A syntactic realization theorem for justification logics

Justification logics are refinements of modal logics where modalities are replaced by justification terms. They are connected to modal logics via so-called realization theorems. We present a syntactic proof of a single realization theorem that uniformly connects all the normal modal logics formed from the axioms \$mathsfd\$, \$mathsft\$, \$mathsfb\$, \$mathsf4\$, and \$mathsf5\$ with their justification counterparts. The proof employs cut-free nested sequent systems together with Fitting's realization merging technique. We further strengthen the realization theorem for \$mathsfKB5\$ and \$mathsfS5\$ by showing that the positive introspection operator is superfluous.

Giant cell glioblastoma in the cerebrum of a pembroke welsh corgi

A 6-year-old, neutered female Pembroke Welsh corgi was presented with a 1-month history of ataxia and panting. The clinical signs progressed until the dog became anorexic, obtunded and exhibited circling to the left. At necropsy examination, a mass was detected in the left forebrain, impinging on the cribriform plate. Microscopically, the mass was composed of sheets of round to pleomorphic neoplastic cells with vacuolated cytoplasm. Nuclear atypia, anisocytosis and anisokaryosis were common. Numerous bizarre, multinucleated giant cells containing 60 or more nuclei and giant mononuclear cells were present. The matrix contained abundant reticulin. Immunohistochemistry revealed the neoplastic cells uniformly to express vimentin, and a small number of neoplastic cells expressed glial fibrillary acid protein. A diagnosis of giant cell glioblastoma was made. Although well recognized in man, this tumour has been documented rarely in the veterinary literature.

Role and extent of lymphadenectomy during radical cystectomy for invasive bladder cancer

There is substantial variability in the extent of the node dissection performed during radical cystectomy for bladder cancer. Here, we review the diagnostic assessment of lymph node metastasis and the prognostic and therapeutic benefit for pelvic node dissection for bladder cancer. A review of the applicable urologic literature regarding the topics of lymphadenectomy for bladder cancer was conducted. Nodal metastasis above a limited or standard template is not uncommon, with up to 16% of all nodal metastasis detected proximal to the aortic bifurcation. However, skip metastasis is extremely rare. Proteins associated purely with epithelial tissue such as cytokeratin (CK)-19, CK-20, and uroplakin II have been observed in reportedly negative nodal specimens, which indicates that routine microscopic analysis of nodal tissue may miss small foci of metastatic cancer. In addition to the surgical technique, the total number of lymph nodes removed is influenced by patient anatomy and pathologic processing and therefore may be unsuitable as a procedural quality statement. Consecutively, meticulous removal of tissue within a defined and uniformly applied template may be more relevant than absolute nodal count. Observational cohort series indicate an improved oncologic outcome for patients undergoing extensive nodal dissection. The results of two randomized controlled trials addressing the extent of nodal dissection for bladder cancer are forthcoming.

The effects of dexmedetomidine/remifentanil and midazolam/remifentanil on auditory-evoked potentials and electroencephalogram at light-to-moderate sedation levels in healthy subjects

Avoidance of excessively deep sedation levels is problematic in intensive care patients. Electrophysiologic monitoring may offer an approach to solving this problem. Since electroencephalogram (EEG) responses to different sedation regimens vary, we assessed electrophysiologic responses to two sedative drug regimens in 10 healthy volunteers. Dexmedetomidine/remifentanil (dex/remi group) and midazolam/remifentanil (mida/remi group) were infused 7 days apart. Each combination of medications was given at stepwise intervals to reach Ramsay scores (RS) 2, 3, and 4. Resting EEG, bispectral index (BIS), and the N100 amplitudes of long-latency auditory-evoked potentials (ERP) were recorded at each level of sedation. During dex/remi, resting EEG was characterized by a recurrent high-power low-frequency pattern which became more pronounced at deeper levels of sedation. BIS Index decreased uniformly in only the dex/remi group (from 94 +/- 3 at baseline to 58 +/- 14 at RS 4) compared to the mida/remi group (from 94 +/- 2 to 76 +/- 10; P = 0.029 between groups). The ERP amplitudes decreased from 5.3 +/- 1.3 at baseline to 0.4 +/- 1.1 at RS 4 (P = 0.003) in only the mida/remi group. We conclude that ERPs in volunteers sedated with dex/remi, in contrast to mida/remi, indicate a cortical response to acoustic stimuli, even when sedation reaches deeper levels. Consequently, ERP can monitor sedation with midazolam but not with dexmedetomidine. The reverse is true for BIS.

A modified test for small-study effects in meta-analyses of controlled trials with binary endpoints

Publication bias and related bias in meta-analysis is often examined by visually checking for asymmetry in funnel plots of treatment effect against its standard error. Formal statistical tests of funnel plot asymmetry have been proposed, but when applied to binary outcome data these can give false-positive rates that are higher than the nominal level in some situations (large treatment effects, or few events per trial, or all trials of similar sizes). We develop a modified linear regression test for funnel plot asymmetry based on the efficient score and its variance, Fisher's information. The performance of this test is compared to the other proposed tests in simulation analyses based on the characteristics of published controlled trials. When there is little or no between-trial heterogeneity, this modified test has a false-positive rate close to the nominal level while maintaining similar power to the original linear regression test ('Egger' test). When the degree of between-trial heterogeneity is large, none of the tests that have been proposed has uniformly good properties.

Uniform vascular-endothelial-cell-specific gene expression in both embryonic and adult transgenic mice

TIE2 is a vascular endothelial-specific receptor tyrosine kinase essential for the regulation of vascular network formation and remodeling. Previously, we have shown that the 1.2-kb 5' flanking region of the TIE2 promoter is capable of directing beta-galactosidase reporter gene expression specifically into a subset of endothelial cells (ECs) of transgenic mouse embryos. However, transgene activity was restricted to early embryonic stages and not detectable in adult mice. Herein we describe the identification and characterization of an autonomous endothelial-specific enhancer in the first intron of the mouse TIE2 gene. Furthermore, combination of the TIE2 promoter with an intron fragment containing this enhancer allows it to target reporter gene expression specifically and uniformly to virtually all vascular ECs throughout embryogenesis and adulthood. To our knowledge, this is the first time that an in vivo expression system has been assembled by which heterologous genes can be targeted exclusively to the ECs of the entire vasculature. This should be a valuable tool to address the function of genes during physiological and pathological processes of vascular ECs in vivo. Furthermore, we were able to identify a short region critical for enhancer function in vivo that contains putative binding sites for Ets-like transcription factors. This should, therefore, allow us to determine the molecular mechanisms underlying the vascular-EC-specific expression of the TIE2 gene.

Lung aeration during sleep

BACKGROUND: During sleep, ventilation and functional residual capacity (FRC) decrease slightly. This study addresses regional lung aeration during wakefulness and sleep. METHODS: Ten healthy subjects underwent spirometry awake and with polysomnography, including pulse oximetry, and also CT when awake and during sleep. Lung aeration in different lung regions was analyzed. Another three subjects were studied awake to develop a protocol for dynamic CT scanning during breathing. RESULTS: Aeration in the dorsal, dependent lung region decreased from a mean of 1.14 +/- 0.34 mL (+/- SD) of gas per gram of lung tissue during wakefulness to 1.04 +/- 0.29 mL/g during non-rapid eye movement (NREM) sleep (- 9%) [p = 0.034]. In contrast, aeration increased in the most ventral, nondependent lung region, from 3.52 +/- 0.77 to 3.73 +/- 0.83 mL/g (+ 6%) [p = 0.007]. In one subject studied during rapid eye movement (REM) sleep, aeration decreased from 0.84 to 0.65 mL/g (- 23%). The fall in dorsal lung aeration during sleep correlated to awake FRC (R(2) = 0.60; p = 0.008). Airway closure, measured awake, occurred near and sometimes above the FRC level. Ventilation tended to be larger in dependent, dorsal lung regions, both awake and during sleep (upper region vs lower region, 3.8% vs 4.9% awake, p = 0.16, and 4.5% vs 5.5% asleep, p = 0.09, respectively). CONCLUSIONS: Aeration is reduced in dependent lung regions and increased in ventral regions during NREM and REM sleep. Ventilation was more uniformly distributed between upper and lower lung regions than has previously been reported in awake, upright subjects. Reduced respiratory muscle tone and airway closure are likely causative factors.

A call for uniform reporting standards in studies assessing endovascular treatment for chronic ischaemia of lower limb arteries

Endovascular therapy is a rapidly evolving field for the treatment of patients with peripheral arterial disease, and a magnitude of studies reporting on various modern revascularization concepts have been recently published. Thus, studies assessing the efficacy of endovascular therapy of peripheral arteries do not operate with uniformly defined endpoints, rendering a direct comparison of studies difficult. The purpose of this consensus statement is to highlight differences in the terminology used in the current literature and to propose some standardized criteria that must be considered when reporting results of endovascular revascularization for chronic ischaemia of lower limb arteries.

Immunohistochemical demonstration of interleukin-1 beta induced changes in acute-phase proteins and albumin in rat liver

Interleukin-1 beta is a potent mediator of the acute-phase response. However, the effects of interleukin-1 beta administration on the topic in vivo production of acute-phase proteins and albumin are so far not well understood. Overnight fasted rats were subcutaneously injected with 0.2 mL 0.9% NaCl (control group) or 6.25 micrograms recombinant human interleukin-1 beta, and rectal temperature was measured at intervals up to 48 h. Livers were perfused-fixed in vivo prior to injection (base-line), and at 9, 24, and 48 h following the interleukin-1 beta injection. Fibrinogen, orosomucoid (alpha 1-acid glycoprotein) and albumin were immunostained using a streptavidin-biotin-immunoperoxidase technique. Rectal temperature peaked 5 h after the single interleukin-1 beta injection, and fell gradually to base-line values by 24 h. Prior to injection only a few hepatocytes, randomly scattered throughout the liver lobule, stained positive for fibrinogen and orosomucoid. In contrast, all hepatocytes stained uniformly positive for fibrinogen and orosomucoid 9 h after interleukin-1 beta injection, whereas at 24 h a predominant centrilobular staining pattern occurred. Due to fasting, albumin positive hepatocytes were already reduced at base-line in both groups. Interleukin-1 beta induced a further significant loss of albumin positive cells in the periportal zone (35 +/- 21%) at 9 h when compared with controls (58 +/- 11%, p = 0.037). In conclusion, subcutaneous interleukin-1 beta (probably by stimulation of interleukin-6) strongly induces fibrinogen and orosomucoid expression in rat liver, and suppresses immunohistochemically stainable albumin in a heterogenous way, mainly in the periportal zone.

From Statistical Data to Spatial Knowledge - informing decision making in Vietnam

Vietnam has developed rapidly over the past 15 years. However, progress was not uniformly distributed across the country. Availability, adequate visualization and analysis of spatially explicit data on socio-economic and environmental aspects can support both research and policy towards sustainable development. Applying appropriate mapping techniques allows gleaning important information from tabular socio-economic data. Spatial analysis of socio-economic phenomena can yield insights into locally-specifi c patterns and processes that cannot be generated by non-spatial applications. This paper presents techniques and applications that develop and analyze spatially highly disaggregated socioeconomic datasets. A number of examples show how such information can support informed decisionmaking and research in Vietnam.

Durability and outcome of initial antiretroviral treatments received during 2000--2005 by patients in the Swiss HIV Cohort Study

BACKGROUND: Little is known about time trends, predictors, and consequences of changes made to antiretroviral therapy (ART) regimens early after patients initially start treatment. METHODS: We compared the incidence of, reasons for, and predictors of treatment change within 1 year after starting combination ART (cART), as well as virological and immunological outcomes at 1 year, among 1866 patients from the Swiss HIV Cohort Study who initiated cART during 2000--2001, 2002--2003, or 2004--2005. RESULTS: The durability of initial regimens did not improve over time (P = .15): 48.8% of 625 patients during 2000--2001, 43.8% of 607 during 2002--2003, and 44.3% of 634 during 2004--2005 changed cART within 1 year; reasons for change included intolerance (51.1% of all patients), patient wish (15.4%), physician decision (14.8%), and virological failure (7.1%). An increased probability of treatment change was associated with larger CD4+ cell counts, larger human immunodeficiency virus type 1 (HIV-1) RNA loads, and receipt of regimens that contained stavudine or indinavir/ritonavir, but a decreased probability was associated with receipt of regimens that contained tenofovir. Treatment discontinuation was associated with larger CD4+ cell counts, current use of injection drugs, and receipt of regimens that contained nevirapine. One-year outcomes improved between 2000--2001 and 2004--2005: 84.5% and 92.7% of patients, respectively, reached HIV-1 RNA loads of <50 copies/mL and achieved median increases in CD4+ cell counts of 157.5 and 197.5 cells/microL, respectively (P < .001 for all comparisons). CONCLUSIONS: Virological and immunological outcomes of initial treatments improved between 2000--2001 and 2004--2005, irrespective of uniformly high rates of early changes in treatment across the 3 study intervals.

A novel exposure system for the efficient and controlled deposition of aerosol particles onto cell cultures

Epidemiologic studies have shown correlations between morbidity and particles < or = 2.5 microm generated from pollution processes and manufactured nanoparticles. Thereby nanoparticles seem to play a specific role. The interaction of particles with the lung, the main pathway of undesired particle uptake, is poorly understood. In most studies investigating these interactions in vitro, particle deposition differs greatly from the in vivo situation, causing controversial results. We present a nanoparticle deposition chamber to expose lung cells mimicking closely the particle deposition conditions in the lung. In this new deposition chamber, particles are deposited very efficiently, reproducibly, and uniformly onto the cell culture, a key aspect if cell responses are quantified in respect to the deposited particle number. In situ analyses of the lung cells, e.g., the ciliary beat frequency, indicative of the defense capability of the cells, are complemented by off-line biochemical, physiological, and morphological cell analyses.

The etiology of liver damage imparts cytokines transforming growth factor beta1 or interleukin-13 as driving forces in fibrogenesis

It is unknown whether transforming growth factor beta1 (TGF-beta1) signaling uniformly participates in fibrogenic chronic liver diseases, irrespective of the underlying origin, or if other cytokines such as interleukin (IL)-13 share in fibrogenesis (e.g., due to regulatory effects on type I pro-collagen expression). TGF-beta1 signaling events were scored in 396 liver tissue samples from patients with diverse chronic liver diseases, including hepatitis B virus (HBV), hepatitis C virus (HCV), Schistosoma japonicum infection, and steatosis/steatohepatitis. Phospho-Smad2 staining correlated significantly with fibrotic stage in patients with HBV infection (n = 112, P < 0.001) and steatosis/steatohepatitis (n = 120, P < 0.01), but not in patients with HCV infection (n = 77, P > 0.05). In tissue with HBx protein expression, phospho-Smad2 was detectable, suggesting a functional link between viral protein expression and TGF-beta1 signaling. For IL-13, immunostaining correlated with fibrotic stage in patients with HCV infection and steatosis/steatohepatitis. IL-13 protein was more abundant in liver tissue lysates from three HCV patients compared with controls, as were IL-13 serum levels in 68 patients with chronic HCV infection compared with 20 healthy volunteers (72.87 +/- 26.38 versus 45.41 +/- 3.73, P < 0.001). Immunohistochemistry results suggest that IL-13-mediated liver fibrogenesis may take place in the absence of phospho-signal transducer and activator of transcription protein 6 signaling. In a subgroup of patients with advanced liver fibrosis (stage > or =3), neither TGF-beta nor IL-13 signaling was detectable. Conclusion: Depending on the cause of liver damage, a predominance of TGF-beta or IL-13 signaling is found. TGF-beta1 predominance is detected in HBV-related liver fibrogenesis and IL-13 predominance in chronic HCV infection. In some instances, the underlying fibrogenic mediator remains enigmatic.