bluuebunny/crossref_metadata_2025 huggingface dataset:
A Phase II Study of Trastuzumab Emtansine in Patients With Human Epidermal Growth Factor Receptor 2–Positive Metastatic Breast Cancer Who Were Previously Treated With Trastuzumab, Lapatinib, an Anthracycline, a Taxane, and Capecitabine
Authors: Krop Ian E. , LoRusso Patricia , Miller Kathy D. , Modi Shanu , Yardley Denise , Rodriguez Gladys , Guardino Ellie , Lu Michael , Zheng Maoxia , Girish Sandhya , Amler Lukas , Winer Eric P. , Rugo Hope S.
Published: May 2012

Purpose

To determine whether the antibody-drug conjugate trastuzumab emtansine (T-DM1), which combines human epidermal growth factor receptor 2 (HER2) –targeted delivery of the potent antimicrotubule agent DM1 with the antitumor activity of trastuzumab, is effective in patients with HER2-positive metastatic breast cancer (MBC) who have previously received all standard HER2-directed therapies.

Patients and Methods

In this single-arm phase II study, T-DM1 3.6 mg/kg was administered intravenously every 3 weeks to patients with HER2-positive MBC who had prior treatment with trastuzumab, lapatinib, an anthracycline, a taxane, and capecitabine. The primary objectives were overall response rate (ORR) by independent review and safety.

Results

Among 110 pretreated patients (median, seven prior agents for MBC; median follow-up, 17.4 months), the ORR was 34.5% (95% CI, 26.1% to 43.9%), clinical benefit rate was 48.2% (95% CI, 38.8% to 57.9%), median progression-free survival (PFS) was 6.9 months (95% CI, 4.2 to 8.4 months), and median duration of response was 7.2 months (95% CI, 4.6 months to not estimable). In patients with confirmed HER2-positive tumors (n = 80 by retrospective central testing), the response rate was 41.3% (95% CI, 30.4% to 52.8%), and median PFS was 7.3 months (95% CI, 4.6 to 12.3 months). Most adverse events were grades 1 to 2; the most frequent grade ≥ 3 events were thrombocytopenia (9.1%), fatigue (4.5%), and cellulitis (3.6%).

Conclusion

T-DM1 is well tolerated and has single-agent activity in patients with HER2-positive MBC who have previously received both approved HER2-directed therapies and multiple chemotherapy agents. T-DM1 may be an effective new treatment for this patient population.
Discordance Between Conclusions Stated in the Abstract and Conclusions in the Article: Analysis of Published Randomized Controlled Trials of Systemic Therapy in Lung Cancer
Authors: Altwairgi Abdullah K. , Booth Christopher M. , Hopman Wilma M. , Baetz Tara D.
Published: May 2012

Purpose

Clinicians may read only the abstract of an article to keep abreast of newly published randomized controlled trials (RCTs). However, discordances have been noticed in summary conclusions in the abstracts and the main body of some articles. This article evaluated such discordances in detail.

Methods

RCTs of systemic therapy for lung cancer published between 2004 and 2009 were considered. Conclusions in the body of the articles and those in the abstracts were graded by using a 7-point Likert scale; 1 for strong endorsement of the control arm, 4 for a neutral statement, and 7 for strong endorsement of the experimental arm. Conclusions were classified as discordant if the difference in scores was ≥ 2. χ2 tests and logistic regression were used to identify factors associated with discordance.

Results

From among 114 eligible RCTs identified (90 for non–small-cell and 24 for small-cell lung cancer), 11 (10%) articles presented discordant conclusions in the abstract and in the body of the articles. Discordance was most common when the experimental arm was strongly supported in the abstract but not in the body of the article (nine of 11; 82%); however, the converse was much less common (two of 11; 18%; P < .001). Intraclass correlations for the two reviewers were ≥ 0.9. The discordances were found to be independent of trial-related factors.

Conclusion

Conclusive statements in the abstract can differ from those in the full text. Clinicians should use caution when they consider making changes in their practice on the basis of reading only the abstract of a published RCT.
Enantioselective Ring-Opening Reaction of Epoxides with MeOH Catalyzed by Homochiral Metal–Organic Framework
Authors: Tanaka Koichi , Otani Ken-ichi , Murase Takanori , Nishihote Shyota , Urbanczyk-Lipkowska Zofia
Published: May 2012

Two new copper metal–organic frameworks containing 2,2′-dihydroxy-1,1′-binaphthalene-5,5′-dicarboxylic acid (5,5′-H2BDA) and 2,2′-dihydroxy-1,1′-binaphthalene-4,4′-dicarboxylic acid (4,4′-H2BDA) have been prepared. X-ray structure determination of [Cu2(5,5′-BDA)2(H2O)2]·MeOH·2H2O (MOF-1) and [Cu2(4,4′-BDA)2(H2O)2]·4H2O (MOF-2) revealed similar 2D sheet structures, containing square-grid coordination networks, but differences in the stacking motif. The desolvated MOF-1 and -2 were used as Lewis acid catalysts in the asymmetric ring-opening reaction of epoxides with MeOH.
Solid-State Photochromism of 5-tert-Butyl-2-hydroxyisophthalaldehyde
Authors: Tanaka Koichi , Watanabe Yuta , Kalicki Przemysaw , Urbanczyk-Lipkowska Zofia
Published: May 2012

Colorless crystals of 5-tert-butyl-2-hydroxyisophthalaldehyde change to an orange-red color upon brief exposure to UV–vis radiation (λ > 300 nm). The colored crystals revert to colorless in the dark. X-ray diffraction revealed different packing patterns for the crystals of nonphotochromic and photochromic compounds.
Development of Novel and Highly Efficient Methods to Construct Carbon–Carbon Bonds Using Group 7 Transition-Metal Catalysts
Authors: Kuninobu Yoichiro , Takai Kazuhiko
Published: May 2012

Rhenium- or manganese-catalyzed transformations based on the cleavage of inactive bonds, such as carbon–hydrogen and carbon–carbon bonds are discussed. Such transformations are recognized as key methods to realize efficient and powerful reactions. We also reveal novel regio- and/or stereodefined cycloaddition reactions using a rhenium or manganese catalyst. Most of the catalytic activities are typical of rhenium and manganese carbonyl complexes.
Kinetic Assessment and Numerical Modeling of Photocatalytic Water Splitting toward Efficient Solar Hydrogen Production
Authors: Hisatomi Takashi , Minegishi Tsutomu , Domen Kazunari
Published: May 2012

Photocatalytic water splitting has been studied extensively as a promising technology for scalable and cost-efficient hydrogen production using solar energy. Although overall water splitting has been achieved under visible light irradiation, significant progress in reaction efficiencies at longer wavelengths is needed to enable practical solar energy conversion. This article reports recent advancements in kinetic investigation and numerical modeling of photocatalytic water splitting to understand problems with existing photocatalysts and develop strategies to boost the reaction efficiency. Kinetic investigation based on cocatalyst loading, light intensity, hydrogen/deuterium isotopes, and reaction temperature suggests that the majority of photoexcited carriers recombine before contributing to the water splitting reaction on the surface in most cases, and that improvement in semiconducting properties of photocatalysts by decreasing defect and donor concentrations is beneficial to boost photocatalytic performance. It is demonstrated that an appropriate material design to suppress generation of donor species actually improves photocatalytic activity. Numerical modeling of steady state carrier concentrations suggests that an asymmetric built-in potential in photocatalyst particles enhances charge separation and thus extends the lifetimes of photoexcited carriers. On the basis of the recent findings, we suggest strategies to improve the reaction efficiency of photocatalytic water splitting.
Competence in health care: an abilities-based versus a pathology-based approach
Authors: Meynen Gerben , Widdershoven Guy
Published: May 2012

Competence is central to informed consent and, therefore, to medical practice. In this context, competence is regarded as synonymous with decision-making capacity. There is wide consensus that competence should be approached conceptually by identifying the abilities needed for decision-making capacity. Incompetence, then, is understood as a condition in which certain abilities relevant to decision-making capacity are lacking. This approach has been helpful both in theory and practice. There is, however, another approach to incompetence, namely to relate it to mental disorder. This approach has been followed in recent research that has shown, for instance, that in anorexia nervosa a person's values may be changed, resulting in ‘pathological’ values. We explore some advantages and disadvantages of both abilities-based and pathology-based approaches. We argue that both can be valuable for further clarification of the concept of competence and improving clinical practice. Given the current predominance of the abilities-based approach, we make a plea for a greater focus on pathology-based practice and research.
The 2012 report of the Commission on Assisted Dying: providing assistance in the debate that will not die?
Authors: Brassington Iain
Published: May 2012

The Commission on Assisted Dying was an unofficial body set up to investigate the legal position on assisted dying in the UK in the autumn of 2010. Its report was published to some degree of media attention in the first week of January 2012; its most headline-grabbing suggestion provided a framework setting out how British law might be reformed to allow assisted dying for the terminally ill. In this paper, I analyse some of the key points of the report and argue that it adds little that could settle – or even add to – the assisted dying debate.
Challenging some myths about the right to life at the end of life. 2: Reinstating the ethically excluded
Authors: Wicks Elizabeth
Published: May 2012

This article continues the rejection of certain myths about the right to life at the end of life commenced in an article in the previous issue of the journal Clinical Ethics. It focuses upon ethical arguments that seek to exclude two categories of human beings from the usual protection of human life: those described as ‘non-persons’ and those ‘designated for death’. The article argues that, while the protection offered to life by means of the right to life is far from absolute, the right remains applicable to all human beings, irrespective of their life expectancy or mental capacity.
Tuberculous choroidal granuloma in an HIV-positive patient
Authors: Papineni P , Saunders J , Papageorgiou K , Westcott M , Noble H
Published: May 2012

We report a case of a 34-year-old HIV-positive patient undergoing treatment for pulmonary and lymph node Mycobacterium tuberculosis infection, who developed loss of vision secondary to a tuberculous choroidal granuloma.
A case series of the management of symptomatic azole-resistant candida
Authors: Challenor R , Pinsent S , Ekanayaka R
Published: May 2012

Patients with symptomatic azole-resistant Candida albicans or non- albicans candida are difficult to manage. Treatment is largely anecdotal due to the relatively small number of patients. We present six case reports which highlight our own observation in clinical practice including four patients who were treated successfully with topical amphotericin B/flucytosine vaginal gel for 14 days (Stoke-on-Trent formula).
Calvarial syphilis in an HIV-positive man
Authors: Toby M , Larbalestier N , Kulasegaram R , Teague A , Conway K , White J
Published: May 2012

Bone involvement in secondary and tertiary syphilis is a well-documented but unusual phenomenon. We report the case of an atypical presentation of secondary syphilis in a 25-year-old HIV-positive man who has sex with men. He presented initially with headaches and an unusual calvarial swelling. The skull findings were consistent with osteitis and he later developed systemic symptoms. Treponema pallidum serology was positive and the lesions and systemic symptoms resolved completely after administration of appropriate antibiotic therapy.
Clinical and social determinants of diarrhoeal disease in a rural HIV/AIDS clinic, South Africa: a case-control study
Authors: Moshabela M , MacPherson P , Ezard N , Frean E , Mashimbye L , Elliott J H , Oldenburg B
Published: May 2012

Diarrhoeal diseases are a common cause of morbidity and are associated with mortality in HIV-infected populations. Little is known about the contribution of clinical and socio-environmental factors to the risk of diarrhoea in these populations in rural sub-Saharan Africa. We conducted a case-control study of people attending a rural HIV clinic with an episode of diarrhoea in Bushbuckridge, South Africa. Cases were defined as HIV-positive adults with symptoms of diarrhoea before or after initiation of antiretroviral therapy (ART). Controls without diarrhoea were randomly selected from clinic attendees. Structured questionnaires and case-file reviews were undertaken to describe clinical and socioenvironmental risk factors. We recruited 103 cases of diarrhoea from 121 patients meeting case definitions. Cases were more likely to be women ( P = 0.013), aged over 45 years ( P = 0.002), divorced or separated ( P = 0.006), have limited formal education ( P = 0.003), have inadequate access to sanitation facilities ( P = 0.045), have water access limited to less than three days per week ( P = 0.032) and not yet initiated on ART ( P < 0.001). In multivariate analysis, diarrhoea remained associated with female gender (adjusted odds ratio [aOR]: 2.02, 95% CI 1.10–3.73), older age (aOR: 6.31, 95% CI 1.50–26.50), limited access to water (aOR: 2.66, 95% CI 1.32–5.35) and pre-ART status (aOR: 5.87, 95% CI 3.05–11.27). Clinical and socio-environmental factors are associated with occurrence of diarrhoeal disease among rural HIV patients in South Africa. Further intervention research is urgently needed, combining community- and clinic-based approaches, to improve access to water, sanitation and ART for rural areas with high HIV prevalence, along with structural interventions to address gender inequities.
Therapeutic combination of radiofrequency surgical dissection and oral acitretin in the management of perianal Buschke–Löwenstein tumour: a case report
Authors: Mavrogianni P , Fallidas E , Nicolaidou E , Villias K , Stefanaki I , Katsambas A , Lira T , Apostolopoulos P , Androne I , Rouvas G , Tsibouris P , Alexandrakis G
Published: May 2012

Giant condyloma acuminatum (GCA), or Buschke–Löwenstein tumour (BLT), is a rare large tumour of the anogenital area. It is caused by human papillomavirus genotypes 6 and 11, and it is characterized by aggressive local invasion and frequent recurrences after treatment. Treatment of choice is radical excision, although chemotherapy and radiation are also used in special cases. We report a case of a young man with anogenital GCA, presenting with a large perianal mass and pain during defaecation. The patient was treated by surgical removal of almost the entirety of the mass, using radiofrequency surgical dissection. The concurrent use of oral acitretin for the treatment of erythrodermic psoriasis led to elimination of the remaining disease. The patient remains free of disease 26 months after the end of treatment.
Short-course intravenous aciclovir treatment for cutaneous herpes zoster in patients with HIV infection
Authors: Noonan L , Gunson T , Ellis-Pegler R , Thomas M , Briggs S
Published: May 2012

There are no comparative data on the treatment duration of cutaneous herpes zoster (HZ) in patients with HIV infection. We retrospectively reviewed all 51 adult patients with HIV infection presenting with cutaneous HZ in the 15-year period 1995–2009 treated with intravenous aciclovir alone. The median CD4 count was 297 (range 10–703) cells/mm3. There were 44 episodes of localized and seven episodes of disseminated cutaneous HZ. Patients received a median of nine (range 3–17) doses of intravenous aciclovir given at a median dose of 6.5 (range 2.9–10.8) mg/kg eight hourly. One patient (2%) relapsed early and four patients (7.8%) relapsed late with further episodes of cutaneous HZ. Seven patients (13.7%) developed postherpetic neuralgia. Three days of intravenous aciclovir is effective treatment for cutaneous HZ in patients with HIV infection.
Patient views on examinations as part of asymptomatic screening in sexual health clinics
Authors: Heseltine K , Foley E , Alborough B , Patel R
Published: May 2012

Examinations of asymptomatic patients (AP) do not always take place in sexual health clinics, partly due to the evidence that clinically significant findings (not identified by urine and blood tests) are rarely found on examination of these patients. However, it is unclear from the literature as to whether patients, given the option, would choose to be examined when fully aware of what may be identified on examination as well as the frequency of positive findings. A total of 110 men attending a sexual health clinic who self-identified as asymptomatic were given a patient information sheet (PIS) describing the place and value (if any) of examinations in AP and were asked if they would like an examination. Of the 83 truly asymptomatic men with low sexual risk involved, 86% expressed the intention of having an examination having read the PIS.
HIV-1 drug resistance at virological failure versus immunological failure among patients failing first-line antiretroviral therapy in a resource-limited setting
Authors: Sungkanuparph S , Win M M , Kiertiburanakul S , Phonrat B , Maek-a-nantawat W
Published: May 2012

Antiretroviral treatment failure has been defined by immunological failure (IF) in some resource-limited settings whereas defining by virological failure (VF) has been widely used in developed countries. There is limited comparison of the levels of HIV-1 drug resistance between using VF and IF for the diagnosis of treatment failure. A retrospective cohort study was conducted among HIV-1-infected patients failing first-line antiretroviral therapy (ART). Of 95 patients, median CD4 and HIV-1 RNA were 158 cells/mm3 and 10,200 copies/mL, respectively. Patients in the IF group had higher HIV-1 RNA than those in VF group (23,820 versus 9510 copies/mL, P = 0.008). Nucleoside reverse transcriptase inhibitor (NRTI)-, non-NRTI- and protease inhibitor-resistance-associated mutations (RAMs) were observed in 57.9%, 94.7% and 5.3%, respectively. Q151M, a multidrug RAM, was more commonly observed in the IF group (14.8% versus 2.9%, P = 0.032). Using IF to diagnose treatment failure is associated with higher HIV-1 RNA levels and a higher rate of Q151M, which can limit the options for second-line ART.
Performance against local service quality indicators: re-setting the indicators
Authors: Challenor R , Warwick Z , Ekanayaka R
Published: May 2012

Local service quality indicators (SQIs) both for genitourinary medicine and HIV were drafted following patient and public involvement in 2009. At that time there were few published data to help in setting some of the original SQIs. Our clinical performance was audited against these SQIs in 2009 and subsequently re-audited in 2010 and 2011. The SQIs were revised based upon the results of the three audits. This paper attempts to explain the revisions based upon the audits. Commissioners are currently working with service providers around the country to develop HIV clinical outcome indicators that link payment to performance. It is vital to ensure that clinical outcome indicators are set correctly so that they are challenging but still achievable. We hope other services may wish to audit performance against our revised measures. If such data were to be pooled this could provide evidence for more robust benchmarking.
Causes of first hospitalization among 1121 HIV-infected children: comparison of the pre-Pneumocystis jiroveci pneumonia prophylaxis, pre-antiretroviral therapy and antiretroviral therapy periods
Authors: Sudjaritruk T , Oberdorfer P , Puthanakit T , Sirisanthana T , Sirisanthana V
Published: May 2012

This study identified causes of first hospitalization among perinatally acquired HIV-infected children at Chiang Mai University Hospital between 1989 and 2009. Data were stratified into three seven-year time periods: pre- Pneumocystis jiroveci pneumonia (PJP) prophylaxis, pre-antiretroviral therapy (ART) and ART period. Over the 21-year study period, 1121 children were hospitalized. The mean age at admission was 2.7 years and had become older over time. Of the 1121 hospitalization causes, 50.6% were AIDS-defining illnesses (ADIs), 48.1% were non-AIDS-defining illnesses (NADIs) and 1.3% were related to immune reconstitution syndrome. Types of ADIs changed over time: PJP and recurrent Salmonella septicaemia decreased, while mycobacterial infection and systemic fungal infection increased. For NADIs, bacterial infections, viral infections and gastrointestinal problems decreased, but haematological problems increased in the third period. Decline in the number of hospitalizations and mortality rate, increase in the mean age of hospitalized children, change in the distribution of specific illnesses and appearance of immune reconstitution syndrome were observed in the ART period.
Weekend Arthroplasty: A Longer Inpatient Stay?
Authors: Gibbs D , Tafazal S , Handley R , Newey M
Published: May 2012

As pressures mount on efficiency, hip and knee arthroplasty surgery is increasingly being performed during weekends. Despite the growing trend for weekend orthopaedic surgery, there are virtually no published data on the effect of weekend operating on the length of hospital stay (LOS).
Hamstring Avulsion Injuries
Authors: Benjamin-Laing H , Fayad T , Haddad FS
Published: May 2012

Times have changed since the Olympic Games in 1896, where 241 athletes representing 14 nations competed. The Beijing Olympics in 2008 included 10,977 athletes from more than 200 nations. The Olympic Games are the biggest multisport event and often represent the pinnacle of an athlete's career. Olympic and sporting history is full of tales of woe from athletes who have been unfortunate to experience an injury to the lower extremity during an event. 10% of athletes competing at the Beijing Olympic games in 2008 sustained injuries with 50% of these injuries preventing the athletes from participating in competition or training. Similar percentages have been reported in disabled athletes during the Paralympic Games. Half of these injuries may affect the lower limb and in explosive athletes with large muscle groups around the pelvis, hamstring avulsions are more common.
Saints and sinners: John Abernethy
Authors: King Louise
Published: May 2012

John Abernethy (1764–1831), was one of the best-known surgeons of his generation. He was instrumental in the founding of the medical school at St Bartholomew's Hospital, despite not demonstrating great skill as a surgeon and largely because he was an eccentric and compelling lecturer who drew crowds. Yet he was also a difficult man who embraced and promoted the nepotism of the time by favouring former pupils over those from outside his sphere of influence.
The Athlete's Shoulder: When Not to Operate
Authors: Funk Lennard
Published: May 2012

Athletes present unique challenges in that their demands are highly specific to their sport and activity. Many sports and positions place extreme demands on the shoulder and the mechanisms of injury may be highly specific to a particular sport. Unique injury patterns are associated with certain sports, for example: swimmer's shoulder, volleyball shoulder, rugby shoulder and so on. Additionally, most sports are seasonal – hence the injuries and treatments associated with the sport will be too. There is a lot of anxiety around a professional athlete's injury, not only from the athletes themselves but also from their coaches, dependents and their sports agent. The decision to operate on an athlete should never be taken lightly and generally always involves a multi-disciplinary approach including the surgeon, team therapist and team doctor.
RCS promotes musical theatre
Authors: Williams Esther
Published: May 2012

Easy listening music in the operating theatre could reduce anxiety for millions of patients undergoing operations using local anaesthetic each year, according to research. This is just one of the surgical news stories that captured the media's imagination last month. Surgeons from the plastic and reconstructive department at the John Radcliffe Hospital in Oxford measured the respiratory rates of emergency patients and asked them to rate their feelings of worry. Half the patients had their operation in a theatre with music playing and half without – the group who were exposed to music reported lower levels of anxiety and had a lower breathing rate.
What do we know and how well do we know it? Identifying practice-based insights in education
Authors: Miller Barbara , Pasley Joan
Published: May 2012

Knowledge derived from practice forms a significant portion of the knowledge base in the education field, yet is not accessible using existing empirical research methods. This paper describes a systematic, rigorous, grounded approach to collecting and analysing practice-based knowledge using the authors’ research in teacher leadership as an example. Practitioners with relevant experience and expertise participated in multi-round, online panels in which they responded to several types of items, culminating in ‘advice to the field’. Strategies used for sampling, panel implementation, and analysis are described for identifying practice-based insights that are useful to practitioners, policy makers and researchers.
Communicating social research findings more effectively: what can we learn from other fields?
Authors: Davies Huw T.O. , Powell Alison E.
Published: May 2012

Many of the practices around the sharing of social research are stuck in ‘information-telling’ mode and fail to draw on approaches from other fields that are concerned with influencing deeper beliefs, values, assumptions or mental models. This paper seeks to scope out some of these other areas of ‘influencing’ to consider their relevance for the communication of social research. We conclude that, despite some attendant risks, there is scope for using a wider repertoire of approaches to communicating social research findings.
What is Quality? An Integrative Framework of Processes and States
Authors: Golder Peter N. , Mitra Debanjan , Moorman Christine
Published: May 2012

Quality is a central element in business strategy and academic research. Despite important research on quality, an opportunity for an integrative framework remains. The authors present an integrative framework of quality that captures how firms and customers produce quality (the quality production process), how firms deliver and customers experience quality (the quality experience process), and how customers evaluate quality (the quality evaluation process). The framework extends the literature in several ways. First, the authors describe important linkages between the three processes, including links reflecting the role of co-production. Second, they point to overlooked aspects of the quality processes that influence how quality is conceptualized and should be managed. These include customer heterogeneity in measurement knowledge and motivation; the role of emotion in quality production, experience, and evaluation; and a new typology of attributes. Third, they propose a quality state residing within each quality process and describe what gives rise to these states, which will enhance decision makers’ ability to measure and manage quality processes. Finally, they offer theoretical and managerial implications derived from their integrative quality framework including 20 strategies to increase customer satisfaction.
Nerve Growth Factor in the Hippocamposeptal System: Evidence for Activity-Dependent Anterograde Delivery and Modulation of Synaptic Activity
Authors: Guo Lan , Yeh Mason L. , Carlson Verginia C. Cuzon , Johnson-Venkatesh Erin M. , Yeh Hermes H.
Published: May 2012

Neurotrophins have been implicated in regulating neuronal differentiation, promoting neuronal survival, and modulating synaptic efficacy and plasticity. The prevailing view is that, depending on the target and mode of action, most neurotrophins can be trafficked and released either anterogradely or retrogradely in an activity-dependent manner. However, the prototypic neurotrophin, nerve growth factor (NGF), is not thought to be anterogradely delivered. Here we provide the neuroanatomical substrate for an anterograde hippocamposeptal transport of NGF by demonstrating its presence in mouse hippocampal GABAergic neurons and in their hippocamposeptal axons that ramify densely and abut neurons in the medial septum/diagonal band of Broca (MS/DB). We also demonstrate an activity-dependent increase in septal NGF levels that is dependent on the pattern of intrahippocampal stimulation. In addition, we show that acute exposure to NGF, via activation of TrkA, attenuates GABAAreceptor-mediated inhibitory synaptic currents and reduces sensitivity to exogenously applied GABA. These acute actions of NGF display cell type and functional selectivity insofar as (1) they were found in cholinergic, but not GABAergic, MS/DB neurons, and (2) glutamate-mediated excitatory synaptic activity as well as AMPA-activated current responses were unaffected. Our results advocate a novel anterograde, TrkA-mediated NGF signaling in the CNS.
Corticosteroid-Dependent Plasticity Mediates Compulsive Alcohol Drinking in Rats
Authors: Vendruscolo Leandro F. , Barbier Estelle , Schlosburg Joel E. , Misra Kaushik K. , Whitfield Timothy W. , Logrip Marian L. , Rivier Catherine , Repunte-Canonigo Vez , Zorrilla Eric P. , Sanna Pietro P. , Heilig Markus , Koob George F.
Published: May 2012

Alcoholism is characterized by a compulsion to seek and ingest alcohol, loss of control over intake, and the emergence of a negative emotional state during abstinence. We hypothesized that sustained activation of neuroendocrine stress systems (e.g., corticosteroid release via the hypothalamic-pituitary-adrenal axis) by alcohol intoxication and withdrawal and consequent alterations in glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) activation drive compulsive alcohol drinking. Our results showed that rats exposed to alcohol vapor to the point of dependence displayed increased alcohol intake, compulsive drinking measured by progressive-ratio responding, and persistent alcohol consumption despite punishment, assessed by adding quinine to the alcohol solution, compared with control rats that were not exposed to alcohol vapor. No group differences were observed in the self-administration of saccharin-sweetened water. Acute alcohol withdrawal was accompanied by downregulated GR mRNA in various stress/reward-related brain regions [i.e., prefrontal cortex, nucleus accumbens (NAc), and bed nucleus of the stria terminalis (BNST)], whereas protracted alcohol abstinence was accompanied by upregulated GR mRNA in the NAc core, ventral BNST, and central nucleus of the amygdala. No significant alterations in MR mRNA levels were found. Chronic GR antagonism with mifepristone (RU38486) prevented the escalation of alcohol intake and compulsive responding induced by chronic, intermittent alcohol vapor exposure. Chronic treatment with mifepristone also blocked escalated alcohol drinking and compulsive responding during protracted abstinence. Thus, the GR system appears to be involved in the development of alcohol dependence and may represent a potential pharmacological target for the treatment of alcoholism.
Similar Effects of Feature-Based Attention on Motion Perception and Pursuit Eye Movements at Different Levels of Awareness
Authors: Spering Miriam , Carrasco Marisa
Published: May 2012

Feature-based attention enhances visual processing and improves perception, even for visual features that we are not aware of. Does feature-based attention also modulate motor behavior in response to visual information that does or does not reach awareness? Here we compare the effect of feature-based attention on motion perception and smooth-pursuit eye movements in response to moving dichoptic plaids—stimuli composed of two orthogonally drifting gratings, presented separately to each eye—in human observers. Monocular adaptation to one grating before the presentation of both gratings renders the adapted grating perceptually weaker than the unadapted grating and decreases the level of awareness. Feature-based attention was directed to either the adapted or the unadapted grating's motion direction or to both (neutral condition). We show that observers were better at detecting a speed change in the attended than the unattended motion direction, indicating that they had successfully attended to one grating. Speed change detection was also better when the change occurred in the unadapted than the adapted grating, indicating that the adapted grating was perceptually weaker. In neutral conditions, perception and pursuit in response to plaid motion were dissociated: While perception followed one grating's motion direction almost exclusively (component motion), the eyes tracked the average of both gratings (pattern motion). In attention conditions, perception and pursuit were shifted toward the attended component. These results suggest that attention affects perception and pursuit similarly even though only the former reflects awareness. The eyes can track an attended feature even if observers do not perceive it.
Serum Response Factor and cAMP Response Element Binding Protein Are Both Required for Cocaine Induction of ΔFosB
Authors: Vialou Vincent , Feng Jian , Robison Alfred J. , Ku Stacy M. , Ferguson Deveroux , Scobie Kimberly N. , Mazei-Robison Michelle S. , Mouzon Ezekiell , Nestler Eric J.
Published: May 2012

The molecular mechanism underlying induction by cocaine of ΔFosB, a transcription factor important for addiction, remains unknown. Here, we demonstrate a necessary role for two transcription factors, cAMP response element binding protein (CREB) and serum response factor (SRF), in mediating this induction within the mouse nucleus accumbens (NAc), a key brain reward region. CREB and SRF are both activated in NAc by cocaine and bind to thefosBgene promoter. Using viral-mediated Cre recombinase expression in the NAc of single- or double-floxed mice, we show that deletion of both transcription factors from this brain region completely blocks cocaine induction of ΔFosB in NAc, whereas deletion of either factor alone has no effect. Furthermore, deletion of both SRF and CREB from NAc renders animals less sensitive to the rewarding effects of moderate doses of cocaine when tested in the conditioned place preference (CPP) procedure and also blocks locomotor sensitization to higher doses of cocaine. Deletion of CREB alone has the opposite effect and enhances both cocaine CPP and locomotor sensitization. In contrast to ΔFosB induction by cocaine, ΔFosB induction in NAc by chronic social stress, which we have shown previously requires activation of SRF, is unaffected by the deletion of CREB alone. These surprising findings demonstrate the involvement of distinct transcriptional mechanisms in mediating ΔFosB induction within this same brain region by cocaine versus stress. Our results also establish a complex mode of regulation of ΔFosB induction in response to cocaine, which requires the concerted activities of both SRF and CREB.
Object Ensemble Processing in Human Anterior-Medial Ventral Visual Cortex
Authors: Cant Jonathan S. , Xu Yaoda
Published: May 2012

Our visual system can extract summary statistics from large collections of similar objects without forming detailed representations of the individual objects in the ensemble. Such object ensemble representation is adaptive and allows us to overcome the capacity limitation associated with representing specific objects. Surprisingly, little is known about the neural mechanisms supporting such object ensemble representation. Here we showed human observers identical photographs of the same object ensemble, different photographs depicting the same ensemble, or different photographs depicting different ensembles. We observed fMRI adaptation in anterior-medial ventral visual cortex whenever object ensemble statistics repeated, even when local image features differed across photographs. Interestingly, such object ensemble processing is closely related to texture and scene processing in the brain. In contrast, the lateral occipital area, a region involved in object–shape processing, showed adaptation only when identical photographs were repeated. These results provide the first step toward understanding the neural underpinnings of real-world object ensemble representation.
The Diffusion Tensor Imaging Toolbox
Authors: Alger Jeffry R.
Published: May 2012

During the past few years,The Journal of Neurosciencehas published more than 30 articles that describe investigations that used Diffusion Tensor Imaging (DTI) and related techniques as a primary observation method. This illustrates a growing interest in DTI within the basic and clinical neuroscience communities. This article summarizes DTI methodology in terms that can be immediately understood by the neuroscientist who has little previous exposure to DTI. It describes the fundamentals of water molecular diffusion coefficient measurement in brain tissue and illustrates how these fundamentals can be used to form vivid and useful depictions of white matter macroscopic and microscopic anatomy. It also describes current research applications and the technique's attributes and limitations. It is hoped that this article will help the readers of thisJournalto more effectively evaluate neuroscience studies that use DTI.
Gamma-Band Oscillations in the Primary Somatosensory Cortex—A Direct and Obligatory Correlate of Subjective Pain Intensity
Authors: Zhang Z. G. , Hu L. , Hung Y. S. , Mouraux A. , Iannetti G. D.
Published: May 2012

Electroencephalographic gamma band oscillations (GBOs) induced over the human primary somatosensory cortex (SI) by nociceptive stimuli have been hypothesized to reflect cortical processing involved directly in pain perception, because their magnitude correlates with pain intensity. However, as stimuli perceived as more painful are also more salient, an alternative interpretation of this correlation is that GBOs reflect unspecific stimulus-triggered attentional processing. In fact, this is suggested by recent observations that other features of the electroencephalographic (EEG) response correlate with pain perception when stimuli are presented in isolation, but not when their saliency is reduced by repetition. Here, by delivering trains of three nociceptive stimuli at a constant 1 s interval, and using different energies to elicit graded pain intensities, we demonstrate that GBOs recorded over SI always predict the subjective pain intensity, even when saliency is reduced by repetition. These results provide evidence for a close relationship between GBOs and the cortical activity subserving pain perception.
Response of Dorsomedial Prefrontal Cortex Predicts Altruistic Behavior
Authors: Waytz Adam , Zaki Jamil , Mitchell Jason P.
Published: May 2012

Human beings have an unusual proclivity for altruistic behavior, and recent commentators have suggested that these prosocial tendencies arise from our unique capacity to understand the minds of others (i.e., to mentalize). The current studies test this hypothesis by examining the relation between altruistic behavior and the reflexive engagement of a neural system reliably associated with mentalizing. Results indicated that activity in the dorsomedial prefrontal cortex—a region consistently involved in understanding others' mental states—predicts both monetary donations to others and time spent helping others. These findings address long-standing questions about the proximate source of human altruism by suggesting that prosocial behavior results, in part, from our broader tendency for social-cognitive thought.
Prefrontal Neurons Represent Winning and Losing during Competitive Video Shooting Games between Monkeys
Authors: Hosokawa Takayuki , Watanabe Masataka
Published: May 2012

Humans and animals must work to support their survival and reproductive needs. Because resources are limited in the natural environment, competition is inevitable, and competing successfully is vitally important. However, the neuronal mechanisms of competitive behavior are poorly studied. We examined whether neurons in the lateral prefrontal cortex (LPFC) showed response sensitivity related to a competitive game. In this study, monkeys played a video shooting game, either competing with another monkey or the computer, or playing alone without a rival. Monkeys performed more quickly and more accurately in the competitive than in the noncompetitive games, indicating that they were more motivated in the competitive than in the noncompetitive games. LPFC neurons showed differential activity between the competitive and noncompetitive games showing winning- and losing-related activity. Furthermore, activities of prefrontal neurons differed depending on whether the competition was between monkeys or between the monkey and the computer. These results indicate that LPFC neurons may play an important role in monitoring the outcome of competition and enabling animals to adapt their behavior to increase their chances of obtaining a reward in a socially interactive environment.
Type 2 diabetes from pediatric to geriatric age: analysis of gender and obesity among 120 183 patients from the German/Austrian DPV database
Authors: Awa Wendy L , Fach E , Krakow D , Welp R , Kunder J , Voll A , Zeyfang A , Wagner C , Schütt M , Boehm B , de Souza M , Holl R W
Published: May 2012

Aim

To characterize the clinical phenotype of type 2 diabetes mellitus (T2DM) with respect to age, gender, and BMI.

Method

Anonymized data of 120 183 people with T2DM from the German/Austrian multicenter Diabetes Patienten Verlaufsdokumentation database were analyzed based on chronological age or age at diagnosis (0–19, 20–39, 40–59, 60–79, and ≥80 years). Age, gender, and BMI comparisons with clinical phenotype were made using χ2 and Kruskal–Wallis tests (SAS V9.2).

Results

Of all the patients, 51.3% were male, average age was 67.1±12.7 years, and average disease duration was 9.9±9.1 years. More girls than boys were diagnosed during adolescence and more men than women during adulthood (20–60 years). No gender differences existed when age at diagnosis was ≥60 years. Patients were obese on average (BMI: 30.5±6.1 kg/m2) and had significantly higher BMI values than German population peers. The BMI gap was widest in the younger age categories and closed with increasing age. Adult women were significantly more obese than men. Obese patients more often had elevated HbA1c (≥7.5%), hypertension or dyslipidemia (irrespective of age), microalbuminuria (adults), or retinopathy (elderly) than nonobese patients. More men than women (20–60 years) had hypertension, dyslipidemia, or microalbuminuria while more women than men (≥60 years) had hypertension or dyslipidemia.

Conclusion

During puberty, more girls than boys were diagnosed with T2DM while during adulthood males predominated. T2DM manifested at comparatively lower BMI in males, and younger patients were more obese at diagnosis. Age, gender, and BMI were also associated with poor metabolic control and cardiovascular disease comorbidities/complications.
Neuroendocrine tumor disease: an evolving landscape
Authors: Frilling Andrea , Åkerström Goran , Falconi Massimo , Pavel Marianne , Ramos Jose , Kidd Mark , Modlin Irvin Mark
Published: May 2012

Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) represent a heterogenous group of tumors arising from a variety of neuroendocrine cell types. The incidence and prevalence of GEP-NENs have markedly increased over the last three decades. Symptoms are often absent in early disease, or vague and nonspecific even in advanced disease. Delayed diagnosis is thus common. Chromogranin A is the most commonly used biomarker but has limitations as does the proliferative marker Ki-67%, which is often used for tumor grading and determination of therapy. The development of a multidimensional prognostic nomogram may be valuable in predicting tumor behavior and guiding therapy but requires validation. Identification of NENs that express somatostatin receptors (SSTR) allows for SSTR scintigraphy and positron emission tomography imaging using novel radiolabeled compounds. Complete surgical resection of limited disease or endoscopic ablation of small lesions localized in stomach or rectum can provide cure; however, the majority of GEP-NENs are metastatic (most frequently the liver and/or mesenteric lymph nodes) at diagnosis. Selected patients with metastatic disease may benefit from advanced surgical techniques including hepatic resection or liver transplantation. Somatostatin analogs are effective for symptomatic treatment and exhibit some degree of antiproliferative activity in small intestinal NENs. There is a place for streptozotocin, temozolomide, and capecitabine in the management of pancreatic NENs, while new agents targeting either mTOR (everolimus) or angiogenic (sunitinib) pathways have shown efficacy in these lesions.
Micro-structural and compositional variations of hydrothermal epidote-group minerals from a peralkaline granite, Corupá Pluton, Graciosa Province, South Brazil, and their petrological implications
Authors: Vlach Silvio R.F.
Published: May 2012

Epidote-group minerals, together with albite, quartz, fluorite, Al-poor and Fe-rich phyllosilicates, zircon, and minor oxides and sulphides, are typical hydrothermal phases in peralkaline alkali-feldspar granites from the Corupá Pluton, Graciosa Province, South Brazil. The epidote-group minerals occur as single crystals and as aggregates filling in rock interstices and miarolitic cavities. They display complex recurrent zoning patterns with an internal zone of ferriallanite-(Ce), followed by allanite-(Ce), then epidote-ferriepidote, and an external zone with allanite-(Ce), with sharp limits, as shown in BSE and X-ray images. REE patterns show decreasing fractionation degrees of LREE over HREE from ferriallanite to epidote. The most external allanite is enriched in MREE. LA-ICP-MS data indicate that ferriallanite is enriched (>10-fold) in Ti, Sr and Ga, and depleted in Mg, Rb, Th and Zr relative to the host granite. Allanite has lower Ga and Mn and higher Zr, Nb and U contents as compared to ferriallanite, while epidote is enriched in Sr, U and depleted in Pb, Zr, Hf, Ti and Ga. The formation of these minerals is related to the variable concentrations of HFSE, Ca, Al, Fe and F in fluids remaining from magmatic crystallization, in an oxidizing environment, close to the HM buffer. L-MREE were in part released by the alteration of chevkinite, their main primary repository in the host rocks.
A comparative expression analysis of gene transcripts in brain tissue of non-transgenic and GH-transgenic zebrafish (Danio rerio) using a DDRT-PCR approach
Authors: Alves-Costa Fernanda A. , Figueiredo Márcio A. , Lanes Carlos F.C. , Almeida Daniela V. , Marins Luis F. , Wasko Adriane P.
Published: May 2012

The presence of higher level of exogenous growth hormone (GH) in transgenic animals could lead to several physiological alterations. A GH transgenic zebrafish (Danio rerio) line was compared to nontransgenic (NT) samples of the species through a DDRT-PCR approach, with the goal of identifying candidate differentially expressed transcripts in brain tissues that could be involved in GH overexpression. Densitometric analyses of two selected amplification products, p300 and ADCY2, pointed to a significant lower gene expression in the transgenic zebrafish (104.02 ± 57.71; 224.10 ± 91.73) when compared to NT samples (249.75 ± 30.08; 342.95 ± 65.19). The present data indicate that p300 and ADCY2 are involved in a regulation system for GH when high circulating levels of this hormone are found in zebrafishes.