09, 0 20) A similar analysis between a type 1 endplate and the p

09, 0.20). A similar analysis between a type 1 endplate and the presence of a disk herniation (PPV, 0.26; 95% CI: 0.19, 0.34) and between a type 1 endplate and vertebral body spondylolisthesis (PPV, 0.28; 95% CI: 0.20, 0.35) were significant.

Conclusion: Type 1 signal intensity changes on MR images have a high positive predictive value in the identification of a pain generator. (c) RSNA, 2009″
“Metal/insulator/metal thin film stacks showing stable resistive switching are promising candidates for future use as a nonvolatile resistive random access memory, competitive to FLASH and DRAM. Although the switching mechanisms are not completely understood a lot

of theories GW3965 solubility dmso and models try to describe the effects. One of them postulates the trapping and detrapping of electronic charge in immobile traps as the reason for the resistance changes, also known as Simmons & Verderber model. This contribution shows that this “”pure electronic”" switching mechanism will face a voltage-time dilemma-general to all switching insulators-at conditions competitive to the state-of-the-art FLASH. There is an incompatibility

between the long retention time (10 years) and Smoothened Agonist in vivo the short READ/WRITE current pulses (t(READ/WRITE) <= 100 ns) at high densities (area <= 100 x 100 nm(2)) at low applied voltages (<= 1 V). This general dilemma is exemplified in two detailed scenarios with different electronic band and defect properties. (C) 2010 American Institute of Physics. [doi: 10.1063/1.3319591]“
“BACKGROUND: Pulmonary hypertension may occur in patients with interstitial pneumonia and is associated with increased mortality. We sought to determine the prevalence of pulmonary hypertension in

sub-groups of patients with interstitial pneumonia and to investigate possible associations between pulmonary vascular hemodynamics and pulmonary function.

METHODS: The presence or absence of pulmonary hypertension was assessed in 70 patients with advanced interstitial pneumonia who underwent right heart catheterization. The associations of pulmonary hypertension with clinical characteristics and pulmonary function tests were analyzed.

RESULTS: The prevalence of pulmonary hypertension check details in patients with idiopathic interstitial pneumonia was 29% vs 64% in patients with connective tissue disease-interstitial pneumonia (p = 0.013). African American patients had a significantly higher prevalence of pulmonary hypertension in the entire study population (81% vs 22%, p < 0.001) and in the idiopathic interstitial pneumonia group (70% vs 19%, p < 0.01). Regression analyses revealed no association between mean pulmonary artery pressure (mPAP) and forced vital capacity or mPAP and diffusion capacity of the lung for carbon monoxide in the entire cohort or in sub-groups of patients.

CONCLUSIONS: African American patients and patients with connective tissue disease-interstitial pneumonia had a high prevalence of pulmonary hypertension.

Embryo development is initially regulated by maternal transcripts

Embryo development is initially regulated by maternal transcripts until replaced by embryonic genomic expression. this website Then, an assortment of hormones and local environmental factors in various concentrations along the reproductive tract (e.g. fallopian tube, endometrial lining) provide the protection, nutrients and means of communication for the embryo to implant and develop. Both oocytes and embryos are susceptible to environmental, occupational and lifestyle exposures that can exert direct toxic effects and disrupt

hormones. While some exposures may produce reversible changes, others, especially those damaging germinal cells in utero or during prepuberty, may result in permanent sequelae GSK1210151A purchase that continue in future generations. This article reviews the main factors that affect female fertility and their possible influence on human reproduction. Some lifestyles, xeno-oestrogens and heavy metals are already known to compromise female reproductive function. Nonetheless, many questions remain and little is known about the effect of many other factors on female fertility. (C) 2010, Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.”
“Feto-maternal transfusion (FMT) or haemorrhage occurs when there is an entry of fetal blood into the maternal circulation in pregnancy or during delivery. It has been stated that

very small amount of fetal red cells are normally detectable in maternal circulation in all pregnancies. However, massive FMT is rare and even rarer is the resultant severe anaemia which may cause severe fetal morbidity or early neonatal click here death in apparently uneventful normal pregnancy. Massive FMT is regarded as a pathological condition with a variety of clinical presentations essentially secondary to the fetal anaemia. We present a case of FMT associated with umbilical vein dilation and speculate whether this finding is of prognostic value.”
“Metabolic syndrome

(MetS) is defined as a cluster of risk factors for type 2 diabetes and cardiovascular disease; it is also an independent risk factor for developing chronic kidney disease (CKD) in the general population. Therefore, CKD has many similarities and associations with MetS, and the individual risk factors constituting MetS-especially insulin resistance and glucose intolerance, hypertension, dyslipidemia, and obesity-are also common features of the early stages of CKD. In the later stages of CKD, uremia per se and uremic complications such as fluid retention, protein-energy wasting, inflammation, and oxidative stress further contribute to an increase in the prevalence of MetS in CKD patients. In addition, PD patients exposed to glucose-based PD fluids have an increased risk of developing metabolic complications.

Notably, at y = 7 8, only the D0(3) phase (the equilibrium phase

Notably, at y = 7.8, only the D0(3) phase (the equilibrium phase of Fe-Ge at e/a = 1.54) was found in the ternary alloy. The theory also shows that the D0(3) instability is removed for compositions with y >= 3.9, when D0(3) becomes the structure’s ground-state phase. Thus, the high, positive lambda(gamma,2) value for Fe-Ga at

x = 28 could be the result of the high sensitivity of its metastable D0(3) structure. VC 2011 American Institute of Physics. [doi:10.1063/1.3535444]“
“Introduction: We investigated whether primary prevention implantable check details cardioverter defibrillator (ICD) patients with atrial arrhythmias are at higher risk for ICD shocks and mortality compared to patients without atrial arrhythmias in a subanalysis of the PREPARE study.

Methods and Results: Details of the PREPARE study design and results have been previously reported. We now Oncodazole included 537 of the 700 patients enrolled in PREPARE. These patients had a dual or biventricular device and at least one device follow-up after implantation. Continuously collected device diagnostics data were used to classify patients into two groups during follow-up: with (n = 133) or without (n = 404) atrial tachycardia/atrial fibrillation (AT/AF). The primary outcomes were ICD shocks and mortality. Subjects were followed for a mean of 333 +/- 73 (range 5-365) days. During a follow-up of 1 year, ICD shocks

occurred in 44 (8%) patients. Significantly, more patients with AT/AF received a shock (13.0% vs 6.9%, P = 0.03), with inappropriate shocks accounting for the majority of the difference (6.9% vs 2.6%, P = 0.02). There was no difference in prevalence of shocks between patients with and without a history of AF. Mortality was similar in patients with and

without AT/AF, whether detected during the study or prior to the study. In addition, the 34 CHIR-99021 datasheet subjects with high average ventricular rate (>= 110 beats per minute) during AT/AF had a higher risk of an inappropriate shock (21.0% vs 2.1%, P < 0.01).

Conclusion: Primary prevention ICD patients with AT/AF are more likely to receive shocks, especially inappropriate shocks. Mortality was not higher in AT/AF patients. (PACE 2011; 34:1070-1079)”
“Human herpesvirus-6 (HHV-6) belongs to the herpesvirus family and is categorized into variant A and B (HHV-6A and HHV-6B). Primary HHV-6 infection in children and its related diseases are almost exclusively caused by HHV-6B and no disease caused by HHV-6A has been identified. The cellular receptor of HHV-6 has been shown to be a human CD46, and its viral ligand is an envelope glycoprotein complex, gH/gL/gQ1/gQ2 in HHV-6A. Furthermore, both cellular and viral lipid rafts play an important role in the HHV-6 entry process, suggesting that HHV-6 may enter its target cells through a lipid raft-associated mechanism.

Interestingly, the precise expression level of Oct4 determines th

Interestingly, the precise expression level of Oct4 determines the fate of embryonic stem cells. Therefore, to control the expression of Oct4 precisely, a variety of regulators function at multiple levels, including transcription, translation of mRNA and post-translational modification. Additionally, in cooperation with Sox2, Nanog and other members of the core transcriptional regulatory circuitry, Oct4 activates both protein-coding genes and noncoding RNAs necessary for pluripotency.

Simultaneously, in association with transcriptional repressive complexes, Oct4 represses another set of targets involved in developmental processes. Importantly, Oct4 can re-establish pluripotency in somatic cells, and proper reprogramming of Oct4 expression is indispensable for deriving genuine induced pluripotent stem cell lines. In the past several years, genome-wide identification of Oct4 target genes and Oct4-centered RO4929097 order protein interactomes has been reported, indicating that Oct4 exerts tight control over pluripotency

regulator expression and protects embryonic stem cells in an undifferentiated state. Nevertheless, further investigation is required to fully elucidate the underlying molecular mechanisms through which Oct4 maintains and reinitiates pluripotency. Systemic and dynamic exploration of the protein complexes and target genes associated with Oct4 will help to elucidate the role of Oct4 more comprehensively.”

(GSH) and ascorbate SN-38 in vitro (ASC) are important antioxidants that are involved in stress defence and cell proliferation of meristematic root cells. In principle, synthesis of ASC and GSH in the roots as well as ASC and GSH transport from the shoot to the roots by phloem mass flow is possible. However, it is not yet known whether the ASC and/or the GSH level in roots depends on the supply from the shoot. This was analysed by feeding mature leaves with [C-14]ASC or [S-35]GSH and subsequent detection of the radiolabel in different root AR-13324 fractions. Quantitative dependency of root ASC and GSH on shoot-derived ASC and GSH was investigated with poplar (Populus tremulaxP. alba) trees interrupted in phloem transport. [S-35]GSH is transported from mature leaves to the root tips, but is withdrawn from the phloem along the entire transport path. When phloem transport was interrupted, the GSH content in root tips halved within 3 d. [C-14]ASC is also transported from mature leaves to the root tips but, in contrast to GSH, ASC is not removed from the phloem along the transport path. Accordingly, ASC accumulates in root tips. Interruption of phloem transport disturbed the level and the ASC redox state within the entire root system. Diminished total ASC levels were attributed mainly to a decline of dehydroascorbate (DHA).

When the preformed thermoplastic particle,, were mixed with the r

When the preformed thermoplastic particle,, were mixed with the reactive constituents of the epoxy system Under certain curing conditions in which total miscibility was avoided, uniform particle dispersions could be. obtained. The relationships between the composition, morphology (nano-scale and microscale), glass-transition temperature, mechanical properties, and fracture toughness were considered. Four main results were

obtained for consideration of the potential of silica-filled PMMA as an important modifier of brittle epoxy thermoset systems: (1) a good dispersion of the silica nanoparticles in the PMMA domains, (2) a good dispersion of the silica-filled PMMA microparticles in the epoxy matrix, (3) the possibility of partial dissolution of the PMMA-rich domains into the epoxy system, and (4) a slight increase in properties such as the hardness, indentation modulus, and fracture toughness. (c) 2008 Wiley VX-680 in vitro Periodical, Inc. J Appl Polym Sci 111: 2062-2070, 2009″
“The culture fluid of the fungus Fusarium sambucinum

was investigated for the presence of new peptide-containing PP2 price bioregulators, previously identified in various mammalian and plant tissues. A fraction containing peptides with molecular weights from 1000 to 2000 Da, which exhibited specific membranotropic activity and a number of physical and chemical properties buy BYL719 characteristic of this group of bioregulators, was obtained. The effects of this fraction on the model roller organotypic cultivation of liver tissue of the Pleurodeles waltl newt in vitro

were investigated for the first time. This fraction caused the additional activation of pigmented liver cells of newt (analogues to Kupffer cells of the liver of mammals) and provided the maintenance of cell-cell adhesive interactions in tissues. The results show that a new group of peptide bioregulators was present in the culture medium of the fungus F. sambucinum.”
“Background: The Iowa Gambling task, which typically incorporates hypothetical monetary earnings and losses for performance, has been widely used to measure decision-making in substance abusers. We examined the effects of a cash monetary contingency oil Gambling task performance in cocaine abusers and control participants.

Methods: Twenty-two long-term cocaine snickers who met DSM-IV criteria for cocaine dependence and 24 non-cocaine-using Control participants completed this Study. Both groups were similar in terms of age, executive function, and self-reported alcohol and marijuana Use. All participants performed the Gambling task under two Counterbalanced conditions: under one condition, earnings and losses were hypothetical, and under the other condition, earnings and losses were in cash.

Results: Condition x group interactions oil card selection and task completion time were noted (p < 0.05).

Several studies already demonstrated the participation of NO with

Several studies already demonstrated the participation of NO with microbicidal and microbiostatic activity in giardiasis. On the other hand, some works report that Giardia spp. inhibit NO production by consuming the intermediate metabolite arginine. In fact, studies in vitro showed that G. lamblia infection of human intestinal epithelial cells had reduced NO production. This occurs due to limited offer of the crucial substrate arginine (essential aminoacid for NO production), consequently reducing NO production. Therefore, the balance between giardial arginine consumption and epithelial NO production could contribute to the variability of the duration and severity of infections by

this ubiquitous parasite.”
“Human VX-661 inhibitor T-cell leukemia virus type 1 (HTLV-1) infection is endemic in Japan and several countries

in South America, Caribbean and Africa. Endocrine and metabolic disorders have been variably reported to be associated with human T-cell leukemia virus type 1 (HTLV-1) infection. Therefore, the aim of this article was to critically evaluate the current knowledge of the endocrine and metabolic disorders associated with HTLV-1 infection. The literature search used PubMed, Web of Science, and LILACS databases in the past 10 years, utilizing, in various combinations, the following keywords: HTLV-1, adult PI3K inhibitor T-cell leukemia, diabetes mellitus, GLUT-1, osteoporosis, hypercalcemia, autoimmune thyroid disorders, diabetes insipidus, inappropriate antidiuretic hormone secretion; pseudohypoparathyroidism; pseudopseudohypoparathyroidism. Trichostatin A purchase The proven endocrine manifestations of the HTLV-1 infection

are calcium disorders which occur in some patients with acute HTLV-1/Adult T-cell leukemia/lymphoma. The few reports about thyroid, parathyroid, antidiuretic hormone and diabetes mellitus are insufficient to prove a causal association with HTLV-1 infection. The evidence for an association between endocrine disorders and HTLV-1 infection in general, and in asymptomatic patients is lacking. Given all these uncertainties, the endocrine expression of the HTLV-1 infection composes a promising research line for understanding the pathophysiology of this infection.”
“Kikuchi-Fujimoto disease, also known as histiocytic necrotizing lymphadenitis of unknown etiopathogenesis, is a self-limited disease which frequently appears as feverish lymphadenomegaly, thus creating the need for differential diagnosis with lymphoma, systemic lupus erythematosus (SLE), infectious mononucleosis, cat-scratch disease, and toxoplasmosis with lymphonodal impairment. However, there are cases in which it may evolve with complications such as aseptic meningitis, cerebellar ataxia, and aseptic myocarditis. We are presenting a case of a 24-year-old man who had an initial picture of arthralgia, evening fever and adenomegaly.

(C) 2011 American Institute of Physics [doi: 10 1063/1 3607311]“

(C) 2011 American Institute of Physics. [doi: 10.1063/1.3607311]“
“In this article, we report synthesis

and characterization of the self-assembly behavior of coilrod-coil molecules, consisting of four biphenyls and a p-terphenyl unit linked together with ether bonds as a rod segment. These molecules contain lateral methyl or ethoxymethyl groups at 2 and 5 positions of the middle benzene ring of p-terphenyl. The self-assembling behavior of these materials was investigated by means of DSC, POM, and SAXS in the bulk state. The results reveal that self-assembling behavior of these molecules is dramatically influenced by a lateral methyl or ethoxymethyl Selleck Bromosporine groups in the middle of rod segment. In addition, molecule with PEO (DP = 17) coil chains of identical coil volume fraction to the corresponding molecule connected by PPO (DP = 12) coil chains, shows diverse self-organizing behavior that may result from the parameters of cross-sectional area of coil segment and the steric hindrance at the rod/coil interface. (C) 2011 Wiley Periodicals, Inc. J Appl Polym Sci 123: 1007-1014,

“Amorphous semiconductors and chalcogenide glasses exhibit a high density of localized states in their bandgap as a consequence of structural defects or due to a lack of long https://www.selleckchem.com/products/nu7441.html range order. These defect states have a strong influence on the electronic transport properties. Thus, many theories attribute the “”resistance drift”" or the “”threshold switching”" effects, both observed in amorphous phase change alloys, to defects within the bandgap. The energetic distribution of states within the bandgap can be probed via modulated photocurrent (MPC) experiments that enable a spectroscopy of the relative density of these defect states by varying the modulation frequency at various temperatures T. It is also a common feature that the bandgap decreases with temperature. Nevertheless, the consequences of a shrinking bandgap with increasing temperature have been neglected in the classical analysis of MPC experiments. In this paper,

we propose to add correction terms to the classical MPC energy scaling to take the temperature dependence of the bandgap of the studied material into account to improve the accuracy of the determination of the defect distribution. We illustrate the efficacy of our proposed corrections by applying it to the study of disordered SGC-CBP30 materials such as hydrogenated amorphous silicon a-Si:H, a-GeTe and a-Ge(2)Sb(2)Te(5). (C) 2011 American Institute of Physics. [doi:10.1063/1.3605517]“
“This study concerns the synthesis of novel multi block polyurethane (PU) copolymers containing eco-friendly segments, taking the advantage of ionic liquids (IL)s under microwave irradiation. For this, L-leucine anhydride cyclodipeptide (LAC) was prepared and then a new class of poly(ether-urethane-urea) s (PEUUs) was synthesized with two types of ILs, including room temperature imidazolium (RTIL)s and molten ammonium type ILs.

All patients undergoing PD at the time of surgery were included i

All patients undergoing PD at the time of surgery were included in our analysis. Two HD patients matched for age,

diabetes status, and Charleston comorbidity score were obtained for each PD patient.

Results: The analysis included 36 PD patients and 72 HD patients. Mean age, sex, diabetes status, cardiac unit stay, hospital stay, and operative mortality did not differ by dialysis modality. The incidence of 1 or more postoperative complications (infection, prolonged intubation, death) was higher for HD patients click here (50% vs. 28% for PD patients, p = 0.046). After surgery, 2 PD patients required conversion to HD. The 2-year survival was 69% for PD patients and 66% for HD patients (p = 0.73).

Conclusions: Our findings suggest that, compared with HD patients, PD patients who require cardiac surgery do not experience more early complications or a lesser 2-year survival and that 2-year survival for dialysis patients after cardiac surgery is acceptable.”
“Increased coagulation factor levels have been demonstrated to be a risk factor for venous thromboembolism Tariquidar datasheet in patients of Caucasian origin. Coagulation factors, hereditary

thrombophilia, and ABO blood group were evaluated for venous thrombosis risk in a heterogeneous Brazilian Population consisting of 122 women and 53 men, with a median age of 36 years (range 13-63), matched to a control group by age, sex, and ethnicity Increased levels of factor VIII (odds ratio [OR], 3.1; 95% confidence interval [CI], 1.6-6.0), von Willebrand factor (OR, 2.8; 95% CI, 1.4-5.4), non-O blood group (OR, 2.1; 95% CI, 1.3-3.4), and thrombophilia (OR, 3.4; 95% CI, 1.6-7.1) emerged as independent risk factors for venous thromboembolism. The interaction of high levels of factor IX and factor XI with other independent variables increased the potential for thrombosis synergistically. Therefore, the ability of identifying underlying thrombophilia risk factors in our population was enhanced by the inclusion of these factors in the

prothrombotic laboratory workup.”
“Background: Intermittent peritoneal dialysis (IPD) is an old strategy that has generally been eclipsed, in the home setting, Selleck eFT508 by daily peritoneal therapies. However, for a select group of patients with exhausted vascular access or inability to receive PD at home, in-center IPD may remain an option or may serve as an incremental strategy before initiation of full-dose PD. We investigated the residual kidney clearance requirements necessary to allow thrice-weekly IPD regimens to meet current adequacy targets.

Methods: The 3-pore model of peritoneal transport was used to examine 2 thrice-weekly IPD dialysis modalities: 5 – 6 dwells with 10 – 12 L total volume (low-dose IPD), and 50% tidal with 20 – 24 L total volume (high-dose IPD). We assumed an 8-hour dialysis duration and 1.

WIREs Syst Biol Med 2013, 5:307342 doi: 10 1002/wsbm 1212

WIREs Syst Biol Med 2013, 5:307342. doi: 10.1002/wsbm.1212

For further resources related to this article, please visit the WIREs website.”
“A five and a half year-old girl presented with a reddish-brown plaque on her right anterior tibia, first observed 1 year previously and without any history of injury or insect bite. Histological examination showed a dense dermal infiltrate composed of plasma cells and small lymphocytes, combined with lymphocytic exocytosis in the epidermis and interface dermatitis. In addition, a second biopsy found small epithelioid granulomas within the lymphoplasmocytic infiltrate. Infection was ruled out. No clonality was found. None of the treatments attempted PD0325901 ic50 was successful (antibiotics and steroids), and the lesion was stable but did not improve for 4 years. The

same features typical of lymphoplasmocytic pseudolymphoma were observed on a third biopsy. Cyclosporin A A diagnosis of “”pretibial lymphoplasmocytic plaque”" was made on the basis of clinical and histological findings. Recently, 3 other cases of this type of lymphocytic and plasma cell cutaneous infiltrate with very distinctive clinical and histopathological features have been reported in children. Our case is instructive because it presents new and as yet undocumented histopathologic features including a lichenoid reaction with vacuolization of the basal cell layer and numerous apoptotic bodies, apparent in 2 of the 3 biopsies, and hypervascularity with thick-walled blood vessels lined check details with plump endothelial cells in the upper dermis. The clinicopathological presentation of these cases, including ours, is homogenous suggesting a specific entity

described as “”pretibial lymphoplasmocytic plaque in children”". This seems to be a benign, chronic, reactive process, probably arising secondary to a local response to an unknown antigen.”
“We demonstrate that surface acoustic waves (SAWs), nanometer amplitude Rayleigh waves driven at megahertz order frequencies propagating on the surface of a piezoelectric substrate, offer a powerful method for driving a host of extremely fast microfluidic actuation and micro/bioparticle manipulation schemes. We show that sessile drops can be translated rapidly on planar substrates or fluid can be pumped through microchannels at 1-10 cm/s velocities, which are typically one to two orders quicker than that afforded by current microfluidic technologies. Through symmetry-breaking, azimuthal recirculation can be induced within the drop to drive strong inertial microcentrifugation for micromixing and particle concentration or separation. Similar micromixing strategies can be induced in the same microchannel in which fluid is pumped with the SAW by merely changing the SAW frequency to rapidly switch the uniform through-flow into a chaotic oscillatory flow by exploiting superpositioning of the irradiated sound waves from the sidewalls of the microchannel.

In a second test, it was also found that visual duration threshol

In a second test, it was also found that visual duration thresholds were significantly smaller for the early items when participants were asked to name the critical items. These findings support the notion that order-of-acquisition effects can be manifest over a short time span in the laboratory, and that the effect of order of acquisition is

distinct from mere frequency of exposure. The findings are consistent with the idea that AoA effects occurring over a large temporal scale may be a special case of more general order-of-acquisition effects, and both may be a general property of learning mechanisms.”
“The poor performance of autistic individuals on a test of homograph reading is widely interpreted as evidence for a reduction in sensitivity to context termed weak central coherence. To better understand the cognitive processes involved OTX015 in completing FG4592 the homograph-reading task, we monitored

the eye movements of nonautistic adults as they completed the task. Using single trial analysis, we determined that the time between fixating and producing the homograph (eye-to-voice span) increased significantly across the experiment and predicted accuracy of homograph pronunciation, suggesting that participants adapted their reading strategy to minimize pronunciation errors. Additionally, we found evidence for interference from previous trials involving the same homograph. This progressively reduced the initial advantage for dominant homograph pronunciations as the experiment progressed. Our results identify several additional factors that contribute to performance on the homograph reading task and may help to reconcile the findings of poor performance on the test with contradictory findings from other studies using different measures of context sensitivity in autism. The results also undermine some of the broader theoretical inferences that have been drawn from studies of autism using the homograph task. Finally, we suggest that this approach to task deconstruction might have wider applications in experimental psychology.”
“Various surface

featurestimbre, Mizoribine tempo, and pitchinfluence melody recognition memory, but articulation format effects, if any, remain unknown. For the first time, these effects were examined. In Experiment 1, melodies that remained in the same, or appeared in a different but similar, articulation format from study to test were recognized better than were melodies that were presented in a distinct format at test. A similar articulation format adequately induced matching processes to enhance recognition. Experiment 2 revealed that melodies rated as perceptually dissimilar on the basis of the location of the articulation mismatch did not impair recognition performance, suggesting an important boundary condition for articulation format effects on memory recognitionthe matching of the memory trace and recognition probe may depend more on the overall proportion, rather than the temporal location, of the mismatch.