Tyrosine kinase signalling in breast cancer: ErbB family receptor tyrosine kinases

ERBB family receptor tyrosine kinases are overexpressed in a significant subset of breast cancers. One of these receptors, HER2/neu, or ErbB-2, is the target for a new rational therapeutic antibody, Herceptin. Other inhibitors that target this receptor, and another family member, the epidermal growth factor (EGF) receptor, are moving into clinical trials. Both of these receptors are sometimes overexpressed in breast cancer, and still subject to regulation by hormones and other physiological regulators. Optimal use of therapeutics targeting these receptors will require consideration of the several modes of regulation of these receptors and their interactions with steroid receptors

A protocol for developing reporting guidelines for laboratory studies in Endodontology

Laboratory‐based research studies are the most common form of research endeavour and make up the majority of manuscripts that are submitted for publication in the field of Endodontology. The scientific information derived from laboratory studies can be used to design a wide range of subsequent studies and clinical trials and may have translational potential to benefit clinical practice. Unfortunately, the majority of laboratory‐based articles submitted for publication fail the peer‐review step, because unacceptable flaws or substantial limitations are identified. Even when apparently well‐conducted laboratory‐based articles are peer‐reviewed, they can often require substantial corrections prior to the publication. It is apparent that some authors and reviewers may lack the training and experience to have developed a systematic approach to evaluate the quality of laboratory studies. Occasionally, even accepted manuscripts contain limitations that may compromise interpretation of data. To help authors avoid manuscript rejection and correction pitfalls, and to aid editors/reviewers to evaluate manuscripts systematically, the purpose of this project is to establish and publish quality guidelines for authors to report laboratory studies in the field of Endodontology so that the highest standards are achieved. The new guidelines will be named–‘Preferred Reporting Items for Laboratory studies in Endodontology’ (PRILE). A steering committee was assembled by the project leads to develop the guidelines through a five‐phase consensus process. The committee will identify new items as well as review and adapt items from existing guidelines. The items forming the draft guidelines will be reviewed and refined by a PRILE Delphi Group (PDG). The items will be evaluated by the PDG on a nine‐point Likert scale for relevance and inclusion. The agreed items will then be discussed by a PRILE face‐to‐face consensus meeting group (PFCMG) formed by 20 individuals to further refine the guidelines. This will be subject to final approval by the steering committee. The approved PRILE guidelines will be disseminated through publication in relevant journals, presented at congresses/meetings, and be freely available on a dedicated website. Feedback and comments will be solicited from researchers, editors and peer reviewers, who are invited to contact the steering committee with comments to help them update the guidelines periodically

Disentangling regional and local tree diversity in the Amazon

This is the author accepted manuscript. The final version is available from Wiley via the DOI in this recordWe analyzed the most extensive data set of tree inventory plots spread over the complete Amazon basin and Guiana shield. We aimed to separate the regional and local tree alpha‐diversity to investigate the drivers of diversity at the relevant scale. Our results are consistent with the partitioning of total tree alpha‐diversity into regional and local components, which are controlled by evolutionary‐ and ecological processes, respectively. Regional diversity is correlated with palaeo‐climatic stability (31%), and long‐term large‐scale ecosystem dynamics (14%), as represented by the age of the geological formation. Both mechanisms contribute to high diversity in the central to western Amazon. Actual rainfall seasonality is correlated with regional tree diversity to a certain extent (19%), but we argue that this is of little consequence for the evolutionary drivers of the regional species pool. Frequency of disturbance is the main process driving local diversity, although its explanatory power is relatively small (17%).The first author was supported by PAN‐AMAZONIA project, Inst. Internacional de Educação do Brasil (BECA program) and Conselho Nacional de Ciência e Tecnologia (CNPq – Brazil)

The long-term follow-up of patients with a congenital diaphragmatic hernia: a broad spectrum of morbidity

Congenital diaphragmatic hernia (CDH) is a life-threatening anomaly with a mortality rate of approximately 40-50%, depending on case selection. It has been suggested that new therapeutic modalities such as nitric oxide (NO), high frequency oxygenation (HFO) and extracorporal membrane oxygenation (ECMO) might decrease mortality associated with pulmonary hypertension and the sequelae of artificial ventilation. When these new therapies indeed prove to be beneficial, a larger number of children with severe forms of CDH might survive, resulting in an increase of CDH-associated complications and/or consequences. In follow-up studies of infants born with CDH, many complications including pulmonary damage, cardiovascular disease, gastro-intestinal disease, failure to thrive, neurocognitive defects and musculoskeletal abnormalities have been described. Long-term pulmonary morbidity in CDH consists of obstructive and restrictive lung function impairments due to altered lung structure and prolonged ventilatory support. CDH has also been associated with persistent pulmonary vascular abnormalities, resulting in pulmonary hypertension in the neonatal period. Long-term consequences of pulmonary hypertension are unknown. Gastro-esophageal reflux disease (GERD) is also an important contributor to overall morbidity, although the underlying mechanism has not been fully understood yet. In adult CDH survivors incidence of esophagitis is high and even Barrett's esophagus may ensue. Yet, in many CDH patients a clinical history compatible with GERD seems to be lacking, which may result in missing patients with pathologic reflux disease. Prolonged unrecognized GERD may eventually result in failure to thrive. This has been found in many young CDH patients, which may also be caused by insufficient intake due to oral aversion and increased caloric requirements due to pulmonary morbidity. Neurological outcome is determined by an increased risk of perinatal and neonatal hypoxemia in the first days of life of CDH patients. In patients treated with ECMO, the incidence of neurological deficits is even higher, probably reflecting more severe hypoxemia and the risk of ECMO associated complications. Many studies have addressed the substantial impact of the health problems described above, on the overall well-being of CDH patients, but most of them concentrate on the first years after repair and only a few studies focus on the health-related quality of life in CDH patients. Considering the scattered data indicating substantial morbidity in long-term survivors of CDH, follow-up studies that systematically assess long-term sequelae are mandatory. Based on such studies a more focused approach for routine follow-up programs may be establishe