Jeremy MH - Academia.edu (original) (raw)

Papers by Jeremy MH

Molecular Imaging, 2002

The use of anatomical imaging in clinical oncology practice traditionally relies on comparison of... more The use of anatomical imaging in clinical oncology practice traditionally relies on comparison of patient scans acquired before and following completion of therapeutic intervention. Therapeutic success is typically determined from inspection of gross anatomical images to assess changes in tumor size. Imaging could provide significant additional insight into therapeutic impact if a specific parameter or combination of parameters could be identified which reflect tissue changes at the cellular or physiologic level. This would provide an early indicator or treatment response/outcome in an individual patient before completion of therapy. Moreover, response of a tumor to therapeutic intervention may be heterogeneous. The use of imaging could assist in delineating therapeutic-induced spatial heterogeneity within a tumor mass by providing information related to specific regions that are resistant or responsive to treatment. Largely untapped potential resides in exploratory methods such as diffusion MRI, which is a nonvolumetric intravoxel measure of tumor response based upon water molecular mobility. Alterations in water mobility reflect changes in tissue structure at the cellular level. While the clinical utility of diffusion MRI for oncologic practice is still under active investigation, this overview on the use of diffusion MRI for the evaluation of brain tumors will serve to introduce how this approach may be applied in the future for the management of patients with solid tumors.

Recent large-scale mutagenesis screens have made the zebrafish the first vertebrate organism to a... more Recent large-scale mutagenesis screens have made the zebrafish the first vertebrate organism to allow a forward genetic approach to the discovery of developmental control genes 1-3 . Mutations can be cloned positionally, or placed on a simple sequence length polymorphism (SSLP) map 4--6 to match them with mapped candidate genes and expressed sequence tags 7,8 (ESTs). To facilitate the mapping of candidate genes and to increase the density of markers available for positional cloning, we have created a radiation hybrid (RH) map of the zebrafish genome. This technique is based on somatic cell hybrid lines produced by fusion of lethally irradiated cells of the species of interest with a rodent cell line. Random fragments of the donor chromosomes are integrated into recipient chromosomes or retained as separate minichromosomes 9,10 . The radiation-induced breakpoints can be used for mapping in a manner analogous to genetic mapping, but at higher resolution and without a need for polymorphism. Genome-wide maps exist for the human, based on three RH panels of different resolutions 11-13 , as well as for the dog 14 , rat 15 and mouse 16,17 . For our map of the zebrafish genome, we used an existing RH panel 18,19 and 1,451 sequence tagged site (STS) markers, including SSLPs, cloned candidate genes and ESTs. Of these, 1,275 (87.9%) have significant linkage to at least one other marker. The fraction of ESTs with significant linkage, which can be used as an estimate of map coverage, is 81.9%. We found the average marker retention frequency to be 18.4%. One cR 3000 is equivalent to 61 kb, resulting in a potential resolution of approximately 350 kb.

Personality and Individual Differences, 2004

This study examined the component structure of impulsivity, by Principal Components Analysis of 1... more This study examined the component structure of impulsivity, by Principal Components Analysis of 12 subscales, from four widely used self-report measures of impulsivity. Two hundred and forty five subjects from the UK general population completed the Eysenck Impulsiveness ...

Gastroenterology, 2006

Background & Aims: Hyperplastic polyposis syndrome (HPS) is defined phenotypically with multiple,... more Background & Aims: Hyperplastic polyposis syndrome (HPS) is defined phenotypically with multiple, large and/or proximal hyperplastic polyps. There is no known germ-line predisposition. We aimed to characterize the clinicopathologic features of 38 patients with HPS and explore the role of germ-line mutations in the base excision repair genes MBD4 and MYH. Methods: Utilizing clinical databases of The Royal Melbourne Hospital Bowel Cancer Surveillance Service and the Familial Cancer Clinic, 38 patients with HPS were recruited. The patients were analyzed for age at first diagnosis, features of hyperplastic polyposis, family histories of polyposis and colorectal cancer (CRC), coexisting adenomas, serrated adenomas, incidence of CRC, and microsatellite instability in the tumours. Mutation analysis of MBD4 and MYH were performed. Results: Serrated adenomas were common (26%), and 19 (50%) of the 38 patients had a first-degree relative with CRC. Family history of HPS was uncommon, with only 2 cases found. Ten patients developed CRC, and 3 required surgery for polyposis. No pathogenic mutations in MBD4 were detected in the 27 patients tested, but 6 single nucleotide polymorphisms of uncertain functional significance were identified. Pathogenic biallelic MYH mutations were detected in 1 patient. Conclusions: Mutations in MBD4 are unlikely to be implicated in HPS; MYH mutations should be studied, especially when adenomas occur in the same patient. The clinical, histopathologic, and molecular findings of this study should contribute to our understanding of HPS and its relationship to the serrated neoplasia pathway.

Arthritis and Rheumatism, 1987

Monocyte—macrophage polypeptides (monokines) cause synovial cells to increase the levels of putat... more Monocyte—macrophage polypeptides (monokines) cause synovial cells to increase the levels of putative mediators of destruction and inflammation. This interaction may account for some of the properties of rheumatoid pannus. We report here that samples of purified human interleukin-1β(IL-1β) and recombinant IL-1β stimulate both the plasminogen activator activity and prostaglandin E2 levels of human synovial fibroblast-like cells. The same holds true for purified pig IL-1 (catabolin) and recombinant murine IL-1. The elevation in plasminogen activator activity was inhibited by indomethacin, and this suggests that endogenous prostanoids are important in the IL-1-mediated stimulation of proteinase activity.

Archives of Clinical Neuropsychology, 2010

BMC Microbiology, 2009

Background: Wolbachia (wBm) is an obligate endosymbiotic bacterium of Brugia malayi, a parasitic ... more Background: Wolbachia (wBm) is an obligate endosymbiotic bacterium of Brugia malayi, a parasitic filarial nematode of humans and one of the causative agents of lymphatic filariasis. There is a pressing need for new drugs against filarial parasites, such as B. malayi. As wBm is required for B. malayi development and fertility, targeting wBm is a promising approach. However, the lifecycle of neither B. malayi nor wBm can be maintained in vitro. To facilitate selection of potential drug targets we computationally ranked the wBm genome based on confidence that a particular gene is essential for the survival of the bacterium.

Journal of Gay & Lesbian Mental Health, 2012

Although sexual minority (SM) adolescent girls are at high risk for suicidal behavior, little is ... more Although sexual minority (SM) adolescent girls are at high risk for suicidal behavior, little is known about their use of mental health services (MHS). Therefore, we examined survey data from a sample of Boston high school students to compare the prevalence of MHS use among SM and heterosexual girls.We used chi-square tests to assess the statistical significance of group differences. To test whether SM status moderated the association between MHS use and mental health need (i.e., whether the student reported self-harm, suicidal ideation, or a suicide attempt in the past year), we entered mental health need, SM status, and the interaction term of the two into a regression model that predicted past 12-month MHS use.SM girls (n = 89) were significantly more likely than heterosexual girls (n = 800) to report suicidal ideation, suicide attempts, and self-harm. SM girls were also more likely to have reported a past 12-month MHS contact (54% vs. 26%, p < 0.0001); this finding held for those with and without a high level of mental health need. The interaction term was not statistically significant, indicating that SM status does not moderate the effect of mental health need on MHS use. These results indicate that SM girls, particularly those experiencing suicidality, are likely to report a MHS contact. Future research is needed to elucidate when/how SM girls come to use MHS and what types of services they are receiving.

Nature, 2001

sequences that could be aligned to 32,235 HTGS human sequences.� Of these alignments, 83,219 of t... more sequences that could be aligned to 32,235 HTGS human sequences.� Of these alignments, 83,219 of them were from clones contained in the WG BAC map and confirmed or contributed to accessioned sequence placement.� Additional evidence for placement of the sequence came from examining believed sequence overlaps with neighboring sequenced clones.� The believed overlaps were generated by an all-against-all sequence comparison of all accessioned sequences (G. Schuler and J. Kent).� The believed overlaps were ranked as either strong (includes additional supporting data such as paired BAC end linkages) or weak (sequence overlap alone) and were weighted accordingly in this consideration.

Journal of Behavioral Health Services & Research, 2005

Patterns of mental health (MH) and substance abuse (SA) treatment utilization among populations r... more Patterns of mental health (MH) and substance abuse (SA) treatment utilization among populations receiving services through multiple public programs are not well known. This study examines to what extent populations with MH and/or SA conditions utilize treatment services through Medicaid and State MH/SA Agencies. Data are from the Substance Abuse and Mental Health Services Administration Integrated Database, a multiyear file for 3 states combining Medicaid and State MH/SA Agency administrative data into a uniform database. Although populations with co-occurring conditions and those served by both Medicaid and State MH/SA Agencies have substantial contact with the public treatment system, a majority of the MH/SA populations examined here utilize few services over brief periods of time. Utilization is most limited among individuals with MH-only conditions and those served exclusively by Medicaid. While a lack of data on clinical outcomes prevents us from drawing conclusions about the effectiveness of MH/SA services, results of this analysis indicate that public programs in the states examined here do not provide services that are primarily utilized on a frequent or chronic basis.

Using data from the COSMOS survey, we perform the first joint analysis of galaxy-galaxy weak lens... more Using data from the COSMOS survey, we perform the first joint analysis of galaxy-galaxy weak lensing, galaxy spatial clustering, and galaxy number densities. Carefully accounting for sample variance and for scatter between stellar and halo mass, we model all three observables simultaneously using a novel and self-consistent theoretical framework. Our results provide strong constraints on the shape and redshift evolution of the stellar-to-halo mass relation (SHMR) from z=0.2 to z=1. At low stellar mass, we find that halo mass scales as Mh M*^0.46 and that this scaling does not evolve significantly with redshift to z=1. We show that the dark-to-stellar ratio, Mh/M*, varies from low to high masses, reaching a minimum of Mh/M*~27 at M*=4.5x10^10 Msun and Mh=1.2x10^12 Msun. This minimum is important for models of galaxy formation because it marks the mass at which the accumulated stellar growth of the central galaxy has been the most efficient. We describe the SHMR at this minimum in terms of the "pivot stellar mass", M*piv, the "pivot halo mass", Mhpiv, and the "pivot ratio", (Mh/M*)piv. Thanks to a homogeneous analysis of a single data set, we report the first detection of mass downsizing trends for both Mhpiv and M*piv. The pivot stellar mass decreases from M*piv=5.75+-0.13x10^10 Msun at z=0.88 to M*piv=3.55+-0.17x10^10 Msun at z=0.37. Intriguingly, however, the corresponding evolution of Mhpiv leaves the pivot ratio constant with redshift at (Mh/M*)piv~27. We use simple arguments to show how this result raises the possibility that star formation quenching may ultimately depend on Mh/M* and not simply Mh, as is commonly assumed. We show that simple models with such a dependence naturally lead to downsizing in the sites of star formation. Finally, we discuss the implications of our results in the context of popular quenching models, including disk instabilities and AGN feedback.

This report summarizes the final results from the OPAL collaboration on searches for neutral Higg... more This report summarizes the final results from the OPAL collaboration on searches for neutral Higgs bosons predicted by the Minimal Supersymmetric Standard Model (MSSM). CP-conserving and for the first time at LEP CP-violating scenarios are studied. New scenarios are also included, which aim to set the stage for Higgs searches at future colliders. The results are based on the data collected with the OPAL detector at e + e − centre-ofmass energies up to 209 GeV. The data are consistent with the prediction of the Standard Model with no Higgs boson produced. Model-independent limits are derived for the cross-sections of a number of event topologies motivated by predictions of the MSSM. Limits on Higgs boson masses and other MSSM parameters are obtained for a number of representative MSSM benchmark scenarios. For example, in the CP-conserving scenario m h −max where the MSSM parameters are adjusted to predict the largest range of values for m h at each tan β, and for a top quark mass of 174.3 GeV, the domain 0.7 < tan β < 1.9 is excluded at the 95% confidence level and Higgs boson mass limits of m h > 84.5 GeV and m A > 85.0 GeV are obtained. For the CP-violating benchmark scenario CPX which, by construction, enhances the CP-violating effects in the Higgs sector, the domain tan β < 2.8 is excluded but no universal limit can be set on the Higgs boson masses.

Cardiovascular Research, 2010

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since t... more In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.

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Upper limits on the cross-section of the pair-production process e + e − →h 0 A 0 , assuming 100 ... more Upper limits on the cross-section of the pair-production process e + e − →h 0 A 0 , assuming 100 % decays into hadrons, are derived from a new search for the h 0 A 0 → hadrons topology, independent of the hadronic flavour of the decay products. Searches for the neutral Higgs bosons h 0 and A 0 , are used to obtain constraints on the Type II Two Higgs Doublet Model (2HDM(II)) with no CP violation in the Higgs sector and no additional non Standard Model particles besides the five Higgs bosons. The analysis combines LEP1 and LEP2 data collected with the OPAL detector up to the highest available centre-of-mass energies. The searches are sensitive to the h 0 , A 0 →qq, gg, τ + τ − and h 0 →A 0 A 0 decay modes of the Higgs bosons. The 2HDM(II) parameter space is explored in a detailed scan. Large regions of the 2HDM(II) parameter space are excluded at the 95% CL in the (m h , m A ), (m h , tanβ) and (m A , tanβ) planes, using both direct neutral Higgs boson searches and indirect limits derived from Standard Model high precision measurements. The region 1 m h 55 GeV and 3 m A 63 GeV is excluded at 95 % CL independent of the choice of the 2HDM(II) parameters.

Nature, 2011

Multiple sclerosis is a common disease of the central nervous system in which the interplay betwe... more Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis.

Astrophysical Journal, 2005

We examine the dependence of the mass-to-light (M/L) ratio of large-scale structure on cosmologic... more We examine the dependence of the mass-to-light (M/L) ratio of large-scale structure on cosmological parameters, in models that are constrained to match observations of the projected galaxy correlation function wp(rp) and the galaxy luminosity function. For a sequence of cosmological models with a fixed, observationally motivated power spectrum shape and increasing normalization σ8, we find parameters of the galaxy halo occupation distribution (HOD) that reproduce wp(rp) measurements as a function of luminosity from the Sloan Digital Sky Survey (SDSS). From these HOD models we calculate the r-band conditional luminosity function Φ(L|Mh), and from this the mean M/L ratio as a function of halo mass Mh. We also use Φ(L|Mh) to populate halos of N-body simulations with galaxies and thereby compute M/L in a range of large-scale environments, including cluster infall regions. For all cosmological models, the M/L ratio in high-mass halos or high-density regions is approximately independent of halo mass or smoothing scale. However, the ``plateau'' value of M/L depends on σ8 in addition to the obvious proportionality with the matter density parameter Ωm, and it represents the universal value <M/L>=Ωmρcrit/ρlum only for models in which the galaxy correlation function is approximately unbiased, i.e., with σ8~σ8g. Our results for cluster mass halos follow the trend (M/L)cl=577(Ωm/0.3)(σ8/0.9)1.7 h Msolar/Lsolar. Combined with the mean M/L ratio for CNOC galaxy clusters, this relation implies (σ8/0.9)(Ωm/0.3)0.6=0.75+/-0.06. M/L estimates for SDSS clusters and the virial regions of clusters in the CAIRNS survey imply a similar value of σ8Ω0.6m, while the CAIRNS estimates for cluster infall regions imply a lower value. These results are inconsistent with parameter values Ωm~0.3, σ8~0.9 favored by recent joint analyses of cosmic microwave background measurements and other large-scale structure data, although they agree with values inferred from the van den Bosch et al. analysis of the 2dF Galaxy Redshift Survey. We discuss possible resolutions of this discrepancy, none of which seems entirely satisfactory. In appendices we present an improved formula for halo bias factors calibrated on our 3603 N-body simulations and an improved analytic technique for calculating the galaxy correlation function from a given cosmological model and HOD.