Age Differences in Intra-Individual Variability in Simple and Choice Reaction Time: Systematic Review and Meta-Analysis

Intra-individual variability in reaction time (RT IIV) is considered to be an index of central nervous system functioning. Such variability is elevated in neurodegenerative diseases or following traumatic brain injury. It has also been suggested to increase with age in healthy ageing.To investigate and quantify age differences in RT IIV in healthy ageing; to examine the effect of different tasks and procedures; to compare raw and mean-adjusted measures of RT IIV.Four electronic databases: PsycINFO, Medline, Web of Science and EMBASE, and hand searching of reference lists of relevant studies.English language journal articles, books or book chapters, containing quantitative empirical data on simple and/or choice RT IIV. Samples had to include younger (under 60 years) and older (60 years and above) human adults.Studies were evaluated in terms of sample representativeness and data treatment. Relevant data were extracted, using a specially-designed form, from the published report or obtained directly from the study authors. Age-group differences in raw and RT-mean-adjusted measures of simple and choice RT IIV were quantified using random effects meta-analyses.Older adults (60+ years) had greater RT IIV than younger (20-39) and middle-aged (40-59) adults. Age effects were larger in choice RT tasks than in simple RT tasks. For all measures of RT IIV, effect sizes were larger for the comparisons between older and younger adults than between older and middle-aged adults, indicating that the age-related increases in RT IIV are not limited to old age. Effect sizes were also larger for raw than for RT-mean-adjusted RT IIV measures.RT IIV is greater among older adults. Some (but not all) of the age-related increases in RT IIV are accounted for by the increased RT means

Laryngeal Preservation Strategies in Locally Advanced Laryngeal and Hypopharyngeal Cancers.

For long, the treatment of locoregionally advanced laryngeal and hypopharyngeal squamous cell cancers (SCC) consisted of either total laryngectomy (TL) or definitive radiotherapy (RT). The development of induction cisplatin plus 5-fluorouracil (PF) and the correlation between chemosensitivity and radiosensitivity in previously untreated patients opened a new era of treatment aiming at laryngeal preservation (LP). The fundamental concept was to employ induction PF in order to select patients for subsequent treatment with either TL or RT according to tumor response to PF. The first two trials (VALGSG for laryngeal SCC and EORTC 24891 for hypopharyngeal SCC) concluded that such an approach could preserve nearly 60% of larynx without deleterious impact on survival. The EORTC 24954 trial compared 4 cycles of induction PF followed by RT in good responders vs. alternating PF-RT in laryngeal and hypopharyngeal SCC. There was no significant difference in 5-year overall survival with a functional larynx between the two arms (31 vs. 35%). The GORTEC 2000-01 trial compared induction PF to induction PF plus docetaxel (TPF) both followed by RT in good responders in larynx and hypopharynx SCC. The 5-year LP was significantly higher in the TPF arm (60 vs. 39%) but without a difference in survival. The RTOG 91-11 trial compared induction PF followed by RT in good responders vs. concurrent chemoradiotherapy (chemo-RT) vs. RT alone in laryngeal SCC. There was no significant difference in 5-year laryngectomy-free survival between the patients treated with induction chemotherapy (44%) vs. those treated with chemo-RT (47%), both being superior to RT alone (34%). At 5 years, LP was superior with chemo-RT: 84 vs. 71% with induction PF. Two phase II trials explored the role of cetuximab (E) in LP in laryngeal and hypopharyngeal SCC. The TREMPLIN trial compared RT+E or chemo-RT (RT + P) after TPF. The DeLOS-II trial compared TPE followed by RT+E vs. TP followed by RT. However, these trials failed to indicate an advantage for the incorporation of E in the treatment paradigm. To date, two approaches for LP have been validated: induction TPF followed by RT for laryngeal and hypopharyngeal SCC and concurrent chemo-RT for laryngeal SCC. An ongoing trial (SALTORL) is comparing these two approaches, induction TPF and chemo-RT, in laryngeal/ hypopharyngeal SCC

Formal and efficient verification techniques for Real-Time UML models

The real-time UML profile TURTLE has a formal semantics expressed by translation into a timed process algebra: RT-LOTOS. RTL, the formal verification tool developed for RT-LOTOS, was first used to check TURTLE models against design errors. This paper opens new avenues for TURTLE model verification. It shows how recent work on translating RT-LOTOS specifications into Time Petri net model may be applied to TURTLE. RT-LOTOS to TPN translation patterns are presented. Their formal proof is the subject of another paper. These patterns have been implemented in a RT-LOTOS to TPN translator which has been interfaced with TINA, a Time Petri Net Analyzer which implements several reachability analysis procedures depending on the class of property to be verified. The paper illustrates the benefits of the TURTLE->RT-LOTOS->TPN transformation chain on an avionic case study

The effect of distance on reaction time in aiming movements

Target distance affects movement duration in aiming tasks but its effect on reaction time (RT) is poorly documented. RT is a function of both preparation and initiation. Experiment 1 pre-cued movement (allowing advanced preparation) and found no influence of distance on RT. Thus, target distance does not affect initiation time. Experiment 2 removed pre-cue information and found that preparing a movement of increased distance lengthens RT. Experiment 3 explored movements to targets of cued size at non-cued distances and found size altered peak speed and movement duration but RT was influenced by distance alone. Thus, amplitude influences preparation time (for reasons other than altered duration) but not initiation time. We hypothesise that the RT distance effect might be due to the increased number of possible trajectories associated with further targets: a hypothesis that can be tested in future experiments

Thyroxine is the serum factor that regulates morphogenesis of columnar cartilage from isolated chondrocytes in chemically defined medium.

Epiphyseal chondrocytes cultured in a medium containing 10% serum may be maintained as three dimensional aggregates and differentiate terminally into hypertrophic cells. There is an attendant expression of genes encoding type X collagen and high levels of alkaline phosphatase activity. Manipulation of the serum concentration to optimal levels of 0.1 or 0.01% in this chondrocyte pellet culture system results in formation of features of developing cartilage architecture which have been observed exclusively in growth cartilage in vivo. Cells are arranged in columns radiating out from the center of the tissue, and can be divided into distinct zones corresponding to the recognized stages of chondrocyte differentiation. Elimination of the optimal serum concentration in a chemically defined medium containing insulin eliminates the events of terminal differentiation of defined cartilage architecture. Chondrocytes continue to enlarge into hypertrophic cells and synthesize type X collagen mRNA and protein, but in the absence of the optimal serum concentration, alkaline phosphatase activity does not increase and the cells retain a random orientation. Addition of thyroxine to the chemically defined medium containing insulin and growth hormone results in dose-dependent increases in both type X collagen synthesis and alkaline phosphatase activity, and reproduces the optimal serum-induced morphogenesis of chondrocytes into a columnar pattern. These experiments demonstrate the critical role of thyroxine in cartilage morphogenesis

Enhancement of radiosensitivity by the novel anticancer quinolone derivative vosaroxin in preclinical glioblastoma models

Purpose: Glioblastoma multiforme (GBM) is the most aggressive brain tumor. The activity of vosaroxin, a first-in-class anticancer quinolone derivative that intercalates DNA and inhibits topoisomerase II, was investigated in GBM preclinical models as a single agent and combined with radiotherapy (RT). Results: Vosaroxin showed antitumor activity in clonogenic survival assays, with IC50 of 10-100 nM, and demonstrated radiosensitization. Combined treatments exhibited significantly higher γH2Ax levels compared with controls. In xenograft models, vosaroxin reduced tumor growth and showed enhanced activity with RT; vosaroxin/RT combined was more effective than temozolomide/RT. Vosaroxin/ RT triggered rapid and massive cell death with characteristics of necrosis. A minor proportion of treated cells underwent caspase-dependent apoptosis, in agreement with in vitro results. Vosaroxin/RT inhibited RT-induced autophagy, increasing necrosis. This was associated with increased recruitment of granulocytes, monocytes, and undifferentiated bone marrow-derived lymphoid cells. Pharmacokinetic analyses revealed adequate blood-brain penetration of vosaroxin. Vosaroxin/RT increased disease-free survival (DFS) and overall survival (OS) significantly compared with RT, vosaroxin alone, temozolomide, and temozolomide/RT in the U251-luciferase orthotopic model. Materials and Methods: Cellular, molecular, and antiproliferative effects of vosaroxin alone or combined with RT were evaluated in 13 GBM cell lines. Tumor growth delay was determined in U87MG, U251, and T98G xenograft mouse models. (DFS) and (OS) were assessed in orthotopic intrabrain models using luciferasetransfected U251 cells by bioluminescence and magnetic resonance imaging. Conclusions: Vosaroxin demonstrated significant activity in vitro and in vivo in GBM models, and showed additive/synergistic activity when combined with RT in O6- methylguanine methyltransferase-negative and -positive cell lines

Locally Advanced Spiroadenocarcinoma in the Regional Axilla of a Breast Cancer Patient: Hallmarks of Definitive Diagnosis and Management.

Eccrine spiroadenocarcinoma is an extremely rare malignant eccrine gland tumor which may masquerade as other more common malignancies such as poorly differentiated squamous carcinoma or metastatic breast cancer. We report a case of an ulcerated axillary skin lesion with bulky adenopathy in a 77 year-old female with a prior history of ipsilateral triple negative breast carcinoma. The clear transition of benign spiradenoma to malignant carcinoma was essential to establishing a definitive diagnosis and treatment plan