A33 shows similar sensitivity to but is more specific than CDX2 as an immunomarker of colorectal carcinoma

Aims: CDX2 is widely used as a sensitive and specific immunomarker for colorectal carcinoma (CRC) but neither this sensitivity nor specificity is absolute. This study is the first known comparison of CDX1 and A33 against CDX2 as immunomarkers for CRC. Methods and Results: As a pilot study, whole sections of 51 cases of liver metastatic carcinoma of different origins - colorectum (n=32), breast (n=3), oesophagogastric tract (n=4), lung (n=3), pancreas (n=8), and prostate (n=1) - were immunostained with CDX1, CDX2 and A33. Compared with CDX1, A33 showed higher sensitivity as a CRC immunomarker, greater interobserver reproducibility for assessment of expression, and less background cross-reactivity. Therefore, only A33 was compared with CDX2 for a tissue microarray-based study of primary adenocarcinomas of different origin: CRC (n=55), liver deposits of metastatic CRC (n=60), breast (n=101), lung (n=40), oesophagogastric tract (n=134), ovary (n= 67), pancreas (n= 77), and prostate (n= 56). Combining the whole section and TMA cases of CRC, A33 had a sensitivity of 95.9% and CDX2 a sensitivity of 97.2%. Combining all the whole section and TMA cases of non-colorectal carcinomas, A33 showed 85.4% specificity as a marker of CRC compared to CDX2 which showed a specificity of 64.3%. The higher specificity of A33 as a colorectal carcinoma immunomarker compared with CDX2 was particularly seen amongst pancreatic and ovarian carcinomas. Further, unlike with CDX2, none of the prostatic and lung carcinomas studied showed A33 positivity. Conclusions: A33 shows similar sensitivity to but is more specific than CDX2 as an immunomarker of CRC

On polynomially integrable domains in Euclidean spaces

Let $D$ be a bounded domain in $\mathbb R^n,$ with smooth boundary. Denote $V_D(\omega,t), \ \omega \in S^{n-1}, t \in \mathbb R,$ the Radon transform of the characteristic function $\chi_{D}$ of the domain $D,$ i.e., the $(n-1)-$ dimensional volume of the intersection $D$ with the hyperplane $\{x \in \mathbb R^n: =t \}.$ If the domain $D$ is an ellipsoid, then the function $V_D$ is algebraic and if, in addition, the dimension $n$ is odd, then $V(\omega,t)$ is a polynomial with respect to $t.$ Whether odd-dimensional ellipsoids are the only bounded smooth domains with such a property? The article is devoted to partial verification and discussion of this question

Potential Models and Lattice Gauge Current-Current Correlators

We compare current-current correlators in lattice gauge calculations with correlators in different potential models, for a pseudoscalar charmonium in the quark-gluon plasma. An important ingredient in the evaluation of the current-current correlator in the potential model is the basic principle that out of the set of continuum states, only resonance states and Gamow states with lifetimes of sufficient magnitudes can propagate as composite objects and can contribute to the current-current correlator. When the contributions from the bound states and continuum states are properly treated, the potential model current-current correlators obtained with the potential proposed in Ref. [11] are consistent with the lattice gauge correlators. The proposed potential model thus gains support to be a useful tool to complement lattice gauge calculations for the study of $Q\bar Q$ states at high temperatures.Comment: 18 pages, 4 figures, to be published in Physcial Review

Detection of antibody-dependent complement mediated inactivation of both autologous and heterologous virus in primary HIV-1 infection

Specific CD8 T-cell responses to human immunodeficiency virus type 1 (HIV-1) are induced in primary infection and make an important contribution to the control of early viral replication. The importance of neutralizing antibodies in containing primary viremia is questioned because they usually arise much later. Nevertheless antienvelope antibodies develop simultaneously with, or even before, peak viremia. We determined whether such antibodies might control viremia by complement-mediated inactivation (CMI). In each of seven patients studied, antibodies capable of CMI appeared at or shortly after the peak in viremia, concomitantly with detection of virus-specific T-cell responses. The CMI was effective on both autologous and heterologous HIV-1 isolates. Activation of the classical pathway and direct viral lysis were at least partly responsible. Since immunoglobulin G (IgG)-antibodies triggered the CMI, specific memory B cells could also be induced by vaccination. Thus, consideration should be given to vaccination strategies that induce IgG antibodies capable of CMI

A systematic review of non-motor symptom evaluation in clinical trials for amyotrophic lateral sclerosis

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is increasingly recognised as a multi-system disorder, presenting with common and impactful non-motor symptoms, such as neuropsychiatric symtpoms, cognitive and behavioural changes, pain, disordered sleep, fatigue and problematic saliva. AIM/HYPOTHESIS: We aimed to systematically review 25 years of ALS clinical trials data to identify if non-motor features were evaluated, in addition to the traditional measures of motor functioning and survival, and where evaluated to describe the instruments used to assess. We hypothesised that assessment of non-motor symptoms has been largely neglected in trial design and not evaluated with ALS-suitable instruments. METHODS: We reviewed clinical trials of investigative medicinal products in ALS, since the licensing of riluzole in 1994. Trial registry databases including WHO International Trials Registry, European Clinical Trials Register, clinicaltrials.gov, and PubMed were systematically searched for Phase II, III or IV trials registered, completed or published between 01/01/1994 and 16/09/2020. No language restrictions were applied. RESULTS: 237 clinical trials, including over 29,222 participants, were investigated for their use of non-motor outcome measures. These trials evaluated neuropsychiatric symptoms (75, 32%), cognitive impairment (16, 6.8%), behavioural change (34, 14%), pain (55, 23%), sleep disturbances (12, 5%) and fatigue (18, 8%). Problematic saliva was assessed as part of composite ALS-FRS(R) scores in 184 trials (78%) but with no focus on this as an isolated symptom. 31 (13%) trials including 3585 participants did not include any assessment of non-motor symptoms. CONCLUSIONS: Non-motor symptoms such as neuropsychiatric, cognitive and behavioural changes, pain, disordered sleep, fatigue, and problematic saliva have not been consistently evaluated in trials for people with ALS. Where evaluated, non-symptoms were primarily assessed using instruments and impairment thresholds that are not adapted for people with ALS. Future trials should include non-motor symptom assessments to evaluate the additional potential therapeutic benefit of candidate drugs. PROPSERO REGISTRATION: CRD42020223648. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00415-021-10651-1

Applications of Skyrme energy-density functional to fusion reactions spanning the fusion barriers

The Skyrme energy density functional has been applied to the study of heavy-ion fusion reactions. The barriers for fusion reactions are calculated by the Skyrme energy density functional with proton and neutron density distributions determined by using restricted density variational (RDV) method within the same energy density functional together with semi-classical approach known as the extended semi-classical Thomas-Fermi method. Based on the fusion barrier obtained, we propose a parametrization of the empirical barrier distribution to take into account the multi-dimensional character of real barrier and then apply it to calculate the fusion excitation functions in terms of barrier penetration concept. A large number of measured fusion excitation functions spanning the fusion barriers can be reproduced well. The competition between suppression and enhancement effects on sub-barrier fusion caused by neutron-shell-closure and excess neutron effects is studied.Comment: 28 pages, 13 figures and 2 tables. accepted by Nucl. Phys.

Demographic trends in the incidence of malignant appendiceal tumours in England between 1995 and 2016:Population-based analysis

AIMS: Recent data suggest that the incidence of malignant appendiceal tumours is increasing. This study aimed to determine temporal trends in the incidence of malignant appendiceal tumours within England and a possible influence by demographic factors. METHODS: All incident cases of appendiceal tumours in patients aged 20 years and above were identified from the National Cancer Registration and Analysis Service database between 1995 and 2016 using ICD-9/10 codes. Cancers were categorized according to histology. Joinpoint regression analysis was used to investigate changes in age-standardized incidence rates by age, sex, histological subtype and index of multiple deprivation quintiles, based on socioeconomic domains (income, employment, education, health, crime, barriers to housing and services and living environment). Average annual per cent changes (AAPCs) were estimated by performing Monte-Carlo permutation analysis. RESULTS: A total of 7333 tumours were diagnosed and 7056 patients were analysed, comprising 3850 (54.6 per cent) neuroendocrine tumours (NETs), 1892 (26.8 per cent) mucinous adenocarcinomas and 1314 (18.6 per cent) adenocarcinoma (not otherwise specified). The overall incidence of appendiceal tumours increased from 0.3 per 100 000 to 1.6 per 100 000 over the study interval. Incidence rate increases of comparable magnitude were observed across all age groups, but the AAPC was highest among patients aged 20–29 years (15.6 per cent, 95 per cent c.i 12.7–18.6 per cent) and 30–39 years (14.2 per cent, 12.2–16.2 per cent) and lowest among those aged 70–79 years (6.8 per cent, 5.7–8.0 per cent). Similar incidence rate increases were reported across all socioeconomic deprivation quintiles and in both sexes. Analysis by grade of NET showed that grade 1 tumours accounted for 63 per cent between 2010 and 2013, compared with 2 per cent between 2000 and 2003. CONCLUSIONS: The incidence rate of malignant appendiceal tumours has increased significantly since 1995 and is mainly attributed to an increase in NETs. The increased diagnosis of low-grade NETs may in part be due to changes in pathological classification systems

Comparison of bird community indices for riparian restoration planning and monitoring

The use of a bird community index that characterizes ecosystem integrity is very attractive to conservation planners and habitat managers, particularly in the absence of any single focal species. In riparian areas of the western USA, several attempts at arriving at a community index signifying a functioning riparian bird community have been made previously, mostly resorting to expert opinions or national conservation rankings for species weights. Because extensive local and regional bird monitoring data were available for Nevada, we were able to develop three different indices that were derived empirically, rather than from expert opinion. We formally examined the use of three species weighting schemes in comparison with simple species richness, using different definitions of riparian species assemblage size, for the purpose of predicting community response to changes in vegetation structure from riparian restoration. For the three indices, species were weighted according to the following criteria: (1) the degree of riparian habitat specialization based on regional data, (2) the relative conservation ranking of landbird species, and (3) the degree to which a species is under-represented compared to the regional species pool for riparian areas. To evaluate the usefulness of these indices for habitat restoration planning and monitoring, we modeled them using habitat variables that are expected to respond to riparian restoration efforts, using data from 64 sampling sites in the Walker River Basin in Nevada and California. We found that none of the species-weighting schemes performed any better as an index for evaluating overall habitat condition than using species richness alone as a community index. Based on our findings, the use of a fairly complete list of 30–35 riparian specialists appears to be the best indicator group for predicting the response of bird communities to the restoration of riparian vegetation