect human B. canis infections.
Seroprevalence of Hepatitis E Virus in Domestic Pigs and Wild Boars in Switzerland
Authors: Burri C. , Vial F. , Ryser‐Degiorgis M.‐P. , Schwermer H. , Darling K. , Reist M. , Wu N. , Beerli O. , Schöning J. , Cavassini M. , Waldvogel A.
Published: February 2014

Hepatitis E is considered an emerging human viral disease in industrialized countries. Studies from Switzerland report a human seroprevalence of hepatitis E virus (HEV) of 2.6–21%, a range lower than in adjacent European countries. The aim of this study was to determine whether HEV seroprevalence in domestic pigs and wild boars is also lower in Switzerland and whether it is increasing and thus indicating that this zoonotic viral infection is emerging. Serum samples collected from 2,001 pigs in 2006 and 2011 and from 303 wild boars from 2008 to 2012 were analysed by ELISA for the presence of HEV‐specific antibodies. Overall HEV seroprevalence was 58.1% in domestic pigs and 12.5% in wild boars. Prevalence in domestic pigs was significantly higher in 2006 than in 2011. In conclusion, HEV seroprevalence in domestic pigs and wild boars in Switzerland is comparable with the seroprevalence in other countries and not increasing. Therefore, prevalence of HEV in humans must be related to other factors than prevalence in pigs or wild boars.
PCP and Septins Compartmentalize Cortical Actomyosin to Direct Collective Cell Movement
Authors: Shindo Asako , Wallingford John B.
Published: February 2014

Sculpting Actomyosin

The sculpting of embryos during development involves coordinated movement of cells in large groups. How actomyosin is controlled during such collective cell movement remains poorly understood. Working with developing
Xenopus
mesoderm,
Shindo and Wallingford
(p.
649
) found that planar cell polarity proteins and septins interface with the actomyosin machinery to control collective cell movement.
Classification of Interacting Electronic Topological Insulators in Three Dimensions
Authors: Wang Chong , Potter Andrew C. , Senthil T.
Published: February 2014

Interacting and Topological

Topological insulators (TIs), which have a bandgap and a robust conducting surface state protected by time-reversal symmetry, are typically materials with weak electron-electron interaction and are well-described by band theory. A major experimental goal has been to observe such symmetry-protected topological (SPT) phases in interacting systems.

Wang
et al.

(p.
629
) used a theoretical approach to classify SPT phases of interacting fermions in three dimensions and found six other phases in addition to the noninteracting ones. The results lay the groundwork for future microscopic models and inform the experimental search for such materials.
Loose Coupling Between Ca
2+
Channels and Release Sensors at a Plastic Hippocampal Synapse
Authors: Vyleta Nicholas P. , Jonas Peter
Published: February 2014

From Channel to Sensor

The coupling between voltage-activated calcium channels and calcium sensors of exocytosis on synaptic vesicles is a key factor that determines the timing and efficiency of transmitter release. It is still largely unclear how tight this coupling is at mature synapses in the central nervous system.
Vyleta and Jonas
(p.
665
) found that mossy fiber boutons contain high concentrations of endogenous calcium buffers that normally limit the amount of calcium that reaches the calcium sensor responsible for neurotransmitter release. As a consequence, the calcium signal available to trigger release is small for the initial action potential. However, after high-frequency stimulation, the endogenous calcium buffer binds calcium and is less able to buffer calcium entry, which allows more calcium to reach the calcium sensor, increasing neurotransmitter release and synaptic facilitation.
A Structurally Distinct Human Mycoplasma Protein that Generically Blocks Antigen-Antibody Union
Authors: Grover Rajesh K. , Zhu Xueyong , Nieusma Travis , Jones Teresa , Boero Isabel , MacLeod Amanda S. , Mark Adam , Niessen Sherry , Kim Helen J. , Kong Leopold , Assad-Garcia Nacyra , Kwon Keehwan , Chesi Marta , Smider Vaughn V. , Salomon Daniel R. , Jelinek Diane F. , Kyle Robert A. , Pyles Richard B. , Glass John I. , Ward Andrew B. , Wilson Ian A. , Lerner Richard A.
Published: February 2014

Easy M

Our immune systems can produce a vastly diverse repertoire of antibody molecules that each recognize and bind to a specific foreign antigen via a hypervariable region. However, there are a few bacterial antigens—such as Protein A, Protein G, and Protein L—that instead bind to the antibody's conserved regions and can bind to a large number of different antibodies. These high-affinity broad-spectrum antibody-binding properties have been widely exploited both in the laboratory and in industry for purifying, immobilizing, and detecting antibodies.

Grover
et al.

(p.
656
) have now identified Protein M found on the surface of human mycoplasma, which displays even broader antibody-binding specificity. The crystal structure of Protein M revealed how Protein-M binding blocks the antibody's antigen binding site. This mechanism may be exploited by mycoplasma to escape the humoral immune response.
Periodic Variability in the Large-Scale Southern Hemisphere Atmospheric Circulation
Authors: Thompson David W. J. , Barnes Elizabeth A.
Published: February 2014

Predictable Behavior

Few internally forced large-scale atmospheric circulation patterns exhibit periodic behavior, and those that do are centered in the tropics. Identifying these periodic processes is important for understanding the dynamics of weather.
Thompson and Barnes
(p.
641
) report the discovery of a 20- to 30-day periodicity in the atmospheric circulation in the Southern Hemisphere. The oscillation could potentially drive large-scale climate variability throughout much of the mid-latitude Southern Hemisphere.
Meeting Global Challenges
Authors: Sharp Phillip A. , Leshner Alan I.
Published: February 2014

Every major challenge of modern life, such as ensuring energy, health, water, or food security in a sustainable world with a predicted nine billion inhabitants, has complex science and technology (S&T) components and is global in character, even though its expression often involves national idiosyncrasies. Searching for solutions requires that the scientific community operate in fundamentally new ways. How to deal with these complex global issues is a major focus of this year's annual meeting of the American Association for the Advancement of Science (AAAS), whose theme is
Meeting Global Challenges: Discovery and Innovation
.
Heat Wave Forecasts Debut in Scorching Australia
Authors: Lewis Dyani
Published: February 2014

The Australian Bureau of Meteorology thinks it has hit upon a winning formula for converting forecasts of heat into a measure of the likely impact of heat waves on communities.
A Former Surgeon General Lends His Support to E-Cigarettes
Authors: Schmidt Charles
Published: February 2014

Former U.S. Surgeon General Richard Carmona explains how he became a supporter of electronic cigarettes.
As Lionfish Invade, Divers Defend Threatened Ecosystems
Authors: Pala Christopher
Published: February 2014

New studies are giving ecologists some hope of controlling red lionfish, a voracious predator that has invaded the Atlantic.
Subspecies Identification and Significance of 257 Clinical Strains of Mycobacterium avium
Authors: Tran Quynh T. , Han Xiang Y.
Published: February 2014

Mycobacterium avium
is abundant in the environment. It has four subspecies of three types: the human or porcine type,
M. avium
subsp.
hominissuis
; the bird type, including
M. avium
subsp.
avium
serotype 1 and serotype 2, 3 (also
M. avium
subsp.
silvaticum
); and the ruminant type,
M. avium
subsp.
paratuberculosis
. We determined the subspecies of 257
M. avium
strains isolated from patients at the M.D. Anderson Cancer Center from 2001 to 2010 and assessed their clinical significance. An assay of multiplex PCR was used for the typing. Results showed
M. avium
subsp.
hominissuis
to be most common (
n
= 238, 92.6%), followed by
M. avium
subsp.
avium
serotype 1 (
n
= 12, 4.7%) and serotype 2, 3 (
n
= 7, 2.7%). No strains of
M. avium
subsp.
paratuberculosis
were found. Of the 238 patients with
M. avium
subsp.
hominissuis
, 65 (27.3%) showed evidence of definite or probable infections, mostly in the respiratory tract, whereas the rest had weak evidence of infection. The bird-type subspecies, despite being infrequently isolated, caused relatively more definite and probable infections (10 of 19 strains, 52.6%). Overall, women of 50 years of age or older were more prone to
M. avium
infection than younger women or men of all ages were. We therefore conclude that
M. avium
subsp.
hominissuis
is the dominant
M. avium
subspecies clinically, that the two bird-type subspecies do cause human infections, and that
M. avium
infects mainly postmenopausal women. The lack of human clinical isolation of the ruminant type subspecies may need further investigation.
Diversity of Nontypeable Haemophilus influenzae Strains Colonizing Australian Aboriginal and Non-Aboriginal Children
Authors: Pickering J. , Smith-Vaughan H. , Beissbarth J. , Bowman J. M. , Wiertsema S. , Riley T. V. , Leach A. J. , Richmond P. , Lehmann D. , Kirkham L.-A.
Published: February 2014

Nontypeable
Haemophilus influenzae
(NTHI) strains are responsible for respiratory-related infections which cause a significant burden of disease in Australian children. We previously identified a disparity in NTHI culture-defined carriage rates between Aboriginal and non-Aboriginal children (42% versus 11%). The aim of this study was to use molecular techniques to accurately determine the true NTHI carriage rates (excluding other culture-identical
Haemophilus
spp.) and assess whether the NTHI strain diversity correlates with the disparity in NTHI carriage rates. NTHI isolates were cultured from 595 nasopharyngeal aspirates collected longitudinally from asymptomatic Aboriginal (
n
= 81) and non-Aboriginal (
n
= 76) children aged 0 to 2 years living in the Kalgoorlie-Boulder region, Western Australia. NTHI-specific 16S rRNA gene PCR and PCR ribotyping were conducted on these isolates. Confirmation of NTHI by 16S rRNA gene PCR corrected the NTHI carriage rates from 42% to 36% in Aboriginal children and from 11% to 9% in non-Aboriginal children. A total of 75 different NTHI ribotypes were identified, with 51% unique to Aboriginal children and 13% unique to non-Aboriginal children (
P
< 0.0001). The strain richness (proportion of different NTHI ribotypes) was similar for Aboriginal (19%, 65/346) and non-Aboriginal children (19%, 37/192) (
P
= 0.909). Persistent carriage of the same ribotype was rare in the two groups, but colonization with multiple NTHI strains was more common in Aboriginal children than in non-Aboriginal children. True NTHI carriage was less than that estimated by culture. The Aboriginal children were more likely to carry unique and multiple NTHI strains, which may contribute to the chronicity of NTHI colonization and subsequent disease.
Enhancers Are Major Targets for Murine Leukemia Virus Vector Integration
Authors: De Ravin Suk See , Su Ling , Theobald Narda , Choi Uimook , Macpherson Janet L. , Poidinger Michael , Symonds Geoff , Pond Susan M. , Ferris Andrea L. , Hughes Stephen H. , Malech Harry L. , Wu Xiaolin
Published: February 2014

Retroviral vectors have been used in successful gene therapies. However, in some patients, insertional mutagenesis led to leukemia or myelodysplasia. Both the strong promoter/enhancer elements in the long terminal repeats (LTRs) of murine leukemia virus (MLV)-based vectors and the vector-specific integration site preferences played an important role in these adverse clinical events. MLV integration is known to prefer regions in or near transcription start sites (TSS). Recently, BET family proteins were shown to be the major cellular proteins responsible for targeting MLV integration. Although MLV integration sites are significantly enriched at TSS, only a small fraction of the MLV integration sites (<15%) occur in this region. To resolve this apparent discrepancy, we created a high-resolution genome-wide integration map of more than one million integration sites from CD34
+
hematopoietic stem cells transduced with a clinically relevant MLV-based vector. The integration sites form ∼60,000 tight clusters. These clusters comprise ∼1.9% of the genome. The vast majority (87%) of the integration sites are located within histone H3K4me1 islands, a hallmark of enhancers. The majority of these clusters also have H3K27ac histone modifications, which mark active enhancers. The enhancers of some oncogenes, including LMO2, are highly preferred targets for integration without
in vivo
selection.

IMPORTANCE
We show that active enhancer regions are the major targets for MLV integration; this means that MLV preferentially integrates in regions that are favorable for viral gene expression in a variety of cell types. The results provide insights for MLV integration target site selection and also explain the high risk of insertional mutagenesis that is associated with gene therapy trials using MLV vectors.