N2 N3 Research Articles

Effects of respiratory muscle therapy on obstructive sleep apnea: a systematic review and meta-analysis

The purpose of this study is to conduct a systematic review and meta-analysis evaluating the effects of respiratory muscle therapy (ie, oropharyngeal exercises, speech therapy, breathing exercises, wind musical instruments) compared with control therapy or no treatment in improving apnea-hypopnea index ([AHI] primary outcome), sleepiness, and other polysomnographic outcomes for patients diagnosed with obstructive sleep apnea (OSA). Only randomized controlled trials with a placebo therapy or no treatment searched using PubMed, EMBASE, Cochrane, and Web of Science up to November 2018 were included, and assessment of risk of bias was completed using the Cochrane Handbook. Nine studies with 394 adults and children diagnosed with mild to severe OSA were included, all assessed at high risk of bias. Eight of the 9 studies measured AHI and showed a weighted average overall AHI improvement of 39.5% versus baselines after respiratory muscle therapy. Based on our meta-analyses in adult studies, respiratory muscle therapy yielded an improvement in AHI of -7.6 events/h (95% confidence interval [CI] = -11.7 to -3.5; P ≤ .001), apnea index of -4.2 events/h (95% CI = -7.7 to -0.8; P ≤ .016), Epworth Sleepiness Scale of -2.5 of 24 (95% CI= -5.1 to -0.1; P ≤ .066), Pittsburgh Sleep Quality Index of -1.3 of 21 (95% CI= -2.4 to -0.2; P ≤ .026), snoring frequency (P = .044) in intervention groups compared with controls. This systematic review highlights respiratory muscle therapy as an adjunct management for OSA but further studies are needed due to limitations including the nature and small number of studies, heterogeneity of the interventions, and high risk of bias with low quality of evidence.

The impact of returning to a daytime schedule on sleep, performance and mood after simulated fixed and rotating split shift schedules

Split shift schedules may be a suitable alternative to long shifts due to reduced accumulation of sleep pressure. However, returning to a daytime schedule (RTDS), performance and sleep deficits may occur as a result of changing the timing of sleep and wake periods. The current study investigated sleep, performance and mood during and following four 24h periods on fixed and rotating split shift schedules. Twenty four participants (10M, 21-36y) completed a 9-day laboratory study with two 10h baseline sleeps (22:00h-08:00h); one of three shift conditions: one of two 6h on / 6h off schedules, (Fixed A: 5h-time in bed (TIB) at 03:00h/15:00h, or Fixed B: 5h TIB at 09:00h/21:00h), or an 8h on / 8h off schedule (Rotating: 6h40 TIB); and RTDS with 10h TIB for 2-nights (22:00h-08:00h). The Fixed B condition had significantly less N3 sleep during RTDS compared to baseline (p<0.01). For all conditions, sleep onset latency, N2 onset latency and N3 onset latency were significantly longer during RTDS compared to baseline (p<0.05). Psychomotor vigilance was stable throughout the study. Subjective sleepiness (p<0.001) and positive affect (p<0.01) worsened during the shift schedule period but returned to baseline levels during RTDS. Negative affect increased during the shift schedule period and did not return to baseline levels upon RTDS (p<0.001). Although differences in sleep and negative affect were observed upon RTDS, the fixed and rotating shift schedules did not substantially worsen performance during the shift schedule or after RTDS in controlled laboratory conditions that are ideal for sleep.

A retrospective study of the effect of neoadjuvant chemotherapy as a primary treatment of advanced breast cancer and its effect on surgical modalities.

Aim of the work: neoadjuvant chemotherapy in downstaging of each the primary tumour and axillary disease, reach pathological complete response to neo-adjuvant remedy have had a marked effect on loco-regional remedy concerns, boom opportunities facilitating surgical intervention compare its impact on surgical management of breast cancers either mastectomy or BCS. Patients and Method: This retrospective study is carried out on one hundred female patients with documented breast cancer, examined in the medical oncology department & nuclear medicine remedy Sohag university hospitals and sohag cancers institute, at the period from (2013 - 2018). Results: Number of patients identified before receiving neo-adjuvant chemotherapy asT2 become 15 instances (15%),32 cases (32%) become T3,24 cases(24%) was T4a, 24 instances (24%) T4b,3 instances (three%) changed into T4c and 2cases (2% ) became T4d. The number of instances identified before receiving neo-adjuvant chemotherapy as N0 was4 cases (4%), N1 turned into 37 instances (37%), N2 became fifty-two instances (fifty-two %) and N3 turned into (7%). Number of cases that identified postoperative T0 was 10 cases(10%),T1 turned into 10 instances(10%),T2 was 47 instances(forty seven%),T3 was21 cases (21%),T4a turned into 5cases (5%) and T4b turned into 7 instances (7%).Some instances that turned into postoperative N0 turned into 11cases(eleven%), N1 turned into 57cases (fifty-seven %), N2 was29 cases (29%) and N3 turned into 3cases (3%).Conclusion: Neo-adjuvant chemotherapy plays a vital role in downstaging of breast and axillary disease, facilitates surgical resection, takes part in pathological entire response and testing response to chemotherapy.

Application of the proposed eighth edition of the American Joint Committee on Cancer/Union of International Cancer Control esophageal cancer staging system in esophageal cancer patients

AbstractObjectiveThe eighth edition of the American Joint Committee on Cancer/Union of International Cancer Control esophageal cancer staging system was proposed in early 2018. The eighth edition staging system includes clinical staging, pathological staging, and neoadjuvant pathological staging, which fills in the blank of non‐operative staging of esophageal cancer. However, there are few reports on the eighth edition of clinical staging, and the purpose of the present study was to verify the prognostic value of the new American Joint Committee on Cancer clinical staging system for esophageal cancer patients who undergo radical radiation therapy.MethodsA total of 544 patients with esophageal cancer from Tianjin Medical University Cancer Institute and Hospital between March 2010 and September 2016 were staged according to the eighth American Joint Committee on Cancer clinical staging system. The Kaplan–Meier method was used to calculate the survival rate of the patients. The Cox regression model was used for multivariate prognostic analysis.ResultsAll the patients were divided into different groups by the eighth American Joint Committee on Cancer clinical tumor–node–metastasis staging system: 40 patients with T2; 157 patients with T3; 347 patients with T4; 132 patients with N0; 193 patients with N1; 172 patients with N2; 47 patients with N3; 81 patients with stage II; 102 patients with state III; and 361 patients with stage IVA. The 3‐year survival rates of stage T2, stage T3, and stage T4 were 60.1%, 45.6%, and 30.8%, respectively (P &lt; 0.001). The 3‐year survival rates of stage N0, stage N1, stage N2, and stage N3 were 48.2%, 40.7%, 29.4%, and 17.3%, respectively (P &lt; 0.001). The 3‐year survival rates of stage II, stage III, and stage IVA were 59.3%, 40.1%, and 31.2%, respectively (P &lt; 0.001). In univariate analysis, age, concurrent chemoradiotherapy, T stage, N stage, Karnofsky marking system, the sixth edition staging system and the eighth edition staging system were important prognostic factors in univariate analyses. In multivariate analysis, concurrent chemotherapy and N stage were important prognostic factors.ConclusionsBased on the data from Tianjin Medical University Cancer Institute and Hospital, the eighth edition clinical staging system had a better predictive ability for esophageal cancer patients who underwent radical radiation therapy.

Normal polysomnography parameters in healthy adults: a systematic review and meta-analysis

Existing normal polysomnography values are not truly normative as they are based on small sample sizes due to the fact that polysomnography is expensive and burdensome to obtain. There is a clear need for a large sample of truly normative data for clinical management and research. This study is a comprehensive meta-analysis of adult polysomnography parameters scored using recent criteria and establishes normative values adjusted for age and sex. For this meta-analysis of adult polysomnography parameters, we searched Scopus for studies of any design published between Jan 1, 2007, and July 31, 2016, that reported polysomnographic parameters scored using recent American Academy of Sleep Medicine criteria (2007 or 2012) collected during an overnight level 1 in-laboratory sleep study in healthy controls. We excluded studies of patients with conditions or subjected to treatments that might affect sleep and studies not available in English. Study endpoints were the pooled estimates of 14 reported polysomnographic parameters. Estimates for each parameter were pooled using a random-effects meta-analysis. The influence of age and sex was ascertained using multivariate mixed-effects meta-regressions. This study is registered with PROSPERO, number CRD42017074319. Of 3712 articles, 169 studies, comprising 5273 participants, were eligible for inclusion. We report normative data stratified by age and sex. For each decade of age, total sleep time decreased by 10·1 min (95% CI 7·5 to 12·8), sleep efficiency decreased by 2·1% (1·5 to 2·6), wake after sleep onset increased by 9·7 min (6·9 to 12·4), sleep onset latency increased by 1·1 min (0·3 to 1·9), arousal index increased by 2·1 events per h (1·5 to 2·6), percentage of N1 sleep increased by 0·5% (0·1 to 0·8), apnea-hypopnea index increased by 1·2 events per h (0·9 to 1·4), mean oxygen saturation decreased by 0·6% (0·5 to 0·7), minimum oxygen saturation decreased by 1·8% (1·3 to 2·3), and periodic limb movement index increased by 1·2 events per h (0·8 to 1·6). Changes with age in the percentage of N2 sleep (0·0%, 95% CI -0·1 to 0·1), N3 sleep (-0·1%, -0·1 to 0·0), and rapid eye movement (REM) sleep (0·0%, -0·1 to 0·0) were not significant. Every 10% increase in the percentage of male participants was associated with reduced REM latency (0·9 min decrease, 95% CI 0·1 to 1·6) and mean oxygen saturation (0·1% decrease, 0·0 to 0·1), and greater arousal index (0·3 events per h, 0·0 to 0·5) and apnea-hypopnea index (0·2 events per h, 0·1 to 0·3). These normative values serve as a useful control reference for clinicians and for future research where it might be difficult to obtain polysomnographic controls. The resulting normative trends by age and sex might also be hypothesis-generating for a broad range of investigations. None.

Microstructure of cortical activity during sleep reflects respiratory events and state of daytime vigilance

Besides visual sleep stage scoring, it is possible to separate sleep stages by analyzing spatially distributed three-channel electroencephalogram (EEG) root mean square (RMS) amplitudes. This approach allows qualitative and quantitative evaluation of sleep architecture. The aim of this study was to analyze the effect of apnea–hypopnea index (AHI) and state of vigilance on the microstructure of cortical activity during sleep using EEG cluster analysis. In 31 obstructive sleep apnea (OSA) patients, cortical EEG patterns were recorded during polysomnography and subjected to EEG cluster analysis. The results were subsequently correlated to AHI as well as to subjective (Epworth Sleepiness Scale) and objective (pupillographic sleepiness test) daytime sleepiness using linear regression. In 18/31 patients, cortical EEG patterns were recorded again the following night during continuous positive airway pressure (CPAP) titration and compared to the results of the first night. Linear regression analyses revealed dependencies of specific cortical EEG patterns on AHI (intra-cluster distance of N2 [p = 0.019], N3 [p = 0.024]; inter-cluster distance of wake-N2 [p = 0.046], wake-N3 [p = 0.047], N2–N3 [p = 0.021]) and on objective daytime sleepiness (wake intra-cluster distance [p = 0.047], inter-cluster distance of wake-N3 [p = 0.042]), but not on subjective daytime sleepiness. Specifically, an increase in EEG pattern variability was found in patients with high AHI values, which could be reduced by CPAP therapy. This new approach enables objective analysis and visualization of sleep macro- and microstructure. The variance of neuronal EEG signal patterns enables conclusions on the presence of pathological respiratory events and objectively measured daytime sleepiness.

Smiling asleep: A study of happy emotional expressions during adult sleep.

Human foetuses and newborns smile first during sleep, before they smile while awake and interacting with caregivers. Whether smiling persists during adult sleep, and expresses inner joy, is yet unknown. Smiles were looked for during night-time video-polysomnography combined with electromyography of the zygomatic and orbicularis oculi muscles in 100 controls, 22 patients with sleepwalking and 52 patients with rapid eye movement (REM) sleep behaviour disorder. Autonomous reactions (heart rate and level of vasoconstriction) and the presence of rapid eye movements were examined during smiles and laughs. On visual examination of the face video clips synchronous with zygomatic contraction, 8% of controls smiled while asleep (7% in REM sleep and 1% in non-REM sleep). Some patients with sleepwalking also smiled and laughed during N2 sleep and N3 parasomnia. Half of the patients with REM sleep behaviour disorder smiled and one-third laughed, mostly during REM sleep. The 173 happy faces included mild smiles (24.8%), open-mouth smiles (29.5%) and laughs (45.7%). More than half of the smiles were the Duchenne (genuine) type, including an active closure of the eyelids. Approximately half of the smiles and laughs were temporally associated with rapid eye movements. There was no increased heart rate variability during smiles and laughs. Two scenic behaviours including smiles and laughs suggested that the happy facial expression was associated with a happy dreaming scenario. Smiling and laughing occasionally persist during adult sleep. There are several lines of evidence suggesting that these happy emotional expressions reflect a true inner mirth.

N4 -Tetradentate Chelators Efficiently Regulate Copper Homeostasis and Prevent ROS Production Induced by Copper-Amyloid-β1-16.

The disruption of copper homeostasis and the oxidative stress induced by Cu-amyloids are crucial features of Alzheimer's disease pathology. The copper specific N4 -tetradendate ligands TDMQ20 and 1 are able to fully inhibit in vitro the aerobic oxidation of ascorbate induced by Cu-Aβ1-16 , even in the presence of 100 molar equivalents of ZnII with respect to CuII , whereas other ligands with N2 O2 or N3 O2 coordination spheres failed to do so. This essential result indicates that, in addition to metal selectivity, the coordination sphere of copper chelators should exhibit a N4 -tetradendate motif to be able to reduce an oxidative stress in the zinc-rich physiological environment of brain. The N4 -scaffolds of these two aminoquinoline-based ligands, TDMQ20 or 1, suitable for a square-planar coordination of copper(II), allowed them to enhance both the selectivity for copper and the ability to reduce the oxidative stress induced by copper-amyloid in a zinc-rich environment.

Semidefinite bounds for mixed binary/ternary codes

For nonnegative integers n2,n3 and d, let N(n2,n3,d) denote the maximum cardinality of a code of length n2+n3, with n2 binary coordinates and n3 ternary coordinates (in this order) and with minimum distance at least d. For a nonnegative integer k, let Ck denote the collection of codes of cardinality at most k. For D∈Ck, define S(D)≔{C∈Ck∣D⊆C,|D|+2|C∖D|≤k}. Then N(n2,n3,d) is upper bounded by the maximum value of ∑v∈[2]n2[3]n3x({v}), where x is a function Ck→R such that x(∅)=1 and x(C)=0 if C has minimum distance less than d, and such that the S(D)×S(D) matrix (x(C∪C′))C,C′∈S(D) is positive semidefinite for each D∈Ck. By exploiting symmetry, the semidefinite programming problem for the case k=3 is reduced using representation theory. It yields 135 new upper bounds that are provided in tables.

Role of Bone Scintigraphy in Modification and Finalization of the Pathological Staging of Carcinoma of Breast

&lt;p&gt;&lt;strong&gt;Objectives: &lt;/strong&gt;The prognosis and treatment planning of carcinoma depends upon the stage of the disease. The presence of bone metastasis affects a patient’s prognosis and further treatment planning. The purpose of this study was whether bone scintigraphy by detecting skeletal metastasis can help in patient management by modification of initial pathological staging.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Patients and Methods: &lt;/strong&gt;A total of 110 patients of breast carcinoma who were referred for the early bone scintigraphy after the surgical procedure were included in this study. Bone scintigraphy was done 3 hours after 15 m Ci Tc-99m methylelene diphosphonate (MDP) intravenous injection. Images were acquired in Siemens E-cam dual head camera. Chi-Square test was used to analyze the variables&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Out of the total 110 patients with breast carcinoma referred to the institute after initial pathological staging nearly one third i.e. 31 (28.2%) patients had skeletal metastasis. In this study it was revealed that tumour size and nodal involvement correlated well with metastasis to bone. Skeletal metastasis was significantly (p&amp;lt;0.05) higher in tumour size belonged to &amp;gt;3.0 – ≥5.0 cm and nodal involvement N2–N3(p&amp;lt;0.05). Sixty eught of the patients were in pathological stage II, among them 22.1% of the patients had skeletal metastasis. Pathological stage III was observed in 33 cases, among them 48.5% patients had skeletal metastasis and as thus staging was modified by bone scintigraphy in 22.1% in stage II and 48.5% in stage III. Pathological stage I was in 9 cases among them no metastasis was observed.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion:&lt;/strong&gt; Bone scintigraphy is a useful imaging modality in staging of breast carcinoma. It is recommended in patients with stage II and above and this can influence the clinical management.&lt;/p&gt;&lt;p&gt;Bangladesh J. Nuclear Med. 19(2): 107-110, July 2016&lt;/p&gt;

Nationwide multicenter study on the management of pulmonary neuroendocrine (carcinoid) tumors.

Background and aimTo analyze the management and outcome of patients with primary typical (TC) and atypical lung carcinoids (AC) in Switzerland.MethodsRetrospective analysis of patients selected from a neuroendocrine tumor (NET) registry. Patients were divided into TC and AC according to pathology reports, and surgical procedures were grouped as wedge/segmentectomy, lobectomy/bilobectomy and pneumectomy. Survival analysis was performed using the Kaplan–Meier method and log-rank test.ResultsOver 7 years, 113 pulmonary carcinoids (61.9% females, mean age 59.4 years) were included from 19 hospitals, with pathology data on Ki67 and necrosis incomplete in 16 cases. Eighty-three TC and 14 AC underwent surgical resection with a primary tumor size of median 14.5 (range 1–80) mm and diagnosis was established in 55.8% at surgery. Mean follow-up was 30.2 ± 23.1 months. Lobectomy was performed in 54.2% and wedge resection in 17.7% of cases. Six patients received additional systemic therapy. There was a trend for larger primary lesion size and a significantly higher rate of N2–N3 status in AC. Mean survival tended to be increased in patients with TC compared to AC (86.1 vs 48.4 months, P = 0.06) and mean disease-free interval after surgical resection was 74.1 and 48.3 months for TC and AC, respectively (P = 0.74).ConclusionAC of the lung has a more malignant behavior and a trend to a worse outcome. The results of this registry reinforce the need for standardized histological diagnosis and inter-disciplinary therapeutic decision making to improve the quality of care of patients with TC and AC.

Sleepless Night and Day, the Plight of Progressive Supranuclear Palsy.

To elucidate the unique sleep and waking characteristics in progressive supranuclear palsy (PSP), a neurodegenerative disease associated with motor deficits and dementia that largely affects the brainstem and thalamic regions. A total of 20 PSP and 16 healthy older adult controls participated in this study. The participants underwent an overnight polysomnography and multiple sleep latency test (MSLT) the following day. Prior to the MSLT last trial, they were asked to complete the Stanford Sleepiness Scale. Data were assessed for measures of latency to sleep onset, sleep duration, waking, and sleep staging during the night. Mean sleep latency, a measure of daytime sleepiness, sleep onset rapid eye movement (REM) periods, and microsleeps were studied with the MSLT. Spectral analysis of wake electroencephalogram (EEG) was performed for 30-second periods at the start of each MSLT trial. PSP took significantly longer time to fall asleep (p < .001), slept less during the night (p ≤ .001), and had more wake after sleep onset than controls (p ≤ .001). PSP had less N2 sleep (p < .05) and N3 sleep (p < .05), and REM sleep (p < .001) than controls. During the MSLT, PSP took significantly longer to fall asleep (p < .001), did not have microsleeps when they remained awake throughout the assessment periods, but were subjectively sleepier than controls (p < .05). Gamma power was increased during wake EEG in PSP (p < .01). Sleep/waking regulation and REM sleep regulation are disrupted in PSP, leading to profound sleep deprivation without recuperation. Our findings suggest a diminished homeostatic sleep drive in PSP. This hyperaroused state is unique and is a severely disabling feature of PSP.

Sleep spindles may predict response to cognitive-behavioral therapy for chronic insomnia

BackgroundWhile cognitive-behavioral therapy for insomnia constitutes the first-line treatment for chronic insomnia, only few reports have investigated how sleep architecture relates to response to this treatment. In this pilot study, we aimed to determine whether pre-treatment sleep spindle density predicts treatment response to cognitive-behavioral therapy for insomnia. MethodsTwenty-four participants with chronic primary insomnia participated in a 6-week cognitive-behavioral therapy for insomnia performed in groups of 4–6 participants. Treatment response was assessed using the Pittsburgh Sleep Quality Index and the Insomnia Severity Index measured at pre- and post-treatment, and at 3- and 12-months' follow-up assessments. Secondary outcome measures were extracted from sleep diaries over 7 days and overnight polysomnography, obtained at pre- and post-treatment. Spindle density during stage N2–N3 sleep was extracted from polysomnography at pre-treatment. Hierarchical linear modeling analysis assessed whether sleep spindle density predicted response to cognitive-behavioral therapy. ResultsAfter adjusting for age, sex, and education level, lower spindle density at pre-treatment predicted poorer response over the 12-month follow-up, as reflected by a smaller reduction in Pittsburgh Sleep Quality Index over time. Reduced spindle density also predicted lower improvements in sleep diary sleep efficiency and wake after sleep onset immediately after treatment. There were no significant associations between spindle density and changes in the Insomnia Severity Index or polysomnography variables over time. ConclusionThese preliminary results suggest that inter-individual differences in sleep spindle density in insomnia may represent an endogenous biomarker predicting responsiveness to cognitive-behavioral therapy. Insomnia with altered spindle activity might constitute an insomnia subtype characterized by a neurophysiological vulnerability to sleep disruption associated with impaired responsiveness to cognitive-behavioral therapy.

Pyrrolyl-based pincer complexes of iron – Synthesis and electronic structure

Four- and five-coordinate high-spin (S=2) Fe(II) complexes bearing the pyrrolyl-derived tBuPNP pincer ligand [tBuPNP=2,5-(tBu2PCH2)2(C4H2N)] have been prepared. All three complexes were characterized by X-ray diffraction, zero-field 57Fe Mössbauer spectroscopy and solid-state magnetic susceptibility studies. Furthermore, the experimentally determined Mössbauer parameters of compounds 4–6 can be modeled satisfactorily by density functional theory (DFT) computations at the B97D level of theory. Introduction of the sterically demanding bis(trimethylsilyl)amido moiety induces significant distortions from ideal tetrahedral geometry in [(tBuPNP)FeN(SiMe3)2] (4), featuring an Fe(II) high-spin state with large negative axial zero-field splitting and slow paramagnetic relaxation at low temperature, as evidenced by measurements of the solid-state magnetic susceptibility and zero-field 57Fe Mössbauer spectroscopy. Replacing the chlorido ligand in [(tBuPNP)FeCl] (3) by the bidentate acetylacetonato (acac) ligand enforces a trigonal–bipyramidal structure in [(tBuPNP)Fe(acac)] (5), in which the Fe(II) atom also adopts a high-spin configuration. Reaction of 3 with adamantyl azide allowed us to confirm the inherent lability of the phosphine coordination, since the azide inserts into the FeP bond to form [(tBuPNPN3Adamantyl)FeCl] (6), in which the tBuPNP ligand is transformed to a phosphino-pyrrolyl-phosphazide ligand framework (tBuPNPN3Adamantyl). This motif can be considered as a trapped Staudinger intermediate along the reaction pathway of free phosphines with organic azides to form phosphinimines. Bidentate binding of the phosphazide sidearm in κN:κN-fashion to the Fe(II) atom enforces an s-anti coordination of the P1–N2–N3–N4 moiety, which raises the barrier for the thermodynamically favorable N2 elimination and allows this intermediate to be trapped. Complex 6 contains a high-spin Fe(II) atom with a square-pyramidal structure.

Upfront vs. no upfront neck dissection in primary head and neck cancer radio(chemo)therapy: Tumor control and late toxicity

Purpose/objectiveThe benefit of upfront neck dissection (ND) in locally advanced head and neck squamous cell carcinoma (HNSCC) treated with primary (chemo-) radiotherapy (R(C)T) is debated. Therefore, we retrospectively compared disease control and toxicity between patients who were treated with and without upfront ND followed by R(C)T. Material/methodsTwo-hundred sixty-four consecutive patients with HNSCC without distant metastases at diagnosis and with lymph node stage N2–N3 were included in 2 centers. Patients were all treated between January 2002 and December 2012, and received definitive R(C)T in center 1 and upfront ND followed by R(C)T in center 2. Clinical data and outcome were assessed retrospectively. Toxicity was scored using the LENT-SOMA scale at 6, 12, 18 and 24months following the end of treatment. ResultsWe included 150 patients in the group without ND (center 1) and 114 patients in the group with upfront ND (center 2).Mean follow up was 5.68years in the group without ND and 5.83years in the group with upfront ND. Local, regional and distant control after 2years were 91.07% and 85.96% (p=0.09), 89.22% and 83.27% (p=0.12) and 76.74% and 75.13% (p=0.92) in the group with and without upfront ND, respectively.We did not find a significant difference between both groups regarding edema and atrophy at 6, 12, 18 and 24months. We found a trend at all time-points toward worse outcome in the ND group at all time-points (p=0.06). A significantly higher proportion of moderate to severe fibrosis (grade ≥2) was present in the ND group (p=0.01) at all time points. ConclusionThere was no significant difference in local, regional or distant control and disease-free survival between both patient populations. Fibrosis, specifically fibrosis grade ≥2 is more prominent following upfront ND and R(C)T when compared to R(C)T alone.

Sleep spindle detection based on non-experts: A validation study.

Accurate and efficient detection of sleep spindles is a methodological challenge. The present study describes a method of using non-experts for manual detection of sleep spindles. We recruited five experts and 168 non-experts to manually identify spindles in stage N2 and stage N3 sleep data using a MATLAB interface. Scorers classified each spindle into definite and indefinite spindle (with weights of 1 and 0.5, respectively). First, a method of optimizing the thresholds of the expert/non-expert group consensus according to the results of experts and non-experts themselves is described. Using this method, we established expert and non-expert group standards from expert and non-expert scorers, respectively, and evaluated the performance of the non-expert group standards by compared with the expert group standard (termed EGS). The results indicated that the highest performance was the non-expert group standard when definite spindles were only considered (termed nEGS-1; F1 score = 0.78 for N2; 0.68 for N3). Second, four automatic spindle detection methods were compared with the EGS. We found that the performance of nEGS-1 versus EGS was higher than that of the four automated methods. Our results also showed positive correlation between the mean F1 score of individual expert in EGS and the F1 score of nEGS-1 versus EGS across 30 segments of stage N2 data (r = 0.61, P < 0.001). Further, we found that six and nine non-experts were needed to manually identify spindles in stages N2 and N3, respectively, while maintaining acceptable performance of nEGS-1 versus EGS (F1 score = 0.79 for N2; 0.64 for N3). In conclusion, this study establishes a detailed process for detection of sleep spindles by non-experts in a crowdsourcing scheme.

Comparison of different lymph node staging systems in prognosis of gastric cancer: a bi-institutional study from Hungary.

ObjectiveThe Union for International Cancer Control (UICC) Node (N) classification is the most common used staging method for the prognosis of gastric cancer. It demands adequate, at least 16 lymph nodes (LNs) to be dissected; therefore different staging systems were invented.MethodsBetween March 2005 and March 2010, 164 patients were evaluated at the Department of General Surgery in the Kenézy Gyula Hospital and at the Department of General, Thoracic and Vascular Surgery in the Kaposi Mór Hospital. The 6th, 7th and 8th UICC N-staging systems, the number of examined LNs, the number of harvested negative LNs, the metastatic lymph node ratio (MLR) and the log odds of positive LNs (LODDS) were determined to measure their 5-year survival rates and to compare them to each other.ResultsThe overall 5-year survival rate for all patients was 55.5% with a median overall survival time of 102 months. The tumor stage, gender, UICC N-stages, MLR and the LODDS were significant prognostic factors for the 5-year survival with univariate analysis. The 6th UICC N-stage did not follow the adequate risk in comparing N2 vs. N0 and N3 vs. N0 with multivariate investigation. Comparison of performances of the residual N classifications proved that the LODDS system was first in the prediction of prognosis during the evaluation of all patients and in cases with less than 16 harvested LNs. The MLR gave the best prognostic prediction when adequate (more than or equal to 16) lymphadenectomy was performed. ConclusionsWe suggest the application of LODDS system routinely in western patients and the usage of MLR classification in cases with extended lymphadenectomy.

Initial mechanisms for the unimolecular decomposition of electronically excited nitrogen-rich energetic salts with tetrazole rings: (NH4)2BT and TAGzT

Unimolecular decomposition of nitrogen-rich energetic salt molecules bis(ammonium)5,5′-bistetrazolate (NH4)2BT and bis(triaminoguanidinium) 5,5′-azotetrazolate TAGzT, has been explored via 283 nm laser excitation. The N2 molecule, with a cold rotational temperature (&amp;lt;30 K), is observed as an initial decomposition product, subsequent to UV excitation. Initial decomposition mechanisms for the two electronically excited salt molecules are explored at the complete active space self-consistent field (CASSCF) level. Potential energy surface calculations at the CASSCF(12,8)/6-31G(d) ((NH4)2BT) and ONIOM (CASSCF/6-31G(d):UFF) (TAGzT) levels illustrate that conical intersections play an essential role in the decomposition mechanism as they provide non-adiabatic, ultrafast radiationless internal conversion between upper and lower electronic states. The tetrazole ring opens on the S1 excited state surface and, through conical intersections (S1/S0)CI, N2 product is formed on the ground state potential energy surface without rotational excitation. The tetrazole rings open at the N2—N3 ring bond with the lowest energy barrier: the C—N ring bond opening has a higher energy barrier than that for any of the N—N ring bonds: this is consistent with findings for other nitrogen-rich neutral organic energetic materials. TAGzT can produce N2 either by the opening of tetrazole ring or from the N=N group linking its two tetrazole rings. Nonetheless, opening of a tetrazole ring has a much lower energy barrier. Vibrational temperatures of N2 products are hot based on theoretical predictions. Energy barriers for opening of the tetrazole ring for all the nitrogen-rich energetic materials studied thus far, including both neutral organic molecules and salts, are in the range from 0.31 to 2.71 eV. Energy of the final molecular structure of these systems with dissociated N2 product is in the range from −1.86 to 3.11 eV. The main difference between energetic salts and neutral nitrogen-rich energetic material is that energetic salts usually have lower excitation energy.

Down-regulation of miR-133a as a poor prognosticator in non-small cell lung cancer

miR-133a has been demonstrated to play an important role in tumor progression. The aim of present study was to analyze the correlation between miR-133a expression level and clinicopathologic features and its prognostic significance in non-small cell lung cancer (NSCLC). The expression of miR-133a in 104 pairs of human lung cancer tissues and adjacent normal lung tissues were analyzed by qRT-PCR. Here we show that miR-133a was down-regulated in NSCLC. The levels of miR-133a were negatively correlated with the status of N classification (N0–N1 vs. N2–N3, P=0.000), clinical stage (I–II vs. III–IV, P=0.010) and MMP-14 expression (High vs. Low, P=0.012). The patients with low miR-133a expression had shorter survival time than those with high miR-133a expression. Multivariate analysis indicated that the level of miR-133a expression was an independent prognostic indicator (P=0.012) for the survival of patients with NSCLC. In conclusion, decreased expression of miR-133a might be a potential unfavorable prognostic factor for patients with NSCLC, and further studies would be needed to prove our findings.

Origin and switch of different colors: Thermo-isomerism and crystal structure of (1E,2E)-bis[1-(4-nitrophenyl)ethylidene] hydrazine

A new symmetric branched 4-nitrophenyl hydrazine compound has been prepared in one-step procedure by direct condensation of aromatic ketone with hydrazine in MeOH. The synthesized compound, red isomer, was characterized by IR, 1H and 13C NMR spectroscopy, Elemental analyses, Mass spectrometry and X-ray crystallography. Refluxing in MeOH solution led to thermo-isomerism offering a white isomer product that was characterized by X-ray crystallography. The red isomer crystallizes in the orthorhombic system having space group Pbcn, with a = 12.7612(4), b = 11.5197(3), c = 20.1586(7) A, V = 2963.42(16) A 3, Z = 8 while the white isomer crystallizes in the triclinic system having space group P −1, with a = 7.8007(4), 8.5966(7), 12.224 (1) A, α= 71.133(7), β= 81.281(5), γ= 74.895(5) ∘, V = 746.86(9) A 3, Z = 2. Molecules of both compounds are twisted at N2–N3 bond with the C7-N2-N3-C9 torsion angle of 155.23(12) and −113.36(18) ∘, respectively. The crystal structures of both compounds are stabilized by weak intramolecular C—H …N contacts and intermolecular C—H …O hydrogen bonding interactions. In addition, π– π stacking interactions are observed between the same aromatic rings of molecules.