On the behaviour of lung tissue under tension and compression

Lung injuries are common among those who suffer an impact or trauma. The relative severity of injuries up to physical tearing of tissue have been documented in clinical studies. However, the specific details of energy required to cause visible damage to the lung parenchyma are lacking. Furthermore, the limitations of lung tissue under simple mechanical loading are also not well documented. This study aimed to collect mechanical test data from freshly excised lung, obtained from both Sprague-Dawley rats and New Zealand White rabbits. Compression and tension tests were conducted at three different strain rates: 0.25, 2.5 and 25 min−1. This study aimed to characterise the quasi-static behaviour of the bulk tissue prior to extending to higher rates. A nonlinear viscoelastic analytical model was applied to the data to describe their behaviour. Results exhibited asymmetry in terms of differences between tension and compression. The rabbit tissue also appeared to exhibit stronger viscous behaviour than the rat tissue. As a narrow strain rate band is explored here, no conclusions are being drawn currently regarding the rate sensitivity of rat tissue. However, this study does highlight both the clear differences between the two tissue types and the important role that composition and microstructure can play in mechanical response

Discerning Tumor Status from Unstructured MRI Reports—Completeness of Information in Existing Reports and Utility of Automated Natural Language Processing

Information in electronic medical records is often in an unstructured free-text format. This format presents challenges for expedient data retrieval and may fail to convey important findings. Natural language processing (NLP) is an emerging technique for rapid and efficient clinical data retrieval. While proven in disease detection, the utility of NLP in discerning disease progression from free-text reports is untested. We aimed to (1) assess whether unstructured radiology reports contained sufficient information for tumor status classification; (2) develop an NLP-based data extraction tool to determine tumor status from unstructured reports; and (3) compare NLP and human tumor status classification outcomes. Consecutive follow-up brain tumor magnetic resonance imaging reports (2000–­2007) from a tertiary center were manually annotated using consensus guidelines on tumor status. Reports were randomized to NLP training (70%) or testing (30%) groups. The NLP tool utilized a support vector machines model with statistical and rule-based outcomes. Most reports had sufficient information for tumor status classification, although 0.8% did not describe status despite reference to prior examinations. Tumor size was unreported in 68.7% of documents, while 50.3% lacked data on change magnitude when there was detectable progression or regression. Using retrospective human classification as the gold standard, NLP achieved 80.6% sensitivity and 91.6% specificity for tumor status determination (mean positive predictive value, 82.4%; negative predictive value, 92.0%). In conclusion, most reports contained sufficient information for tumor status determination, though variable features were used to describe status. NLP demonstrated good accuracy for tumor status classification and may have novel application for automated disease status classification from electronic databases

Temozolomide 3 weeks on and 1 week off as first-line therapy for recurrent glioblastoma: phase II study from gruppo italiano cooperativo di neuro-oncologia (GICNO)

The efficacy of temozolomide strongly depends on O6-alkylguanine DNA-alkyl transferase (AGAT), which repairs DNA damage caused by the drug itself. Low-dose protracted temozolomide administration can decrease AGAT activity. The main end point of the present study was therefore to test progression-free survival at 6 months (PFS-6) in glioblastoma patients following a prolonged temozolomide schedule. Chemonaïve glioblastoma patients with disease recurrence or progression after surgery and standard radiotherapy were considered eligible. Chemotherapy cycles consisted of temozolomide 75 mg/m2/daily for 21 days every 28 days until disease progression. O6-methyl-guanine-DNA-methyl-tranferase (MGMT) was determined in 22 patients (66.7%). A total of 33 patients (median age 57 years, range 31–71) with a median KPS of 90 (range 60–100) were accrued. The overall response rate was 9%, and PFS-6 30.3% (95% CI:18–51%). No correlation was found between the MGMT promoter methylation status of the tumours and the overall response rate, time to progression and survival. In 153 treatment cycles delivered, the most common grade 3/4 event was lymphopoenia. The prolonged temozolomide schedule considered in the present study is followed by a high PFS-6 rate; toxicity is acceptable. Further randomised trials should therefore be conducted to confirm the efficacy of this regimen

Phase I dose-escalation and pharmacokinetic study of temozolomide (SCH 52365) for refractory or relapsing malignancies

Temozolomide, an oral cytotoxic agent with approximately 100% bioavailability after one administration, has demonstrated schedule-dependent clinical activity against highly resistant cancers. Thirty patients with minimal prior chemotherapy were enrolled in this phase I trial to characterize the drug's safety, pharmacokinetics and anti-tumour activity, as well as to assess how food affects oral bioavailability. To determine dose-limiting toxicities (DLT) and the maximum tolerated dose (MTD), temozolomide 100–250 mg m−2 was administered once daily for 5 days every 28 days. The DLT was thrombocytopenia, and the MTD was 200 mg m−2 day−1. Subsequently, patients received the MTD to study how food affects the oral bioavailability of temozolomide. When given orally once daily for 5 days, temozolomide was well tolerated and produced a non-cumulative, transient myelosuppression. The most common non-haematological toxicities were mild to moderate nausea and vomiting. Clinical activity was observed against several advanced cancers, including malignant glioma and metastatic melanoma. Temozolomide demonstrated linear and reproducible pharmacokinetics and was rapidly absorbed (mean Tmax ~1 h) and eliminated (mean t1/2 = 1.8 h). Food produced a slight reduction (9%) in absorption of temozolomide. Temozolomide 200 mg m−2 day−1 for 5 days, every 28 days, is recommended for phase II studies. © 1999 Cancer Research Campaig

Effects of Endolithic Parasitism on Invasive and Indigenous Mussels in a Variable Physical Environment

Biotic stress may operate in concert with physical environmental conditions to limit or facilitate invasion processes while altering competitive interactions between invaders and native species. Here, we examine how endolithic parasitism of an invasive and an indigenous mussel species acts in synergy with abiotic conditions of the habitat. Our results show that the invasive Mytilus galloprovincialis is more infested than the native Perna perna and this difference is probably due to the greater thickness of the protective outer-layer of the shell of the indigenous species. Higher abrasion due to waves on the open coast could account for dissimilarities in degree of infestation between bays and the more wave-exposed open coast. Also micro-scale variations of light affected the level of endolithic parasitism, which was more intense at non-shaded sites. The higher levels of endolithic parasitism in Mytilus mirrored greater mortality rates attributed to parasitism in this species. Condition index, attachment strength and shell strength of both species were negatively affected by the parasites suggesting an energy trade-off between the need to repair the damaged shell and the other physiological parameters. We suggest that, because it has a lower attachment strength and a thinner shell, the invasiveness of M. galloprovincialis will be limited at sun and wave exposed locations where endolithic activity, shell scouring and risk of dislodgement are high. These results underline the crucial role of physical environment in regulating biotic stress, and how these physical-biological interactions may explain site-to-site variability of competitive balances between invasive and indigenous species

Efflux in Fungi: La Pièce de Résistance

Pathogens must be able to overcome both host defenses and antimicrobial treatment in order to successfully infect and maintain colonization of the host. One way fungi accomplish this feat and overcome intercellular toxin accumulation is efflux pumps, in particular ATP-binding cassette transporters and transporters of the major facilitator superfamily. Members of these two superfamilies remove many toxic compounds by coupling transport with ATP hydrolysis or a proton gradient, respectively. Fungal genomes encode a plethora of members of these families of transporters compared to other organisms. In this review we discuss the role these two fungal superfamilies of transporters play in virulence and resistance to antifungal agents. These efflux transporters are responsible not only for export of compounds involved in pathogenesis such as secondary metabolites, but also export of host-derived antimicrobial compounds. In addition, we examine the current knowledge of these transporters in resistance of pathogens to clinically relevant antifungal agents

Prevalence of anaemia in older persons: systematic review

<p>Abstract</p> <p>Background</p> <p>Ageing populations will impact on healthcare provision, especially since extra years are not necessarily spent in good health. It is important to identify and understand the significance of common medical problems in older people. Anaemia may be one such problem. We report on the prevalence of anaemia in cohorts of elderly people in the general population. The presence of anaemia is associated with a worse prognosis for both morbidity and mortality.</p> <p>Methods</p> <p>Electronic searching and reference lists of published reports were used to identify studies that reported on prevalence of anaemia in cohorts of at least 100 individuals predominantly aged 65 years and over living in developed countries, together with criteria used to define anaemia. Studies of anaemia prevalence in specific disease groups or published before 1980 were excluded. Prevalence data for the entire cohort, for men and women separately and for different age bands were extracted.</p> <p>Results</p> <p>Forty-five studies contributed data. Thirty-four studies (n = 85,409) used WHO criteria to define anaemia. The weighted mean prevalence was 17% (3–50%) overall, and 12% (3–25%) in studies based in the community (27, n = 69,975), 47% (31–50%) in nursing homes (3, n = 1481), and 40% (40–72%) in hospital admissions (4, n = 13,953). Anaemia prevalence increased with age, was slightly higher in men than women, and was higher in black people than white. Most individuals classified as anaemic using WHO criteria were only mildly anaemic.</p> <p>Conclusion</p> <p>Anaemia, as defined by WHO criteria, is common in older people living in the community and particularly common in nursing home residents and hospital admissions. Predicted demographic changes underline the need to understand more about anaemia in older people.</p