5,655 research outputs found
The oncology wall: Could Ali Baba have got to the nutrition treasure without using the correct words?
No full text[No abstract available
Interview with Kenneth Sprunt
No full textKenneth Sprunt was born in Wilmington in 1920, the third son of James Lawrence Sprunt. The Sprunts have a long history in and around Wilimington. His grandfather was a cotton merchant in the area and his great-great Uncle is the man for whom James Sprunt Community College is named for as well as the author of Chronicles of the Lower Cape Fear. Mr. Kenneth Sprunt relates his family history both before his birth and after. He spent three years in the Coast Guard during WWII primarily working on anti-submarine warfare in small boats
Memorandum from Kenneth Iyeko
No full textMemorandum from Kenneth Iyeko regarding establishment and support of the Japanese American Citizens' League at incarceration camps operated by War Relocation Authority.Personal correspondence, organizational records, government documents, publications, and other papers created or collected by Joseph R. Goodman documenting the forced removal and incarceration of Japanese Americans during World War II, as well as organized resistance to incarceration. Included in the collection are records of the Japanese Young Men's Christian Association and the Japanese American Citizens' League in San Francisco, including papers of the Japanese YMCA's executive secretary Lincoln Kanai; Sakai family papers; Goodman's correspondence to and from Japanese American incarcerees, organizations opposing forced removal and incarceration of Japanese Americans, the War Relocation Authority, and others; publications, photographs, and ephemera from the Topaz Relocation Center, where Goodman taught high school; War Relocation Authority records and publications; and newspaper clippings, pamphlets, and reports about forced removal and incarceration created by various government, religious, and civic organizations, in California and nationwide
A Review by Kenneth Atkinson of Alexandria and Qumran: Back to the Beginning, by Kenneth Silver
No full textKenneth Silver (a.k.a. Kenneth A. K. Lönnqvist), is a historian and professional archaeologist, who has lived and worked for decades in the Near East. With extensive publications on Hellenistic and Roman archaeology, history, and numismatics, Silver is the director of a survey and mapping project in Northern Mesopotamia studying the border zone between the late Roman/ Byzantine Empires and Persia. Author of numerous publications on Qumran and related topics, Silver’s lengthy monograph proposes that the documents and type of library found at Qumran were based on models derived from Egypt. The main thesis of the volume is that Pythagorean philosophy is the core and basis for the beliefs reflected in the non-Biblical texts found at Qumran
Assessment of muscle wasting
No full textCachexia occurs commonly and is a significant cause of morbidity and up to 20% mortality
in patients with cancer. Loss of muscle mass occurs as part of the cachexia wasting process
and low muscle mass is a key element of the most recent consensus cachexia definition.
Measuring muscle mass and changes in skeletal muscle is important to phenotype cachectic
individuals and to monitor response to anti-cachectic treatments. This thesis investigates
minimally invasive or burdensome methods of measuring muscle mass and muscle protein
kinetics for use in a clinical or research setting.
Quantification of muscle area on routine diagnostic cross-sectional imaging offers a novel
and relatively non-invasive method of assessing both regional (and by extrapolation) whole
body muscle mass. The need for such a direct measurement of muscle mass was
demonstrated by showing that simple anthropometric formulae are unable to predict
muscularity accurately (within 25%) when compared with estimates derived from patients
diagnostic CT scans.
It may be that qualitative changes in muscle may be more sensitive indices of the wasting
process rather than qualitative change. Myosteatosis (infiltration of muscle by fat) is known
to occur in both cachexia and age related sarcopenia and can be quantified using the
Hounsfield spectrum observed on routine diagnostic CT scans. However, not all patients
undergo routine CT scanning and there is a need for a biomarker derived from urine or
blood. Consequently, cross sectional imaging was used to phenotype patients in a proteomic
analysis of urine with the aim of identifying protein or peptide biomarkers associated with
myosteatosis in cancer cachexia. A biomarker model for myosteatosis was developed with
good sensitivity (97%) but poor specificity (71%). Many of the potential protein / peptide
markers identified had poor associations with known mechanisms of muscle wasting and
further study of the identified peptides in an extended cohort would help determine the
validity of the present findings. However, two proteins with potential roles in muscle repair
or neuromuscular function (Agarin and Cathepsin C) were identified and these may warrant
targeted investigation with evaluation against sequential measures of muscle mass to
determine their value in defining muscle loss over time.
As different regional measures of muscularity are available, trunk (L3 CT) and limb muscle
(quadriceps MRI) cross sectional measurements were compared with functional assessments
to determine the optimal site for measurement. Neither measure proved superior to the other
but appeared to reflect different aspects of function. Quadriceps muscle area correlated with
quadriceps strength and power whilst truncal muscle area correlated more with complex
movements such as the timed-up-and-go test.
Changes in regional muscle area in patients with upper gastrointestinal cancer were assessed
by upper and lower limb MRI before and after surgery and by L3 CT cross sectional area
before and after neo-adjuvant chemotherapy. No change in limb muscularity was seen at 220
days post operatively compared with pre-op measurements. During neo-adjuvant
chemotherapy a significant loss of truncal muscle occurred in the absence of significant
weight loss suggesting that sequential cross sectional imaging is capable of detecting
changes in body composition that may not be apparent clinically.
Whilst sequential scans may document changes in muscularity, they do not describe the
underlying levels of muscle synthesis or degradation that may regulate muscle volume. The
final section of this thesis describes the development of a novel tracer method to measure
skeletal muscle synthesis and its application in a study of patients with cancer and healthy
volunteers. This novel method was able to measure skeletal muscle fractional synthetic rate
(FSR) over a longer time-period than previous methods (weeks rather than hours) and
reduced the burden on the patient by the use of a single oral tracer dose and single muscle
biopsy. Comparison of synthesis rates in quadriceps and rectus abdominis showed higher
rates in quadriceps, 0.067% per hour vs 0.058% per hour respectively. Despite a net loss of
muscle as measured by serial CT scans, skeletal muscle FSR appeared to be marginally
increased in weight losing patients with cancer compared with weight stable patients and
healthy controls. When FSR was combined with measures of muscle mass it was
demonstrated that only small differences between synthesis and degradation are required to
see the levels of muscle wasting seen in patients with cancer.
In summary, routine cross sectional imaging provides a useful and unique measure of
muscularity that is associated with function in patients with cancer Sequential scans can
provide additional information about changes in body composition even in the absence of
weight loss. There are significant regional variations in both muscle wasting and skeletal
muscle fractional synthetic rate. The combination of sequential estimates of muscle mass
from diagnostic CT scans along with estimates of FSR allow assessment of the contribution
of altered synthesis and degradation to muscle loss. In patients with upper GI cancer it would
appear that increased degradation may be more important that altered synthesis. The relative
change in either process to account for absolute loss of muscle mass is small. Such findings
have implications for the targeted therapy of muscle wasting in cancer patients
Phenotypes and genetic markers of cancer cachexia
No full textCancer cachexia is a chronic wasting syndrome characterised by loss of weight,
composed principally of muscle and fat. Patients with advanced cachexia
demonstrate loss of appetite, early satiety, severe weight loss, weakness, anaemia
and fluid retention. Affected individuals are also likely to report/experience decreased
quality of life, decreased levels of physical performance, increased levels of fatigue,
increased risks of treatment failure (be it chemotherapy, radiotherapy or surgery),
increased risks of treatment side effects, and an increased mortality rate. Cachexia is
therefore an extremely important, yet often underappreciated cause of cancer patient
morbidity and mortality which requires urgent attention. Weight loss is significantly
associated with cancer morbidity and mortality. It has been observed that half of all
cancer patients experience weight loss and one-third lose more than 5% of their
original body weight. Skeletal muscle loss appears to be the most significant event in
cachexia and is associated with a poor outcome. However it is not known why some
patients with the same tumour lose weight and muscle mass whilst others do not.
The main aim of this thesis was to determine if the genetic makeup of individual
patients might contribute to their propensity to lose weight or skeletal muscle.
Previous studies had suggested an association between weight loss and SNPs on
genes concerned with innate immunity and particularly the cell adhesion molecule Pselectin,
however the strength of any gene association study depends on the precision
with which it is possible to characterise the phenotype in question. A second aim of
this thesis was to explore refining the clinical phenotyping of patients to discriminate
those with evidence of muscle fibre atrophy versus those without.
Phenotype
The conventional phenotype for cachexia is weight loss (WL) but it is unknown the
extent to which loss of body mass reflects loss of muscle or fat mass. Recent progress
in cross sectional imaging analysis means that it is now possible to gain a direct
measure of muscle mass from routine diagnostic CT scanning. However, in the
absence of a longitudinal series of scans it is not possible to estimate whether low
muscularity (LM) is longstanding or not. By combining a measure of active weight loss
with low muscularity it was hoped that such a composite measure would reflect actual
muscle loss / fibre atrophy. Compared with non-cachectic cancer patients, patients
with LM or LM+>2%WL, mean muscle fibre diameter was reduced by about 25% (p =
0.02 and p = 0.001 respectively). No significant difference in muscle fibre diameter
was observed if patients had WL alone. Regardless of classification, there was no
difference in fibre number or proportion of fibre type across all myosin heavy chain
isoforms. Mean muscle protein content was reduced and the ratio of RNA/DNA
decreased in patients with either >5%WL or LM+>2%WL.
These findings support the use of composite measures (WL and LM) to try and identify
those patients with evidence of active muscle fibre atrophy. This novel clinical
phenotyping provides an accurate method to enable the conduct of candidate gene
studies in the investigation of the genetics of cancer cachexia where the primary focus
is on muscle wasting rather than overall weight loss.
Genotype
In an ideal world it would be possible to explore the entire genome and look for
associations with the different phenotypes of cachexia. However, to do so would
require considerable resource in terms of the cost of genome wide analysis and the
cost of phenotyping large enough cohorts of patients (3000-10000). To address these
issues I therefore adopted a candidate gene approach. A total of 154 genes
associated with cancer cachexia were identified and explored for associated
polymorphisms. Of these 154 genes, 119 had a combined total of 281 polymorphisms
with functional and/or clinical significance in terms of cachexia associated with them.
Of these, 80 polymorphisms (in 51 genes) were replicated in more than one study
with 24 polymorphisms found to influence two or more hallmarks of cachexia (i.e.
inflammation, loss of fat mass and/or lean mass and reduced survival). Such election
of candidate genes and polymorphisms is a key element of multigene study design.
The systematic review provides a contemporary basis to select genes and/or
polymorphisms for further association studies in cancer cachexia, and to develop their
potential as susceptibility biomarkers of cachexia.
Phenotype – genotype associations
A total of 1276 patients were recruited, phenotyped and genotyped. There were 545
new patients and 731 patients from a previous study. In our new cohort and in keeping
with the previous literature, patients who carried the C allele of the rs6136 SNP in the
SELP gene, were at a reduced risk of developing cachexia defined by WL. This
association applied to all degrees of weight loss (>5%, >10% or >15%), and not just
at the >10% level as described previously in the literature.
When examining newly identified SNPs in a stage 1 analysis for the weight loss
phenotype that included 1276 cancer patients, twelve new candidate SNPs were
significant. Six of these SNPs are associated with muscle metabolism in five genes
(IGF1, CPN1, FOXO1, FOXO3, and ACVR2B), three are associated with adipose
tissue metabolism in two genes (LEPR and TOMM40 (APOE on the reverse strand)),
two with corticosteroid signalling in one gene (IFT172 (GCKR on the reverse strand))
and one with the immune response in one gene (TLR4). Two polymorphisms
(rs1935949 and rs4946935) in the gene encoding for FOXO3 were consistently
associated with WL of increasing severity (>5% and >10%). On the basis that WL is
a continuum in the cachectic process, the observation that both SELP and FOXO3
associate with the higher degrees of WL suggests that these genetic signatures may
be of particular significance. The role of P-selectin in the genesis of cachexia remains
to be determined.
When examining all SNPs in a stage 1 analysis for the LM phenotype, 5 SNPs were
associated significantly with the cachexia phenotype: (i) rs4291 in the angiotensin
converting enzyme (ACE) gene in chromosome 17; this gene has been associated
with muscle function and metabolism; (ii) rs10636 in chromosome 16 in the
metallothionein 2a gene; this gene has been shown to be involved in zinc
dyshomeostasis which may contribute to cancer cachexia; (iii) rs1190584 in
chromosome 14 in the WDR20 gene; this gene encodes a WD repeat-containing
protein that functions to preserve and regulate the activity of the USP12-UAF1
deubiquitinating enzyme complex; (iv) rs3856806 in the peroxisome proliferator-activated
receptor gamma (PPARG) gene in chromosome 3 which has been
demonstrated to be involved in fatty acid and glucose metabolism; and (v) rs3745012
in chromosome 18 in the lipin 2 (LPIN2) gene; this gene represents a candidate gene
for human lipodystrophy, characterised by loss of body fat, fatty liver,
hypertriglyceridemia, and insulin resistance.
When examining all SNPs in a stage 1 analysis for the LM +>2%WL phenotype 4
SNPs were associated significantly with the cachexia phenotype. rs12409877 in the
leptin receptor (LEPR) located on chromosome 3, LEPR binds leptin and is involved
in adipose tissue regulation. rs2268757 located in the activin receptor type-2B
(ACVR2B) gene on chromosome 3, ACVR2B is a high affinity activin type 2 receptor
which mediates signalling by a subset of TGF-β family ligands including myostatin,
activin, GDF11 and others. SNPs in the tumour necrosis factor (TNF) (rs1799964)
and ACE (rs4291) genes were also significantly associated with the phenotype.
Whether genes demonstrating significant associations with the cachexia phenotypes
had altered transcript expression in muscle from cancer patients with or without those
phenotypes was also investigated. Expression of ACVR2B, FOXO1 and 3, LEPR,
PPARG, TLR4, and TOMM40 transcripts was significantly associated with different
levels of skeletal muscle index (SMI) or WL (P<0.05). Specifically, these were all
negatively correlated with muscularity. FOXO1 and 3 and TOMM40 were the only
genes significantly correlated with WL; these were correlated negatively with WL.
Of the SNPs found to be significant across the range of phenotypes the majority are
exons falling within coding sequences of genes or non-coding regions of genes. Some
are introns in the intergenic regions between genes. SNPs may exert differing effects
on genes leading to an aberrant gene product. Polymorphisms in promoter regions
potentially contribute to differential gene expression, presumably affecting the binding
of transcription factors to DNA. Sequence variation in the 5’ untranslated region
(UTR) could disrupt mRNA translation; mutations in the 3’ UTR could affect mRNA
through post-transcriptional mechanisms such as splicing, maturation, stability and
export. Polymorphisms in intronic regions may result in cis- or trans regulation of
genes, unmask cryptic splice sites or promoters leading to alternative transcripts.
Synonymous and non-synonymous SNPs in exons could alter protein function or
activity and may introduce codon bias contributing to the relative abundance of the
proteins, respectively, finally non sense mutations cause a stop altogether in the
translation of mRNA. The genomic distribution of SNPs is not homogenous, SNPs
usually occur in non-coding regions more frequently than in coding regions or, in
general, where natural selection is acting and fixating the allele of the SNP that
constitutes the most favourable genetic adaptation. It has been estimated that 10% of
all SNPs in the genome are functional, thereby having the potential of altering some
biological process. Whether altering function directly or potentially indirectly all could
possibly be used as biomarkers of predisposition to develop cancer cachexia.
The studies presented in this thesis identify new diagnostic criteria that identify
patients with evidence of muscle atrophy. They also confirm previous associations
with patients who carry the C allele of the rs6136 SNP in the SELP gene are at a
reduced risk of developing cachexia defined by WL and beg the question as to the
role of this molecule in cachexia. Whilst achieving these outcomes this thesis also
identifies a set of new SNPs that associate with the phenotype which is shown to
correlate with actual muscle atrophy
Patterning of chorion proteins in the drosophila eggshell
No full textM.S.Includes bibliographical referencesby Kenneth Ki
The implications for ministry of the teachings of Kenneth Cracknell with special reference to former students
No full textTo be effective in ministry in the contemporary religious milieu, today's seminarians, tomorrow's church leaders, must receive more than a mere academic experience; they need practical experience as to how to function effectively within a socially diverse climate of faith. The author documents the long term impact of Kenneth Cracknell's attempts to nurture cross cultural understanding and cooperation within the seminary context. The intent of this exposition is to demonstrate that Kenneth Cracknell has purposefully created a tranformative environment using interfaith dialogue as an effective paradigm for informing today's diverse seminary population. To that end, opinions, reactions and musings of a dozen former students are documented and presented herein as models of appropriate conversation for interfaith dialogue
Cwbr Author Interview: Reluctant Rebels: The Confederates Who Joined The Army After 1861
No full textInterview with Dr. Kenneth W. Noe, Professor of History at Auburn University Interviewed by Nathan Buman Civil War Book Review (CWBR): I\u27m here today with Kenneth Noe, author of Reluctant Rebels: The Confederates Who Joined the Army after 1861. Professor Noe, thank you for joining me. Kenneth Noe (KN): I\u27m happy to be here Nathan
Physical activity level as an outcome measure for use in cancer cachexia trials: a feasibility study
No full textPurpose Cancer cachexia impacts on treatment options, quality of life and survival. New treatments are emerging but need to be assessed using outcomes which patients find meaningful. One approach is the measurement of physical activity levels by small lightweight monitors, but experience is limited in cancer patients. Materials and methods This study formally assessed the acceptability of wearing an ActivPAL™ monitor for 1 week using compliance based on analysis of movement data. The optimal period of monitoring was explored by comparing mean values of daily step count and energy expenditure (EE) for 2 or 4 and 6 days of monitoring. The relationships between step count, stepping EE and non-stepping EE were also explored. Results Sixty patients (mean age 68 years; Eastern Cooperative Oncology Group performance status 0–2) with lung or upper gastrointestinal cancer took part. All but one found that the monitor acceptable and mean [95% CI] compliance was 98% [94–100%]. Median daily step counts and EE scores over 2 or 4 days were significantly higher than those from 6 days (p ? 0.01). Step count was strongly related to stepping and non-stepping EE (r?=
?0.911, p?<?0.01). Conclusions The ActivPAL™ is acceptable to patients with outcomes obtained over 6 days recommended for use in future studies
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