Generalized Limits for Single-Parameter Quantum Estimation

We develop generalized bounds for quantum single-parameter estimation problems for which the coupling to the parameter is described by intrinsic multi-system interactions. For a Hamiltonian with $k$-system parameter-sensitive terms, the quantum limit scales as $1/N^k$ where $N$ is the number of systems. These quantum limits remain valid when the Hamiltonian is augmented by any parameter independent interaction among the systems and when adaptive measurements via parameter-independent coupling to ancillas are allowed.Comment: 4 pages, 1 figure. v2 typos correcte

Amblyopia and quality of life: a systematic review

Background/Aims Amblyopia is a common condition which can affect up to 5% of the general population. The health-related quality of life (HRQoL) implications of amblyopia and/or its treatment have been explored in the literature. Methods A systematic literature search was undertaken (16th-30th January 2007) to identify the HRQoL implications of amblyopia and/or its treatment. Results A total of 25 papers were included in the literature review. The HRQoL implications of amblyopia related specifically to amblyopia treatment, rather than the condition itself. These included the impact upon family life; social interactions; difficulties undertaking daily activities; and feelings and behaviour. The identified studies adopted a number of methodologies. The study populations included; children with the condition; parents of children with amblyopia; and adults who had undertaken amblyopia treatment as a child. Some studies developed their own measures of HRQoL, and others determined HRQoL through proxy measures. Conclusions The reported findings of the HRQoL implications are of importance when considering the management of cases of amblyopia. Further research is required to assess the immediate and long-term effects of amblyopia and/or its treatment upon HRQoL using a more standardised approach

Refinement of the Child Amblyopia Treatment Questionnaire (CAT-QoL) using Rasch analysis

Aims or Purpose: The Child Amblyopia Treatment Questionnaire (CAT-QoL) was developed using a "bottom-up" methodological approach. Interviews with children with amblyopia identified items (questions) and response levels to be tested in a draft questionnaire consisting of 11 items (sad, feeling on face, hurt, doing schoolwork, cross, how other children treat you, doing things, worried, upset with family, playing with friends, happy). This study describes the refinement of the descriptive system for the CAT-QoL instrument using the application of Rasch analysis. METHODS: A multi-centre pilot study was conducted, and data collected from 342 participants. Participants were asked to self-complete the appropriate treatment version of the CAT-QoL questionnaire socio-demographic and clinical data were collected by the clinician using a standardised proforma. A "measure" of child's health was obtained from the parent by asking how they would rate their child's health over the previous week. Rasch analysis techniques were applied to refine the questionnaire. Rasch was used to examine response categories and collapse item response levels, identify poorly performing items, and explore local dependency of items. RESULTS: A total of 331 subjects were included in the study sample, however only 315 were accepted into the RUMM program as a number of subjects had missing questions responses on the CAT-QoL. RUMM also excluded a further 41 subjects as these demonstrated extreme responses. Disordered response categories were found for each item, requiring adjacent response levels to be combined. This was applied to all items, and the model fit was re-examined. Two items were found to have poor fit (cross and happy) and were removed from the measure and the model fit was re-examined. No statistically significant differential item functioning (DIF) was found for any item, using person factors of age, sex or general health. Two items showed some dependency (worried and upset with family), and the poorer fitting item was subsequently removed (upset with family). This resulted in a refined CAT-QoL instrument that consists of 8-items, each with three-level response scales. CONCLUSION: The refined CAT-QoL instrument includes the following items: sad, feeling on face, hurt, doing work at school, how other children treat you, doing things, worried and playing with friends. The CAT-QoL can be Rasch scored, with a range of 0-16 where a greater value indicates a worse quality of life (or greater impact of treatment on the individual). The CAT-QoL may be useful in determining how amblyopia treatment affects children, and offers an alternative to generic patient reported outcome measures

Gender-dependent differences in plasma matrix metalloproteinase-8 elevated in pulmonary tuberculosis.

Tuberculosis (TB) remains a global health pandemic and greater understanding of underlying pathogenesis is required to develop novel therapeutic and diagnostic approaches. Matrix metalloproteinases (MMPs) are emerging as key effectors of tissue destruction in TB but have not been comprehensively studied in plasma, nor have gender differences been investigated. We measured the plasma concentrations of MMPs in a carefully characterised, prospectively recruited clinical cohort of 380 individuals. The collagenases, MMP-1 and MMP-8, were elevated in plasma of patients with pulmonary TB relative to healthy controls, and MMP-7 (matrilysin) and MMP-9 (gelatinase B) were also increased. MMP-8 was TB-specific (p<0.001), not being elevated in symptomatic controls (symptoms suspicious of TB but active disease excluded). Plasma MMP-8 concentrations inversely correlated with body mass index. Plasma MMP-8 concentration was 1.51-fold higher in males than females with TB (p<0.05) and this difference was not due to greater disease severity in men. Gender-specific analysis of MMPs demonstrated consistent increase in MMP-1 and -8 in TB, but MMP-8 was a better discriminator for TB in men. Plasma collagenases are elevated in pulmonary TB and differ between men and women. Gender must be considered in investigation of TB immunopathology and development of novel diagnostic markers

Comparative genomics between Trichomonas tenax and Trichomonas vaginalis: CAZymes and candidate virulence factors

Introduction: The oral trichomonad Trichomonas tenax is increasingly 82 appreciated as a likely contributor to periodontitis, a chronic inflammatory 83 disease induced by dysbiotic microbiota, in humans and domestic animals and 84 is strongly associated with its worst prognosis. Our current understanding of 85 the molecular basis of T. tenax interactions with host cells and the microbiota 86 of the oral cavity are still rather limited. One laboratory strain of T. tenax (Hs- 87 4:NIH/ATCC 30207) can be grown axenically and two draft genome assemblies 88 have been published for that strain, although the structural and functional 89 annotation of these genomes is not available. 90Methods: GenSAS and Galaxy were used to annotate two publicly available 91 draft genomes for T. tenax, with a focus on protein-coding genes. A custom 92 pipeline was used to annotate the CAZymes for T. tenax and the human 93 sexually transmitted parasite Trichomonas vaginalis, the most well-characterized 94 trichomonad. A combination of bioinformatics analyses was used to screen for 95 homologs of T. vaginalis virulence and colonization factors within the T. tenax 96 annotated proteins. 97Results: Our annotation of the two T. tenax draft genome sequences and their 98 comparison with T. vaginalis proteins provide evidence for several candidate 99 virulence factors. These include candidate surface proteins, secreted proteins 100 and enzymes mediating potential interactions with host cells and/or members 101 of the oral microbiota. The CAZymes annotation identified a broad range of 102 glycoside hydrolase (GH) families, with the majority of these being shared 103between the two Trichomonas species. 104 105 Discussion: The presence of candidate T. tenax virulence genes supports the 106hypothesis that this species is associated with periodontitis through direct and 107 indirect mechanisms. Notably, several GH proteins could represent potential new 108 virulence factors for both Trichomonas species. These data support a model 109 where T. tenax interactions with host cells and members of the oral microbiota 110 could synergistically contribute to the damaging inflammation characteristic of 111 periodontitis, supporting a causal link between T. tenax and periodontitis

High resolution imaging reveals heterogeneity in chromatin states between cells that is not inherited through cell division

BACKGROUND: Genomes of eukaryotes exist as chromatin, and it is known that different chromatin states can influence gene regulation. Chromatin is not a static structure, but is known to be dynamic and vary between cells. In order to monitor the organisation of chromatin in live cells we have engineered fluorescent fusion proteins which recognize specific operator sequences to tag pairs of syntenic gene loci. The separation of these loci was then tracked in three dimensions over time using fluorescence microscopy. RESULTS: We established a work flow for measuring the distance between two fluorescently tagged, syntenic gene loci with a mean measurement error of 63 nm. In general, physical separation was observed to increase with increasing genomic separations. However, the extent to which chromatin is compressed varies for different genomic regions. No correlation was observed between compaction and the distribution of chromatin markers from genomic datasets or with contacts identified using capture based approaches. Variation in spatial separation was also observed within cells over time and between cells. Differences in the conformation of individual loci can persist for minutes in individual cells. Separation of reporter loci was found to be similar in related and unrelated daughter cell pairs. CONCLUSIONS: The directly observed physical separation of reporter loci in live cells is highly dynamic both over time and from cell to cell. However, consistent differences in separation are observed over some chromosomal regions that do not correlate with factors known to influence chromatin states. We conclude that as yet unidentified parameters influence chromatin configuration. We also find that while heterogeneity in chromatin states can be maintained for minutes between cells, it is not inherited through cell division. This may contribute to cell-to-cell transcriptional heterogeneity. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12860-016-0111-y) contains supplementary material, which is available to authorized users

A narrative review on the similarities and dissimilarities between myalgic encephalomyelitis/chronic fatigue syndrome (me/cfs) and sickness behavior

It is of importance whether myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a variant of sickness behavior. The latter is induced by acute infections/injury being principally mediated through proinflammatory cytokines. Sickness is a beneficial behavioral response that serves to enhance recovery, conserves energy and plays a role in the resolution of inflammation. There are behavioral/symptomatic similarities (for example, fatigue, malaise, hyperalgesia) and dissimilarities (gastrointestinal symptoms, anorexia and weight loss) between sickness and ME/CFS. While sickness is an adaptive response induced by proinflammatory cytokines, ME/CFS is a chronic, disabling disorder, where the pathophysiology is related to activation of immunoinflammatory and oxidative pathways and autoimmune responses. While sickness behavior is a state of energy conservation, which plays a role in combating pathogens, ME/CFS is a chronic disease underpinned by a state of energy depletion. While sickness is an acute response to infection/injury, the trigger factors in ME/CFS are less well defined and encompass acute and chronic infections, as well as inflammatory or autoimmune diseases. It is concluded that sickness behavior and ME/CFS are two different conditions

Recombinant α-actinin subunit antigens of Trichomonas vaginalis as potential vaccine candidates in protecting against trichomoniasis

BACKGROUND: Human trichomoniasis caused by Trichomonas vaginalis is one of the most common sexually transmitted diseases with more than 200 million cases worldwide. It has caused a series of health problems to patients. For prevention and control of infectious diseases, vaccines are usually considered as one of the most cost-efficient tools. However, until now, work on the development of T. vaginalis vaccines is still mainly focused on the screening of potential immunogens. Alpha-actinin characterized by high immunogenicity in T. vaginalis was suggested as a promising candidate. Therefore, the purpose of this study was to evaluate the protective potency of recombinant α-actinin against T. vaginalis infection in a mouse intraperitoneal model. METHODS: Two selected coding regions of α-actinin (ACT-F, 14-469 aa and ACT-T, 462-844 aa) amplified from cDNA were cloned into pET-32a (+) expression vector and transfected into BL21 cells. After induction with IPTG and purification with electroelution, the two recombinant fusion proteins were emulsified in Freund's adjuvant (FA) and used to immunize BALB/C mice. Following intraperitoneal inoculation with T. vaginalis, the survival rate of mice was monitored for the assessment of protective potency. After immunization, the antibody level in mouse serum was assessed by ELISA, splenocyte proliferation response was detected with CCK8 and cytokines in the supernatant of splenocytes were quantified with a cytometric bead-based assay. RESULTS: We successfully obtained purified ACT-F (70.33 kDa) and ACT-T (61.7kDa). Both recombinant proteins could provide significant protection against T. vaginalis challenge, especially ACT-T (with 100% protection within one month). Meanwhile, high levels of specific total IgG and subtypes (IgG1 &gt; IgG2a) were detected in sera from the immunized mice. Our results also revealed a statistically significant increase in splenocyte proliferation and related cytokine (IFN-γ, IL-6, IL-17A and IL-10) production after repeated stimulation with the corresponding antigens in vitro. CONCLUSIONS: Immunization with both ACT-F and ACT-T could confer partial to complete protection and trigger strong Th1/Th2 mixed humoral and cellular immune responses in the mouse host. This suggested that recombinant α-actinin subunit antigens may be promising vaccine candidates against trichomoniasis