Search

The Metacognitions Questionnaire – Short Form (MCQ-30) was designed as a parsimonious measure of the metacognitive beliefs and processes implicated in the maintenance of Generalized Anxiety Disorder (GAD). The present study sought to examine the psychometric properties and clinical utility of the MCQ-30 among people with GAD. One hundred and thirty-nine adults diagnosed with GAD and 76 non-clinical controls completed the MCQ-30 and self-report measures of worry, fear of anxiety, attempted thought suppression, distress, GAD symptoms, and interference. A five-factor structure was evaluated using confirmatory factor analysis (CFA). Among the clinical sample, CFA supported the construct validity of the scale, although the relationship between the factors differed from community samples. Evidence was found for the internal consistency, test-retest reliability, and concurrent, convergent and criterion validity of the MCQ-30 in people with GAD. The treatment sensitivity and clinical responsiveness of the scale were also demonstrated, with the Uncontrollability and Danger Beliefs subscale identified as the most accurate predictor of clinical status. This subscale also exhibited the strongest correlations with most symptom measures, highlighting the cardinal role played by negative beliefs about worry in maintaining clinical levels of GAD. This study provides the first evidence of the reliability, validity and clinical utility of the MCQ-30 with people diagnosed with GAD. [ABSTRACT FROM AUTHOR]

Purpose: Accrual to clinical trials that challenge well-established treatment paradigms represents a unique challenge. Physician opinions on investigation of a novel approach to breast cancer treatment, in which patients with complete response to neoadjuvant chemotherapy are offered omission of lumpectomy, are unknown. NRG-CC006 sought to describe physician attitudes toward a novel approach to breast cancer treatment. Methods: We recruited 18 participants in the fields of surgery, medical oncology, and radiation oncology to participate in the semi-structured telephone interviews. Main outcomes are qualitative themes associated with omission of surgery. Results: Of 18 interview participants, specialty and gender were evenly represented across surgery, medical oncology, and radiation oncology. Qualitative themes included general attitudes toward treatment de-escalation, stakeholder considerations, and trial/protocol considerations. The vast majority of participants expressed interest in investigation of omission of surgery, with all participants endorsing need for further investigation into treatment de-escalation. Stakeholder considerations in opening such a trial emphasized need for multidisciplinary involvement and, particularly, the unique role of surgeons as gatekeepers in breast cancer treatment. Finally, participants endorsed a need for further foundational studies to develop ways to predict complete pathologic response to chemotherapy without surgical intervention. Conclusions: Physicians expressed interest in investigating a novel approach to breast cancer treatment that would omit surgery in complete responders to neoadjuvant chemotherapy. Multidisciplinary input, and specifically surgeon engagement, will be key to the success of future investigations. Ongoing work to develop approaches to predict pathologic complete response accurately is needed to achieve the promise of this idea. ClinTrials #: BR005: NCT03188393 June 13, 2017 [ABSTRACT FROM AUTHOR]

Purpose of Review: Upfront fertility counseling improves quality of life for young breast cancer patients planning for pregnancy post-treatment. We reviewed the literature on the impact, if any, that breast radiation may have on post-treatment fertility and fertility preservation decisions in order to facilitate fertility counseling. Recent Findings: While the ovaries and uterus should not receive significant doses of radiation during breast radiation, negligible radiation doses (that are too low to induce ovarian failure) may result from internal scatter. Despite a low risk of infertility from breast radiation, data suggest that women may have chosen mastectomy to avoid whole-breast radiation due to fertility concerns. Although multiple studies have provided encouraging data with successful pregnancies after breast cancer treatment, the number of patients that underwent breast radiation and required fertility preservation methods are rarely reported. Summary: In conclusion, the impact that breast radiation appears to have on fertility is low and, in our opinion, should not result in patients choosing mastectomy over breast conservation therapy due to fears of infertility. However, further studies specifying the patients receiving breast radiation and requiring fertility preservation methods are warranted to help reassure patients and their providers. [ABSTRACT FROM AUTHOR]

Purpose: A meta-analysis of 22 randomized trials accrued from 1964 to 1986 demonstrated significantly higher rates of locoregional failure (LRF) and breast-cancer mortality in women with 1-3 positive nodes without postmastectomy radiotherapy (PMRT) after mastectomy (mast.). Recent data demonstrate that PMRT reduces distant metastases (DM) in women with pN1 disease. The challenge today is whether all patients with pathologic T1-2pN1 disease have similar substantial LRF/DM risk that routinely warrants PMRT.Methods: We reviewed patients with pT1-2N1 breast cancer treated with mast. ± adjuvant systemic therapy without PMRT from 2000 to 2013. The endpoints were LRF and DM rates, estimated by cumulative incidence method.Results: We identified 468 patients with median follow-up of 6.3 years. Most (71%) were estrogen receptor/progesterone receptor + human epidermal growth factor receptor 2 (HER2). There were 269 patients with 1+ node, 140 patients with 2+ nodes, and 59 patients with 3+ nodes. The 6-year LRF/DM rates were 4.1%/8.4%. Patients with 1+, 2+, and 3+ nodes had 6-year LRF of 2.3, 5.1 and 8.9%, respectively (p = 0.13). The 6-year DM rate was higher in patients with 3+ nodes versus 1-2+ nodes: 15.7% versus 7.4% (p = 0.02). Several subgroups had low 6-year LRF and DM rates, including T1/1+ node (0.8%/4.1% LRF/DM) and micrometastases (0%/5.8% LRF/DM).Conclusions: Patients with pT1-2pN1 represent a heterogeneous group with a wide range of LRF/DM rates. In particular, patients with pT1 tumors and 1 + LN, and patients with micrometastases, had low event rates. These groups would derive small absolute reductions in LRF and DM with addition of PMRT, underscoring the importance of patient selection for PMRT in pT1-2pN1 breast cancer. [ABSTRACT FROM AUTHOR]

The importance of the tumor-associated stroma in cancer progression is clear. However, it remains uncertain whether early events in the stroma are capable of initiating breast tumorigenesis. Here, we show that in the mammary glands of non-tumor bearing mice, stromal-specific phosphatase and tensin homolog (Pten) deletion invokes radiation-induced genomic instability in neighboring epithelium. In these animals, a single dose of whole-body radiation causes focal mammary lobuloalveolar hyperplasia through paracrine epidermal growth factor receptor (EGFR) activation, and EGFR inhibition abrogates these cellular changes. By analyzing human tissue, we discover that stromal PTEN is lost in a subset of normal breast samples obtained from reduction mammoplasty, and is predictive of recurrence in breast cancer patients. Combined, these data indicate that diagnostic or therapeutic chest radiation may predispose patients with decreased stromal PTEN expression to secondary breast cancer, and that prophylactic EGFR inhibition may reduce this risk. [ABSTRACT FROM AUTHOR]

Purpose of Review: The majority of women diagnosed with early-stage breast cancer will undergo radiotherapy. Clinical decisions regarding the delivery of radiotherapy are typically based on clinical and pathologic factors. In contrast, systemic therapy clinical decisions incorporate specific breast cancer biology. This review will focus on how breast cancer biology may help tailor radiotherapy for early-stage patients. Recent Findings: Radiotherapy for early-stage breast cancer is typically delivered for breast conservation. Regional nodal radiotherapy use in early-stage disease is expected to expand in the wake of recent clinical trial publications demonstrating improved disease-free survival in those with one to three axillary nodal metastases. There is a growing body of data demonstrating that intrinsic breast cancer subtypes and luminal multigene assays developed for systemic therapy are also associated with local regional recurrence. Summary: Including tumor biology in addition to standard clinical and pathological factors may lead to a more tailored use of radiotherapy in early-stage breast cancer. [ABSTRACT FROM AUTHOR]

Recent research has extended the metacognitive model of adult psychopathology to childhood anxiety, however the results have been confounded by poor comprehension of the Metacognitions Questionnaire for Children (MCQ-C) amongst 7-8 year olds. The aim of this study was to improve comprehension of the MCQ-C, to enable reliable and valid evaluation of the metacognitive model of anxiety in children. Poorly comprehended items of the MCQ-C were revised to the appropriate reading level and pilot tested with 7-8 year olds. One hundred and eighty seven children aged 7-12 years then completed an online version of the revised MCQ-C (MCQ-CR) and self-report measures of anxiety symptoms, excessive worry and externalising thoughts. The MCQ-CR was well understood by children as young as 7 years and exhibited sound psychometric properties. As predicted, children's negative beliefs about worry, thoughts in general and memories were found to be significantly positively related to symptoms of anxiety disorders. Confirmatory factor analysis supported the construct validity of the scale. Positive beliefs about worry were not associated with children's worry levels, raising questions about the relevance of this element of the metacognitive model with children. Although further validation is required with a clinical sample, these results provide support for the integral role played by metacognitions in childhood anxiety disorders, and suggest that these mechanisms may be appropriate targets for future early intervention and treatment programs. [ABSTRACT FROM AUTHOR]

Over 150,000 cancer patients will be diagnosed with brain metastases this year alone. Survival for those diagnosed with brain metastases remains poor despite multimodality management with surgery, chemotherapy, and radiation. Preventative strategies to mitigate brain metastases have met with mixed results. In leukemia and small cell lung cancer there are defined roles for preventative radiation to be delivered, which can result in improved local control and survival. There is a less defined role for preventative radiation in locally advanced non-small cell lung cancer and budding interest for radiation prevention in breast cancer. The potential impact preventative cranial irradiation may have on neurocognitive function and quality of life needs to be considered prior to its administration. [ABSTRACT FROM AUTHOR]

Randomized clinical trials and meta-analyses have clearly demonstrated that radiation after definitive surgery can improve local-regional control and consequently breast cancer survival. There has been some controversy, however, regarding when and in which patient populations more extensive radiation to the nodal regions is warranted. This review focuses on the current evidence supporting the use of radiation and the rationale for determining patients who will derive the most benefit. [ABSTRACT FROM AUTHOR]

Interaction of pathogens with cells of the immune system results in activation of inflammatory gene expression. This response, although vital for immune defence, is frequently deleterious to the host due to the exaggerated production of inflammatory proteins. The scope of inflammatory responses reflects the activation state of signalling proteins upstream of inflammatory genes as well as signal-induced assembly of nuclear chromatin complexes that support mRNA expression. Recognition of post-translationally modified histones by nuclear proteins that initiate mRNA transcription and support mRNA elongation is a critical step in the regulation of gene expression. Here we present a novel pharmacological approach that targets inflammatory gene expression by interfering with the recognition of acetylated histones by the bromodomain and extra terminal domain (BET) family of proteins. We describe a synthetic compound (I-BET) that by 'mimicking' acetylated histones disrupts chromatin complexes responsible for the expression of key inflammatory genes in activated macrophages, and confers protection against lipopolysaccharide-induced endotoxic shock and bacteria-induced sepsis. Our findings suggest that synthetic compounds specifically targeting proteins that recognize post-translationally modified histones can serve as a new generation of immunomodulatory drugs. [ABSTRACT FROM AUTHOR]

Imaging and local therapy are important modalities for detection and management of localized breast cancer. Improvements in screening and local therapy have contributed to reduced breast cancer-associated morbidity and mortality. The Coalition of Cancer Cooperative Groups (CCCG) convened the Scientific Leadership Council (SLC) in breast cancer, an expert panel, to identify priorities for future research and current trials with greatest practice-changing potential. Panelists formed a consensus on research priorities for breast imaging and locoregional therapy, and also identified six trials judged to be of high priority. Current high priority trials included trials determining: (1) the role of accelerated partial breast versus whole-breast radiation (B39), (2) the feasibility, safety, and local and systemic control of small localized breast cancers treated with tumor ablation (Z1072), (3) the role of removal of the primary cancer in selected patients with metastatic disease (E2108), and (4) the clinical and biological effects of pre-operative anti-HER2-directed and ER-directed therapies in localized or locally advanced breast cancer (B41, Z1031, Z1041). Ongoing and future trials will further refine optimal locoregional management, and additional research is required to develop improved screening methods and identify high risk populations most likely to benefit from targeted screening. [ABSTRACT FROM AUTHOR]

Background: End tidal carbon dioxide (ETCO(2)) in non-intubated patients can be monitored using either sidestream or flow-through capnometry [Yamamori et al., J Clin Monit Comput 22(3):209-220, 2008]. The hypothesis of this validation study is that, flow-through capnometry will yield a more accurate estimate of ETCO(2) than sidestream capnometry when evaluated in a bench study during low tidal volumes and high oxygen administration via nasal cannula. Secondarily, when ETCO(2) from each is compared to arterial CO(2) (PaCO(2)) during a study in which healthy, non-intubated volunteers are tested under normocapnic, hypocapnic and hypercapnic conditions, the flow-through capnometer will resemble PaCO(2) more closely than the sidestream capnometer. This will be especially true during periods of lower minute ventilation and high oxygen flow rates via mask in non-intubated, remifentanil sedated, healthy volunteers whose physiologic deadspace is small.Methods: The performance of a flow-through (cap-ONE, Nihon Kohden, Tokyo, Japan) and a sidestream (Microcap Smart CapnoLine Plus, Oridion Inc., Needham, MA) capnometer were compared in a bench study and a volunteer trial. A bench study evaluated ETCO(2) accuracy using waveforms generated via mechanical lungs during low tidal volumes and high oxygen flow rates. A volunteer study compared the ETCO(2) for each capnometer against PaCO(2) during sedation in which 8 l O(2) was delivered via mask rather than the nasal cannula.Results: In the bench study, the flow-through capnometer gave slightly higher values of ETCO(2) during high-flow oxygen and no discernable differences during variable tidal volumes. Bland and Altman plots comparing ETCO(2) to PaCO(2) showed essentially equal performance between the two capnometers in the volunteers.Conclusions: Within a wide limit of agreement between the volunteer and bench study, flow-through and sidestream capnometry performed equally well during bench testing and in non-intubated, sedated patients. [ABSTRACT FROM AUTHOR]

The article presents abstracts of cancer research. They include "Continuing Medical Education Homogenizes Surveillance Strategies for Rectal Cancer Patients after Initial Treatment," "Transliteration of the Center for Epidemiological Studies: Depression Scale for American Sign Language Users" and "The Role of Community Health Workers in Academic Research."

The vertebrate olfactory receptor (OR) subgenome harbors the largest known gene family, which has been expanded by the need to provide recognition capacity for millions of potential odorants. We implemented an automated procedure to identify all OR coding regions from published sequences. This led us to the identification of 831 OR coding regions (including pseudogenes) from 24 vertebrate species. The resulting dataset was subjected to neighbor-joining phylogenetic analysis and classified into 32 distinct families, 14 of which include only genes from tetrapodan species (Class II ORs). We also report here the first identification of OR sequences from a marsupial (koala) and a monotreme (platypus). Analysis of these OR sequences suggests that the ancestral mammal had a small OR repertoire, which expanded independently in all three mammalian subclasses. Classification of ``fish-like'' (Class I) ORs indicates that some of these ancient ORs were maintained and even expanded in mammals. A nomenclature system for the OR gene superfamily is proposed, based on a divergence evolutionary model. The nomenclature consists of the root symbol `OR', followed by a family numeral, subfamily letter(s), and a numeral representing the individual gene within the subfamily. For example, OR3A1 is an OR gene of family 3, subfamily A, and OR7E12P is an OR pseudogene of family 7, subfamily E. The symbol is to be preceded by a species indicator. We have assigned the proposed nomenclature symbols for all 330 human OR genes in the database. A WWW tool for automated name assignment is provided. [ABSTRACT FROM AUTHOR]

Reports the cloning of a complementary DNA encoding a subtype of the gamma-aminobutyric acid B (GABAB) receptor (GABABR2), which was identified by mining expressed-sequence-tag databases. The indication that, in vivo, functional brain GABAB receptors may be heterodimers composed of GABABR1 and GABABR2; GABA being the main inhibitory neurotransmitter in the mammalian central nervous system.

Reports on the identification of three cellular proteins that bind to the adenovirus E1B 19K proteins. Ability of E1B 19K to inhibit apoptosis; Use of the yeast two-hybrid system to identify the binding proteins; Effect of the overexpression of the bak protein.

Presents several reports provided by the American Association for Cancer Education (AACE) Section Chairs from the individual Section meetings at the 38th Annual Meeting of the AACE in Baltimore, Maryland from October 14 to 17, 2004. Discussion on ways members can improve their approach to the evaluation of cancer education programs; Proposed ideas on how they can apply their knowledge in cancer prevention; Purpose of the R25E grants stimulated from AACE activities.

Addresses concerns raised by Newton Morton in the November 1998 issue of 'Nature Genetics,' regarding gene nomenclature. Effects of problems in nomenclature on map integration in human genetics; Arguments against proposals to sort out nomenclature in one species before any cross-species collaboration.