Local quantum phase transition in YFe2Al10.

A phase transition occurs when correlated regions of a new phase grow to span the system and the fluctuations within the correlated regions become long lived. Here, we present neutron scattering measurements showing that this conventional picture must be replaced in YFe2Al10, a compound that forms naturally very close to a [Formula: see text] quantum phase transition. Fully quantum mechanical fluctuations of localized moments are found to diverge at low energies and temperatures; however, the fluctuating moments are entirely without spatial correlations. Zero temperature order in YFe2Al10 is achieved by an entirely local type of quantum phase transition that may originate with the creation of the moments themselves.

Quantum critical fluctuations in layered YFe2Al10.

The absence of thermal fluctuations at T = 0 makes it possible to observe the inherently quantum mechanical nature of systems where the competition among correlations leads to different types of collective ground states. Our high precision measurements of the magnetic susceptibility, specific heat, and electrical resistivity in the layered compound YFe2Al10 demonstrate robust field-temperature scaling, evidence that this system is naturally poised without tuning on the verge of ferromagnetic order that occurs exactly at T = 0, where magnetic fields drive the system away from this quantum critical point and restore normal metallic behavior.

Long-term psychosocial and behavioral adjustment in individuals receiving genetic test results in Lynch syndrome.

A cross-sectional study of 155 participants who underwent genetic testing for Lynch syndrome (LS) examined long-term psychosocial and behavioral outcomes. Participants completed standardized measures of perceived risk, psychosocial functioning, knowledge, and a questionnaire of screening activities. Participants were on average 47.3 years and had undergone testing a mean of 5.5 years prior. Eighty four (54%) tested positive for a LS mutation and 71 (46%) negative. For unaffected carriers, perceived lifetime risk of colorectal cancer was 68%, and surprisingly, 40% among those testing negative. Most individuals demonstrated normative levels of psychosocial functioning. However, 25% of those testing negative had moderate depressive symptoms, as measured by the Center for Epidemiologic Studies for Depression Scale, and 31% elevated state anxiety on the State-Trait Anxiety Inventory. Being female and a stronger escape - avoidant coping style were predictive of depressive symptoms. For state anxiety, similar patterns were observed. Quality of life and social support were significantly associated with lower anxiety. Carriers maintained higher knowledge compared to those testing negative, and were more engaged in screening. In summary, most individuals adapt to genetic test results over the long term and continue to engage in screening. A subgroup, including some non-carriers, may require added psychosocial support.

From antiferromagnetic insulator to correlated metal in pressurized and doped LaMnPO.

Widespread adoption of superconducting technologies awaits the discovery of new materials with enhanced properties, especially higher superconducting transition temperatures T(c). The unexpected discovery of high T(c) superconductivity in cuprates suggests that the highest T(c)s occur when pressure or doping transform the localized and moment-bearing electrons in antiferromagnetic insulators into itinerant carriers in a metal, where magnetism is preserved in the form of strong correlations. The absence of this transition in Fe-based superconductors may limit their T(c)s, but even larger T(c)s may be possible in their isostructural Mn analogs, which are antiferromagnetic insulators like the cuprates. It is generally believed that prohibitively large pressures would be required to suppress the effects of the strong Hund's rule coupling in these Mn-based compounds, collapsing the insulating gap and enabling superconductivity. Indeed, no Mn-based compounds are known to be superconductors. The electronic structure calculations and X-ray diffraction measurements presented here challenge these long held beliefs, finding that only modest pressures are required to transform LaMnPO, isostructural to superconducting host LaFeAsO, from an antiferromagnetic insulator to a metallic antiferromagnet, where the Mn moment vanishes in a second pressure-driven transition. Proximity to these charge and moment delocalization transitions in LaMnPO results in a highly correlated metallic state, the familiar breeding ground of superconductivity.

Size-dependent vibronic coupling in α-Fe2O3.

We report the discovery of finite length scale effects on vibronic coupling in nanoscale α-Fe2O3 as measured by the behavior of vibronically activated d-d on-site excitations of Fe(3+) as a function of size and shape. An oscillator strength analysis reveals that the frequency of the coupled symmetry-breaking phonon changes with size, a crossover that we analyze in terms of increasing three-dimensional character to the displacement pattern. These findings demonstrate the flexibility of mixing processes in confined systems and suggest a strategy for both enhancing and controlling charge-lattice interactions in other materials.

Biallelic EPCAM deletions induce tissue-specific DNA repair deficiency and cancer predisposition.

We report a case of Mismatch Repair Deficiency (MMRD) caused by germline homozygous EPCAM deletion leading to tissue-specific loss of MSH2. Through the use of patient-derived cells and organoid technologies, we performed stepwise in vitro differentiation of colonic and brain organoids from reprogrammed EPCAMdel iPSC derived from patient fibroblasts. Differentiation of iPSC to epithelial-colonic organoids exhibited continuous increased EPCAM expression and hypermethylation of the MSH2 promoter. This was associated with loss of MSH2 expression, increased mutational burden, MMRD signatures and MS-indel accumulation, the hallmarks of MMRD. In contrast, maturation into brain organoids and examination of blood and fibroblasts failed to show similar processes, preserving MMR proficiency. The combined use of iPSC, organoid technologies and functional genomics analyses highlights the potential of cutting-edge cellular and molecular analysis techniques to define processes controlling tumorigenesis and uncovers a new paradigm of tissue-specific MMRD, which affects the clinical management of these patients.

Spin liquids and antiferromagnetic order in the Shastry-Sutherland-lattice compound Yb2Pt2Pb.

We present measurements of the magnetic susceptibility χ and the magnetization M of single crystals of metallic Yb(2)Pt(2)Pb, where localized Yb moments lie on the dimerized and frustrated Shastry-Sutherland lattice (SSL). Strong magnetic frustration is found in this quasi-two-dimensional system, which orders antiferromagnetically at T(N) = 2.02 K from a paramagnetic liquid of Yb dimers, having a gap Δ = 4.6 K between the singlet ground state and the triplet excited states. Magnetic fields suppress the antiferromagnetic (AF) order, which vanishes at a 1.23 T quantum critical point. The spin gap Δ persists to 1.5 T, indicating that dimer singlets survive the collapse of the B = 0 AF state. Quantized steps are observed in M(B) within the AF state, a signature of SSL systems. Our results show that Yb(2) Pt(2)Pb is unique, both as a metallic SSL system that is close to an AF quantum critical point, and as a heavy fermion compound where quantum frustration plays a decisive role.

Hereditary colorectal cancer registries in Canada: report from the Colorectal Cancer Association of Canada consensus meeting; Montreal, Quebec; October 28, 2011.

At a consensus meeting held in Montreal, October 28, 2011, a multidisciplinary group of Canadian experts in the fields of genetics, gastroenterology, surgery, oncology, pathology, and health care services participated in presentation and discussion sessions for the purpose of developing consensus statements pertaining to the development and maintenance of hereditary colorectal cancer registries in Canada. Five statements were approved by all participants.

Development and validation of an instrument to measure the impact of genetic testing on self-concept in Lynch syndrome.

A positive genetic test result may impact on a person's self-concept and affect quality of life. The purpose of the study was to develop a self-concept scale to measure such impact for individuals carrying mutations for a heritable colorectal cancer Lynch syndrome (LS). Two distinct phases were involved: Phase 1 generated specific colorectal self-concept candidate scale items from interviews with eight LS carriers and five genetic counselors, which were added to a previously developed self-concept scale for BRCA1/2 mutation carriers, Phase II had 115 LS carriers complete the candidate scale and a battery of validating measures. A 20-item scale was developed with two dimensions identified through factor analysis: stigma/vulnerability and bowel symptom-related anxiety. The scale showed excellent reliability (Cronbach's α = 0.93), good convergent validity by a high correlation with impact of event scale (r(102) = 0.55, p < 0.001) and Rosenberg self-esteem scale (r(108) = -0.59, p < 0.001), and a low correlation with the Fear questionnaire (r(108) = 0.37, p < 0.001). The scale's performance was stable across participant characteristics. This new scale for measuring self-concept has potential to be used as a clinical tool and as a measure for future studies.

Characterization of two Ashkenazi Jewish founder mutations in MSH6 gene causing Lynch syndrome.

Founder mutations are an important cause of Lynch syndrome and facilitate genetic testing in specific ethnic populations. Two putative founder mutations in MSH6 were analyzed in 2685 colorectal cancer (CRC) cases, 337 endometrial cancer (EnCa) cases and 3310 healthy controls of Ashkenazi Jewish (AJ) descent from population-based and hospital-based case­control studies in Israel, Canada and the United States. The carriers were haplotyped and the age of the mutations was estimated. MSH6*c.3984_3987dupGTCA was found in 8/2685 CRC cases, 2/337 EnCa cases, and 1/3310 controls, consistent with a high risk of CRC (odds ratio (OR) = 9.9, 95% confidence interval (CI) = 1.2­78.9, p = 0.0079) and a very high risk of EnCa (OR = 19.6, 95% CI = 1.8­217.2, p = 0.0006). MSH6*c.3959_3962delCAAG was identified in 3/2685 CRC cases, 2/337 EnCa cases and no controls. Each mutation was observed on separate conserved haplotypes. MSH6*c.3984_3987dupGTCA and MSH6*c.3959_3962delCAAG probably arose around 585 CE and 685 CE, respectively. No carriers were identified in Sephardi Jews (450 cases and 490 controls). Truncating mutations MSH6*c.3984_3987dupGTCA and MSH6*c.3959_3962delCAAG cause Lynch syndrome and are founder mutations in Ashkenazi Jews. Together with other AJ founder mutations, they contribute substantially to the incidence of CRC and EnCa and are important tools for the early diagnosis and appropriate management of AJ Lynch syndrome patients.

Water-dispersible, multifunctional, magnetic, luminescent silica-encapsulated composite nanotubes.

A multifunctional one-dimensional nanostructure incorporating both CdSe quantum dots (QDs) and Fe(3)O(4) nanoparticles (NPs) within a SiO(2)-nanotube matrix is successfully synthesized based on the self-assembly of preformed functional NPs, allowing for control over the size and amount of NPs contained within the composite nanostructures. This specific nanostructure is distinctive because both the favorable photoluminescent and magnetic properties of QD and NP building blocks are incorporated and retained within the final silica-based composite, thus rendering it susceptible to both magnetic guidance and optical tracking. Moreover, the resulting hydrophilic nanocomposites are found to easily enter into the interiors of HeLa cells without damage, thereby highlighting their capability not only as fluorescent probes but also as possible drug-delivery vehicles of interest in nanobiotechnology.

Correlations and incipient antiferromagnetic order within the linear Mn chains of metallic Ti4MnBi2.

We report measurements on Ti4MnBi2, where a crystal structure involving linear chains of Mn ions suggests one-dimensional magnetic character. The electrical resistivity is metallic, consistent with the results of electronic-structure calculations that find a robust Fermi surface albeit with moderate electronic correlations. A Curie-Weiss fit to the magnetic susceptibility suggests that the Mn moments are in the low-spin S = 1/2 configuration. Neutron diffraction measurements detect weak antiferromagnetic order within the Mn chains, with further evidence for the small staggered moment coming from the entropy associated with the ordering peak in the specific heat as well as from the results of spin-polarized electronic-structure calculations. The antiferromagnetic moments are apparently associated with the d x 2 - y 2 and d xy orbitals of Mn while the remaining Mn orbitals are delocalized and nonmagnetic. Strong quantum fluctuations, possibly related to an electronic instability that forms the Mn moment or to the one-dimensional character of Ti4MnBi2, nearly overcome magnetic order.

Germline variants and phenotypic spectrum in a Canadian cohort of individuals with diffuse gastric cancer.

Background: CDH1 pathogenic variants (pvs) cause most cases of inherited diffuse gastric cancer (dgc), but have low detection rates and vary geographically. In the present study, we examined hereditary causes of dgc in patients in Ontario. Methods: CDH1 testing through single-site or multi-gene panels was conducted for patients with dgc meeting the 2015 International Gastric Cancer Linkage Consortium (igclc) criteria, or with isolated dgc at less than 50 years of age, or with a strong family history of cancer identified at the Zane Cohen Centre (zcc). All CDH1-positive patients at zcc, regardless of cancer history, were summarized. Results: In 15 of 85 patients with dgc (17.6%), a pv or likely pv was identified through CDH1 single-site (n = 43) or multi-gene panel (n = 42) testing. The detection rate was 9.4% overall (8 of 85) and 11% using igclc criteria (7 of 65). No CDH1 pvs were identified in patients with isolated dgc at less than 40 years of age, but 1 pv was identified in a patient with isolated dgc at less than 50 years of age. Multi-gene panels identified 9 pvs (21.4%), including CDH1, STK11, ATM, BRCA2, MLH1, and MSH2. Review of 81 CDH1 carriers identified 10% with dgc (median age: 48 years; range: 38-59 years); 41% were unaffected (median age: 53 years; range: 26-89 years). Observed malignancies other than dgc or lobular breast cancer (lbc) included colorectal, gynecologic, kidney or bladder, prostate, testicular, and ductal breast cancers. Lobular-breast cancer was seen only in 3 families. Conclusions: In Ontario, the detection rate of CDH1 pvs in patients with dgc was low: no pvs were identified in patients with isolated dgc at less than 40 years of age, and 1 was identified in a patient with isolated dgc at less than 50 years of age. Isolated lbc with no dgc was observed in CDH1-positive families, as were pathology-confirmed nondgc or non-lbc malignancies, which had not previously been reported. Given a phenotype that overlaps with other hereditary conditions, multi-gene panels are recommended for all patients with dgc at less than 50 years of age and for those meeting igclc criteria.

Elemental analysis of biological specimens in air with a proton microprobe.

The unique capabilities of the proton microprobe in an atmospheric environment as a biological tool are illustrated in studies of arsenic and mercury distributions in siingle strands of hair from poisoning victims and of the distributions of several abundant elements in frozen hydrated eye and kidney specimens from rats.

Serologic evidence of chlamydial and mycoplasmal pharyngitis in adults.

In a study of 763 adult patients we found serologic evidence of infection (a fourfold increase in antibodies) with Chlamydia trachomatis in 20.5 percent of the patients and with Mycoplasma pneumoniae in 10.6 percent, but with group A streptococcus (by culture) in only 9.1 percent. Pharyngitis, the most common problem for which patients seek medical care in the United States, may be caused by nonviral, potentially treatable organisms more often than had been suspected.

Spinon confinement and a sharp longitudinal mode in Yb2Pt2Pb in magnetic fields.

The fundamental excitations in an antiferromagnetic chain of spins-1/2 are spinons, de-confined fractional quasiparticles that when combined in pairs, form a triplet excitation continuum. In an Ising-like spin chain the continuum is gapped and the ground state is Néel ordered. Here, we report high resolution neutron scattering experiments, which reveal how a magnetic field closes this gap and drives the spin chains in Yb2Pt2Pb to a critical, disordered Luttinger-liquid state. In Yb2Pt2Pb the effective spins-1/2 describe the dynamics of large, Ising-like Yb magnetic moments, ensuring that the measured excitations are exclusively longitudinal, which we find to be well described by time-dependent density matrix renormalization group calculations. The inter-chain coupling leads to the confinement of spinons, a condensed matter analog of quark confinement in quantum chromodynamics. Insensitive to transverse fluctuations, our measurements show how a gapless, dispersive longitudinal mode arises from confinement and evolves with magnetic order.

Reduction of Raman scattering and fluorescence from anvils in high pressure Raman scattering.

We describe a new design and use of a high pressure anvil cell that significantly reduces the Raman scattering and fluorescence from the anvils in high pressure Raman scattering experiments. The approach is particularly useful in Raman scattering studies of opaque, weakly scattering samples. The effectiveness of the technique is illustrated with measurements of two-magnon Raman scattering in La2CuO4.

Role of video capsule endoscopy in patients with constitutional mismatch repair deficiency (CMMRD) syndrome: report from the International CMMRD Consortium.

BACKGROUND AND STUDY AIMS: Constitutional mismatch repair deficiency (CMMRD) syndrome, also known as biallelic mismatch repair deficiency (BMMRD) syndrome is a rare autosomal-recessive genetic disorder that has a high mortality due to malignancy in childhood and early adulthood. The small bowel phenotype in CMMRD is not well described and surveillance protocols for small bowel cancer have not been well established. This study was conducted to evaluate the usefulness and clinical impact of video capsule endoscopy (VCE) for small bowel surveillance. PATIENTS AND METHODS: We retrospectively reviewed the prospectively maintained International CMMRD Consortium database. Treating physicians were contacted and VCE report data were extracted using a standardized template. RESULTS: Among 58 patients included in the database, 38 VCE reports were collected from 17 patients. Polypoid lesions were first detected on VCE at a median age of 14 years (range: 4 - 17). Of these, 39 % in 7 patients (15/38) showed large polypoid lesions (> 10 mm) or multiple polyps that prompted further investigations. Consequently, three patients were diagnosed with small bowel neoplasia including one patient with adenocarcinoma. Small bowel neoplasia and/or cancer were confirmed histologically in 35 % of the patients (6/17) who had capsule surveillance and the lesions in half of these patients were initially visualized on VCE. Multiple polyps were identified on eight VCEs that were completed on three patients. Ten VCEs (28 %) were incomplete due to slow bowel transit; none required capsule removal. CONCLUSIONS: Small bowel surveillance in patients with CMMRD should be initiated early in life. VCE has the potential to detect polyps; however, small bowel neoplasias are often proximal and can be missed, emphasizing the importance of concurrent surveillance with other modalities. MEETING PRESENTATIONS: Digestive Disease Week 2017 and World Congress of Pediatric Gastroenterology, Hepatology and Nutrition 2016.

Orbital-exchange and fractional quantum number excitations in an f-electron metal, Yb2Pt2Pb.

Exotic quantum states and fractionalized magnetic excitations, such as spinons in one-dimensional chains, are generally expected to occur in 3d transition metal systems with spin 1/2. Our neutron-scattering experiments on the 4f-electron metal Yb2Pt2Pb overturn this conventional wisdom. We observe broad magnetic continuum dispersing in only one direction, which indicates that the underlying elementary excitations are spinons carrying fractional spin-1/2. These spinons are the emergent quantum dynamics of the anisotropic, orbital-dominated Yb moments. Owing to their unusual origin, only longitudinal spin fluctuations are measurable, whereas the transverse excitations such as spin waves are virtually invisible to magnetic neutron scattering. The proliferation of these orbital spinons strips the electrons of their orbital identity, resulting in charge-orbital separation.

Increased uptake and desulphation of heparin by mouse macrophages in the presence of polycations.

Heparin uptake and desulphation by cultured macrophages were investigated. Histones, polyamino-acids, protamine and eosinophil-basic protein stimulated both heparin uptake and desulphation, processes found to be non-related. Poly-L-ornithine and poly-DL-lysine increased the heparin uptake by about 33-fold, and histone produced up to 7.5-fold increase in the desulphation. The same polycations inhibited heparin desulphation by macrophage extracts.