Accidental Pinhole and Pinspeck Cameras

We identify and study two types of “accidental” images that can be formed in scenes. The first is an accidental pinhole camera image. The second class of accidental images are “inverse” pinhole camera images, formed by subtracting an image with a small occluder present from a reference image without the occluder. Both types of accidental cameras happen in a variety of different situations. For example, an indoor scene illuminated by natural light, a street with a person walking under the shadow of a building, etc. The images produced by accidental cameras are often mistaken for shadows or interreflections. However, accidental images can reveal information about the scene outside the image, the lighting conditions, or the aperture by which light enters the scene.National Science Foundation (U.S.) (CAREER Award 0747120)United States. Office of Naval Research. Multidisciplinary University Research Initiative (N000141010933)National Science Foundation (U.S.) (CGV 1111415)National Science Foundation (U.S.) (CGV 0964004

Early pneumothorax as a feature of response to crizotinib therapy in a patient with ALK rearranged lung adenocarcinoma.

Background: Single arm phase 1 and 2 studies on Crizotinib in ALK-positive patients so far have shown rapid and durable responses. Spontaneous pneumothoraces as a result of response to anti-cancer therapy are rare in oncology but have been documented in a number of tumour types including lung cancer. This includes cytotoxic chemotherapy as well as molecular targeted agents such as gefitinib and Bevacizumab. These often require chest drain insertion or surgical intervention with associated morbidity and mortality. They have also been associated with response to treatment. This is the first report we are aware of documenting pneumothorax as response to crizotinib therapy.Case presentation: A 48-year-old Caucasian male presented with a Stage IV, TTF1 positive, EGFR wild-type adenocarcinoma of the lung. He received first line chemotherapy with three cycles of cisplatin-pemetrexed chemotherapy with a differential response, and then second-line erlotinib for two months before further radiological evidence of disease progression. Further analysis of his diagnostic specimen identified an ALK rearrangement by fluorescence in situ hybridization (FISH). He was commenced on crizotinib therapy 250 mg orally twice daily. At his 4-week assessment he had a chest radiograph that identified a large left-sided pneumothorax with disease response evident on the right. Chest CT confirmed a 50% left-sided pneumothorax on a background of overall disease response. A chest tube was inserted with complete resolution of the pneumothorax that did not recur following its removal.Conclusion: Our case demonstrates this potential complication of crizotinib therapy and we therefore recommend that pneumothorax be considered in patients on crizotinib presenting with high lung metastatic burden and with worsening dyspnoea. © 2013 Gennatas et al.; licensee BioMed Central Ltd

Clinical Implication of Targeting of Cancer Stem Cells

The existence of cancer stem cells (CSCs) is receiving increasing interest particularly due to its potential ability to enter clinical routine. Rapid advances in the CSC field have provided evidence for the development of more reliable anticancer therapies in the future. CSCs typically only constitute a small fraction of the total tumor burden; however, they harbor self-renewal capacity and appear to be relatively resistant to conventional therapies. Recent therapeutic approaches aim to eliminate or differentiate CSCs or to disrupt the niches in which they reside. Better understanding of the biological characteristics of CSCs as well as improved preclinical and clinical trials targeting CSCs may revolutionize the treatment of many cancers. Copyright (c) 2012 S. Karger AG, Base

RNAseq Analyses Identify Tumor Necrosis Factor-Mediated Inflammation as a Major Abnormality in ALS Spinal Cord

ALS is a rapidly progressive, devastating neurodegenerative illness of adults that produces disabling weakness and spasticity arising from death of lower and upper motor neurons. No meaningful therapies exist to slow ALS progression, and molecular insights into pathogenesis and progression are sorely needed. In that context, we used high-depth, next generation RNA sequencing (RNAseq, Illumina) to define gene network abnormalities in RNA samples depleted of rRNA and isolated from cervical spinal cord sections of 7 ALS and 8 CTL samples. We aligned \u3e50 million 2X150 bp paired-end sequences/sample to the hg19 human genome and applied three different algorithms (Cuffdiff2, DEseq2, EdgeR) for identification of differentially expressed genes (DEG’s). Ingenuity Pathways Analysis (IPA) and Weighted Gene Co-expression Network Analysis (WGCNA) identified inflammatory processes as significantly elevated in our ALS samples, with tumor necrosis factor (TNF) found to be a major pathway regulator (IPA) and TNFα-induced protein 2 (TNFAIP2) as a major network “hub” gene (WGCNA). Using the oPOSSUM algorithm, we analyzed transcription factors (TF) controlling expression of the nine DEG/hub genes in the ALS samples and identified TF’s involved in inflammation (NFkB, REL, NFkB1) and macrophage function (NR1H2::RXRA heterodimer). Transient expression in human iPSC-derived motor neurons of TNFAIP2 (also a DEG identified by all three algorithms) reduced cell viability and induced caspase 3/7 activation. Using high-density RNAseq, multiple algorithms for DEG identification, and an unsupervised gene co-expression network approach, we identified significant elevation of inflammatory processes in ALS spinal cord with TNF as a major regulatory molecule. Overexpression of the DEG TNFAIP2 in human motor neurons, the population most vulnerable to die in ALS, increased cell death and caspase 3/7 activation. We propose that therapies targeted to reduce inflammatory TNFα signaling may be helpful in ALS patients

Mechanisms of Class II correction induced by the crown Herbst appliance as a single-phase Class II therapy : 1 year follow-up

Background The objective of this study is to evaluate the skeletal and dentoalveolar effects of the crown Herbst appliance used alone for a single phase of therapy followed by a 1-year observation period. Methods Forty patients (mean age 13.6 ± 1.3 years) with a stable Class I occlusion 1 year following the treatment with the crown Herbst appliance were selected from a prospective sample of 180 consecutively treated Class II patients. No other appliances were used during treatment or during the follow-up period. The dentoskeletal changes were compared with a matched sample of untreated Class II subjects (mean age 13.9 ± 1.6 years). Lateral cephalograms were taken before treatment, after Herbst treatment (1 year), and after 1-year follow-up. Overcorrection was avoided intentionally. Results Treatment produced an increase in mandibular length, a decrease in ANB angle, and a restriction in the vertical growth of posterior maxilla. The maxillary molars moved backward and tipped distally. The lower incisors proclined markedly, and the upper incisors became retroclined. During the follow-up period, the changes primarily were dentoalveolar in nature, with marked rebound of the upper molars and lower incisors, resulting in some increases in overbite and overjet. Conclusions The occlusal correction of Class II malocclusion observed 1 year after the crown Herbst appliance as a single-phase therapy was achieved primary due to the dentoalveolar changes and only limited skeletal change occurred.publishersversionPeer reviewe

Cue Reactivity in Active Pathological, Abstinent Pathological, and Regular Gamblers

Twenty-one treatment-seeking pathological gamblers, 21 pathological gamblers in recovery, and 21 recreational gamblers watched two video-taped exciting gambling scenarios and an exciting roller-coaster control scenario while their arousal (heart rate and subjective excitement) and urge to gamble were being measured. The gamblers did not differ significantly in cue-elicited heart rate elevations or excitement. However, the active pathological gamblers reported significantly greater urges to gamble across all cues compared to the abstinent pathological gamblers and, with marginal significance (p = 0.06), also compared to the social gamblers. Further exploration of these findings revealed that active pathological gamblers experience urges to gamble in response to exciting situations, whether or not they are gambling related, whereas abstinent and social gamblers only report urges to an exciting gambling-related cue. This suggests that for pathological gamblers excitement itself, irrespective of its source, may become a conditioned stimulus capable of triggering gambling behavior. Implications for treatment and future research are discussed

Systemic Treatments for Mesothelioma: Standard and Novel

Systemic therapy is the only treatment option for the majority of mesothelioma patients, for whom age, co-morbid medical illnesses, non-epithelial histology, and locally advanced disease often preclude surgery. For many years, chemotherapy had a minimal impact on the natural history of this cancer, engendering considerable nihilism. Countless drugs were evaluated, most of which achieved response rates below 20% and median survival of <1 year. Several factors have hampered the evaluation of systemic regimens in patients with mesothelioma. The disease is uncommon, affecting only about 2500 Americans annually. Thus, most clinical trials are small, and randomized studies are challenging to accrue. There is significant heterogeneity within the patient populations of these small trials, for several reasons. Since all of the staging systems for mesothelioma are surgically based, it is almost impossible to accurately determine the stage of a patient who has not been resected. Patients with very early stage disease may be lumped together with far more advanced patients in the same study. The disease itself is heterogenous, with many different prognostic factors, most notably three pathologic subtypes—epithelial, sarcomatoid, and biphasic—that have different natural histories, and varying responses to treatment. Finally, response assessment is problematic, since pleural-based lesions are difficult to measure accurately and reproducibly. Assessment criteria often vary between trials, making some cross-trial comparisons difficult to interpret. Despite these limitations, in recent years, there has been a surge of optimism regarding systemic treatment of this disease. Several cytotoxic agents have been shown to generate reproducible responses, improve quality of life, or prolong survival in mesothelioma. Drugs with single-agent activity include pemetrexed, raltitrexed, vinorelbine, and vinflunine. The addition of pemetrexed or raltitrexed to cisplatin prolongs survival. The addition of cisplatin to pemetrexed, raltitrexed, gemcitabine, irinotecan, or vinorelbine improves response rate. The combination of pemetrexed plus cisplatin is considered the benchmark front-line regimen for this disease, based on a phase III trial in 456 patients that yielded a response rate of 41% and a median survival of 12.1 months. Vitamin supplementation with folic acid is essential to decrease toxicity, though recent data suggests that there may be an optimum dose of folic acid that should be administered; higher doses may diminish the effectiveness of pemetrexed. There are also several unresolved questions about the duration and timing of treatment with pemetrexed that are the subject of planned clinical trials. It is essential to recognize that the improvements observed with the pemetrexed/cisplatin combination, though real, are still modest. Other active drugs or drug combinations may be more appropriate for specific individuals, and further research is still needed to improve upon these results. Since the majority of mesotheliomas in the United States occur in the elderly, non-cisplatin-containing pemetrexed combinations may be more appropriate for some patients. Now that effective agents have been developed for initial treatment, several classical cytotoxic drugs and many novel agents are being evaluated in the second-line setting. These include drugs targeted against the epidermal growth factor, platelet-derived growth factor, vascular endothelial growth factor, src kinase, histone deacetylase, the proteasome, and mesothelin. Given the progress made in recent years, there is reason to believe that more effective treatments will continue to be developed

The role of metacognition in self-critical rumination: an investigation in individuals presenting with low self-esteem

Background: No research, to date, has directly investigated the role of metacognition in self-critical rumination and low self-esteem. Aim: To investigate the presence of metacognitive beliefs about self-critical rumination; the goal of self-critical rumination and its stop signal; and the degree of detachment from intrusive self-critical thoughts. Method: Ten individuals reporting both a self-acknowledged tendency to judge themselves critically and having low self-esteem were assessed using metacognitive profiling, a semi-structured interview. Results: All participants endorsed both positive and negative metacognitive beliefs about self-critical rumination. Positive metacognitive beliefs concerned the usefulness of self-critical rumination as a means of improving cognitive performance and enhancing motivation. Negative metacognitive beliefs concerned the uncontrollability of self-critical rumination and its negative impact on mood, motivation and perception of self-worth. The primary goal of engaging in self-critical rumination was to achieve a better or clearer understanding of a given trigger situation or to feel more motivated to resolve it. However, only four participants were able to identify when this goal had been achieved, which was if the trigger situation were not to occur again. Participants unanimously stated that they were either unable to detach from their self-critical thoughts or could do so some of the time with varying degrees of success. More often than not, though, self-critical thoughts were viewed as facts, would rarely be seen as distorted or biased, and could take hours or days to dissipate. Conclusions: These findings provide preliminary evidence that specific facets of metacognition play a role in the escalation and perseveration of self-critical rumination