text:
National Cancer Institute®
Last Modified: July 1, 2002
AU - Constantin A; Lauwers-Cances V; Navaux F; Abbal M; van MJ; Mazieres B;
Cambon-Thomsen A; Cantagrel A
Collagenase-1 (MMP-1) and HLA-DRB1 gene polymorphisms in rheumatoid
arthritis: a prospective longitudinal study.
SO - J Rheumatol 2002 Jan;29(1):15-20
AD - Department of Rheumatology and Immunology, CHU Rangueil, France.
OBJECTIVE: Rheumatoid arthritis (RA) is characterized by chronic
synovitis leading to permanent damage of the joints. Collagenase-1
(MMP-1) is a matrix metalloproteinase involved in articular cartilage
degradation. We investigated the association between a biallelic
polymorphism in the MMP-1 gene promoter and the susceptibility to, and
severity of, RA. We also investigated the association between HLA-DRB1
gene polymorphism and severity of RA. METHODS: One hundred and three
patients with early RA were included in this prospective longitudinal
study. A radiographic damage score was used to quantify disease severity
at baseline and after 4 years of followup. MMP-1 polymorphism genotyping
was analyzed using a fluorescent-based polymerase chain reaction (PCR).
HLA-DRB1 genotypes were determined by PCR sequence-specific
oligonucleotide probes. One hundred and thirty-three healthy individuals
were used as controls. RESULTS: MMP-1 allele and genotype frequencies
did not differ between RA patients and controls. The radiographic damage
or its progression over the 4 years of followup did not differ across
MMP-1 genotypes. The radiographic damage score and its progression over
the 4 years of followup differed across HLA-DRB1 genotypes. The HLA-DRB
I shared epitope +/+ genotype was associated with the highest
radiographic damage score and the highest progression, while the shared
epitope -/- genotype was associated with the lowest. CONCLUSION: Our
results do not support the hypothesis of an association between this
particular polymorphism in the MMP-1 gene promoter and susceptibility
to, or severity of, RA. This study confirms the previous reports of an
association between the HLA-DRB1 gene polymorphism and severity of RA.
AU - Donn R; Zeggini E; Shelley E; Ollier W; Thomson W; The British
Paediatric Rheumatology Study Group
Lack of association between juvenile idiopathic arthritis and fas gene
SO - J Rheumatol 2002 Jan;29(1):166-8
AD - ARC Epidemiology Unit, University of Manchester, UK.
OBJECTIVE: Juvenile idiopathic arthritis (JIA) is a complex genetic
disease of autoimmune etiology. Fas is a molecule with a pivotal role in
apoptosis and hence in immune regulation. Elevated transcriptional
levels of Fas in the synovial fluid of patients with JIA suggest that it
might be implicated in disease etiopathogenesis. We investigated whether
a polymorphism in the Fas promoter region (-670) confers susceptibility
to JIA. METHODS: In this association study, 342 UK patients with JIA and
255 healthy individuals were genotyped for the polymorphism using
polymerase chain reaction restriction fragment length polymorphism.
Comparisons of the genotypic frequencies were made using chi-square
analysis. RESULTS: No statistically significant differences were found
when the genotype frequencies of the -670 Fas polymorphism were compared
between the JIA cases and the control panel. Similarly, no differences
were seen between the JIA subgroups, or when the patients were divided
on the basis of rheumatoid factor or antinuclear antibody positivity.
CONCLUSION: The -670 polymorphism of Fas does not appear to be
associated with susceptibility to JIA.
AU - Fabris M; Di PE; D'Elia A; Damante G; Sinigaglia L; Ferraccioli G
Tumor necrosis factor-alpha gene polymorphism in severe and
mild-moderate rheumatoid arthritis.
SO - J Rheumatol 2002 Jan;29(1):29-33
AD - From the Division of Rheumatology, DPMSC, School of Medicine, University
of Udine, Italy.
OBJECTIVE: To examine whether severe rheumatoid arthritis (RA) carries a
-238 or +489 tumor necrosis factor-alpha (TNF-alpha) genotype different
from mild-moderate RA. METHODS: We investigated 163 patients (66 with
severe disease) and 67 healthy blood donor controls. Genotyping was
performed by polymerase chain reaction-restriction fragment length
polymorphism. RESULTS: Patients with severe RA (all active disease
despite disease modifying antirheumatic drug combination therapy)
disclosed the -238 GG genotype in 100% of cases versus 92.8% of the
mild-moderates and 92.5% of controls (OR 11.7, Cl 0.6-216, p = 0.03).
The +489 AA genotype was seen less often in patients than in controls
(OR 4.2. CI 0.97-18.4, p = 0.045), and the contribution to this trend
appeared predominant in the anti-TNF treated subgroup. CONCLUSION: The
-238 AG genotype was absent in severe RA; in contrast, patients with
mild-moderate RA disclosed the same frequency as controls. Thus -238 GG
homozygosity is associated with severe RA. The +489 AA genotype might
instead protect against worse outcome in RA.
AU - Lynch HT; Brand RE; Lynch JF; Fusaro RM; Kern SE
Hereditary factors in pancreatic cancer.
SO - J Hepatobiliary Pancreat Surg 2002;9(1):12-31
AD - Department of Preventive Medicine and Public Health, Creighton
University School of Medicine, 2500 California Plaza, Omaha NE 68178,
The incidence and the mortality rates for pancreatic cancer are the
same, indicating its dismal outlook. Its natural history remains
elusive. Cigarette smoking appears to be the most significant
environmental culprit. Hereditary factors may account for approximately
5% of the total pancreatic cancer burden. However, when its extant
heterogeneity and the reduced penetrance of causal germline mutations
are considered, the hereditary incidence may significantly exceed this
estimate. Even when endoscopic ultrasound (EUS), the gold standard for
pancreatic cancer screening, is utilized, early detection with surgical
cure has rarely been accomplished. Needed to ameliorate this problem is
research into genetic and environmental risk factors and their
interaction. The identification of tumor biomarkers which signal early
pathogenetic events, thereby enabling pancreatic cancer to be diagnosed
at its earliest possible stage before it has spread to regional lymph
nodes or to more distant sites, will improve the outlook. We discuss our
research approaches to this problem. Members of families with the p16
germline mutation will undergo EUS coupled with the collection of
pancreatic juice for the study of a possible gradient for telomerase
activity, K- ras mutations, and cytology. If changes in these putative
biomarkers are observed, endoscopic retrograde cholangiopancreatography
(ERCP) would be the next diagnostic step. We conclude with a discussion
of ethical concerns about this research.
AU - Meiser B; Halliday JL
What is the impact of genetic counselling in women at increased risk of
developing hereditary breast cancer? A meta-analytic review.
SO - Soc Sci Med 2002 May;54(10):1463-70
AD - Department of Psychological Medicine, Royal North Shore Hospital, St
Leonard, NSW, Sydney, Australia. firstname.lastname@example.com
Meta-analytic methods were used to determine the impact of genetic
counselling on women with a family history of breast cancer. Published
studies with prospective designs and randomized controlled trials were
included in the review, and the psychological outcomes assessed were
generalized psychological distress, generalized anxiety, depression, and
breast cancer anxiety. Other outcomes investigated were the accuracy of
perceived risk of developing breast cancer, breast cancer genetics
knowledge and breast cancer screening uptake. A meta-analysis was
performed to estimate effect size, where sufficient data were available.
A total of 12 studies, most of which measured several outcomes, met at
least one of the inclusion criteria. A sufficiently large number of
studies were available to assess the magnitude of effects on three
outcomes: generalized psychological distress, generalized anxiety and
accuracy of perceived risk of developing breast cancer. The quantitative
synthesis showed that genetic counselling leads to statistically
significant decreases in generalized anxiety, with an average weighted
effect sizes of r = - 0.17 (p<0.01). In contrast, the reduction in
psychological distress exhibited a trend towards statistical
significance only, with r = -0.074 (p = 0.052). The impact of genetic
counselling on the accuracy of perceived risk was associated with an
effect size of r = 0.56 (p<0.01). Thus in this meta-analysis, we
demonstrated the efficacy of genetic counselling in meeting two of its
objectives: reducing women's anxiety levels and improving the accuracy
of their perceived risk. This review highlighted that most research so
far focused on generalized distress and anxiety and accuracy of
perceived risk, to the exclusion of other, perhaps equally important,
types of outcomes. Future studies are likely to lead to more
comprehensive assessments if additional emotional, cognitive and
behavioural outcomes are included in the assessment.
AU - Grant SS
Prenatal genetic screening.
SO - Online J Issues Nurs 2000;5(3):2
AD - University of Iowa Hospitals and Clinics, Iowa, USA.
This article presents a discussion of screening principles and
techniques available to screen for common birth defects during
pregnancy. Sixty-five to 70% of women have serum screening and /or
ultrasound during pregnancy to evaluate the health and well-being of the
developing fetus. The most common birth defects identified by screening
include neural tube defects and chromosome abnormalities. Nurses
employed in prenatal care settings need to have accurate information
they can provide to women so they understand the benefits and
limitations of screening. Timely presentation of information and
identification of available resources will help nurses minimize
confusion and provide support for women as they proceed with pregnancy
AU - Williams JK; Schutte DL
Genetic testing and mental health: the model of Huntington disease.
SO - Online J Issues Nurs 2000;5(3):3
AD - The University of Iowa, College of Nursing, Iowa, USA.
Genetic aspects of mental health disorders are being identified through
human genome and family research. Gene discovery makes diagnostic and
presymptomatic testing possible. The discovery of a gene mutation for
Huntington Disease (HD) enables at-risk persons to request
presymptomatic genetic testing. When HD genetic testing is offered
through HD testing centers, a multi-visit protocol is followed in which
education and counseling are provided for persons considering the option
to have HD gene testing. A case study illustrates the clinical and
ethical issues regarding privacy and disclosure as well as the personal
and family consequences of gene mutation knowledge. Analysis of the
impact of genetic knowledge on persons being tested for HD provides a
model for the integration of emerging genetic information into mental
health nursing practice for other mental health disorders.
AU - Greco K; Bayan M
Heart stopper genes: would you recognize a high risk patient?
SO - Online J Issues Nurs 2000;5(3):4
Coronary artery disease (CAD) is one of the leading causes of death in
the United States. Eighty percent of people having heart attacks have
normal cholesterol levels. A quarter of the population have a condition
called low-density lipoprotein (LDL) pattern B that has been associated
with a threefold risk of myocardial infarction. Although early
intervention can often prevent an otherwise fatal event, these patients
often go unrecognized until after a myocardial infarction has occurred
because they may not have the usual risk factors associated with
cardiovascular disease. In patients with LDL pattern B, the standard
lipid panel may be normal and inadequate for diagnosis and treatment of
the condition. This article discusses how to identify a potentially high
risk patient, available laboratory tests, management options, and the
role of nurses in identifying high risk patients. The second author
tells his personal story of surviving multiple cardiac arrests at a
young age before being diagnosed with this condition.
AU - Malchoff CD; Malchoff DM
The genetics of hereditary nonmedullary thyroid carcinoma.
SO - J Clin Endocrinol Metab 2002 Jun;87(6):2455-9
AD - Department of Medicine, University of Connecticut Health Center, 263
Farmington Avenue, Farmington, CT 06030-1850, USA.
AU - Wang H; Chu WS; Hemphill C; Elbein SC
Human resistin gene: molecular scanning and evaluation of association
with insulin sensitivity and type 2 diabetes in Caucasians.
SO - J Clin Endocrinol Metab 2002 Jun;87(6):2520-4
AD - Division of Endocrinology and Metabolism, John L. McClellan Jr. Memorial
Veterans Hospital, 4300 West 7th Street, Little Rock, AR 72205, USA.
Insulin resistance is strongly associated with obesity, but even among
obese subjects insulin sensitivity varies widely. Recently, a new
adipocyte hormone, resistin, was identified, shown to reduce
insulin-mediated glucose uptake, and shown to be increased in obese
mice. We used the chromosome 19 draft sequence to determine the genomic
structure of human resistin and to screen the exons, introns, and
flanking sequences for variation. We screened 44 subjects with type 2
diabetes and 20 nondiabetic family members who were at the extremes of
insulin sensitivity. We identified eight noncoding single nucleotide
polymorphisms (SNPs) and one GAT microsatellite repeat. Three SNPs,
which were in incomplete linkage disequilibrium with each other and had
allelic frequencies exceeding 5%, were selected for further study. No
SNP was associated with type 2 diabetes, but the SNP in the promoter
region was a significant determinant of insulin sensitivity index (P =
0.04) among nondiabetic family members who had undergone iv glucose
tolerance tests. The three common SNPs showed statistical significance
as determinants of insulin sensitivity index (P < 0.01) in interaction
with body mass index. Noncoding SNPs in the resistin gene may influence
insulin sensitivity in interaction with obesity, but this finding will
need to be confirmed in other populations.
AU - Scriver CR
Why mutation analysis does not always predict clinical consequences:
explanations in the era of genomics.
SO - J Pediatr 2002 May;140(5):502-6
AD - Department of Human Genetics, McGill University, Montreal, Quebec,
Canada. firstname.lastname@example.com
AU - Coyne JC; Kruus L; Kagee A; Thompson R; Palmer S; Kruus L
Benign mental health consequences of screening for mutations of
SO - Am J Med Genet 2002 Feb 1;107(4):346-9
AU - Bredart A; Autier P; Riccardo A; Audisio A; Geraghty JG
Psychosocial dimensions of BRCA testing: an overshadowed issue.
SO - Eur J Cancer Care (Engl) 2001 Jun;10(2):96-9
AD - Psycho-Oncology Research Unit, European Institute of Oncology, Milan,
Routine cancer susceptibility testing will soon be feasible in clinical
practice. However, to date, this new technology has entailed many
limitations, including potential adverse psychosocial consequences.
Empirical studies examining these psychosocial aspects are strikingly
scarce, especially in continental European countries. Are we prepared
for managing the psychosocial problems that emerge from widespread
introduction of this practice? Current research do not take into account
cross-cultural variations in attitudes and reactions towards genetic
testing. This paper points to the urgent need for obtaining a more
accurate picture on the psychosocial aspects of breast cancer gene
testing and disclosure in order to design recommendations for
implementation in populations with highly variable cultural and legal
AU - Bazan V; Migliavacca M; Tubiolo C; Macaluso M; Zanna I; Corsale S; Amato
A; Calo V; Dardanoni G; Morello V; La Farina M; Albanese I; Tomasino RM;
Gebbia N; Russo A
Have p53 gene mutations and protein expression a different biological
significance in colorectal cancer?
SO - J Cell Physiol 2002 May;191(2):237-46
AD - Department of Oncology, Regional Reference Center for Biomolecular
Characterization of Neoplasms and Genetics Screening of Hereditary
Tumors of Sicily, University of Palermo, Italy.
p53 alterations are considered the most common genetic events in many
types of neoplasms, including colorectal carcinoma (CRC). These
alterations include mutations of the gene and/or overexpression of the
protein. The aim of our study was to assess whether in 160 patients
undergoing resective surgery for primary operable CRC there was an
association between p53 mutations and protein overexpression and between
these and other biological variables, such as cell DNA content
(DNA-ploidy) and S-phase fraction (SPF), and the traditional
clinicopathological variables. p53 mutations, identified by
PCR-SSCP-sequencing analysis, were found in 68/160 patients (43%) and
positive staining for p53 protein, detected with the monoclonal antibody
DO-7, was present in 48% (77/160) of the cases, with agreement of 57%
(91/160). In particular, a significant association was found between
increased p53 expression and genetic alterations localized in the
conserved regions of the gene or in the L3 DNA-binding domain and the
specific type of mutation. Furthermore, both overexpression of p53 and
mutations in the conserved areas of the gene were found more frequently
in distal than in proximal CRCs, suggesting that they might be
"biologically different diseases." Although p53 mutations in conserved
areas were associated with flow cytometric variables, overexpression of
p53 and mutations in its L3 domain were only related respectively to
DNA-aneuploidy and high SPF. These data may reflect the complex
involvement of p53 in the different pathways regulating cell-cycle
progression. In conclusion, the combination of the mutational status and
immunohistochemistry of p53, and flow cytometric data may provide an
important insight into the biological features of CRCs.
AU - Andersson J; Sjogren H; Meis-Kindblom JM; Stenman G; Aman P; Kindblom LG
The complexity of KIT gene mutations and chromosome rearrangements and
their clinical correlation in gastrointestinal stromal (pacemaker cell)
SO - Am J Pathol 2002 Jan;160(1):15-22
AD - Department of Pathology, Lundberg Laboratory for Cancer Research,
Sahlgrenska University Hospital, Goteborg University, Goteborg, Sweden.
Gastrointestinal stromal (pacemaker cell) tumors (GIST/GIPACTs) are
frequently associated with activating KIT mutations, primarily of exon
11 and rarely of exons 9 and 13, as well as certain chromosome
rearrangements. Reports regarding the frequency and prognostic
significance of KIT mutations are conflicting and few cases have been
completely sequenced. Furthermore, there are few detailed analyses of
chromosome alterations in GIST/GIPACTs. In a detailed analysis of 14
GIST/GIPACTs from 12 patients, we found a wider spectrum of KIT
mutations than previously reported, including 11 different in-frame
mutations involving exons 11, 14, and 15. No mutations were detected in
four malignant tumors. The shorter (GNNK-) KIT isoform was
preferentially expressed. Cytogenetic and spectral karyotype analyses of
10 tumors revealed clonal abnormalities in eight tumors; the most common
were terminal 1p deletions and losses of chromosomes 14 and/or 22.
Neither KIT mutation status nor chromosome aberrations correlated with
tumor phenotype or clinical behavior in our series. Collectively, these
findings indicate that the role of KIT mutations and chromosomal
rearrangements in the pathogenesis of GIST/GIPACTs are more complex than
previously recognized.
AU - Brain K; Gray J; Norman P; Parsons E; Clarke A; Rogers C; Mansel R;
Harper P
Why do women attend familial breast cancer clinics?
SO - J Med Genet 2000 Mar;37(3):197-202
AD - Institute of Medical Genetics, University of Wales College of Medicine,
Heath Park, Cardiff CF4 4XN, UK.
The increasing demand for genetic assessment for familial breast cancer
has necessitated the development of cancer genetics services. However,
little is known about the factors motivating the client population
likely to approach these services. A cross sectional questionnaire
survey of 1000 women with a family history of breast cancer was
conducted to identify self-reported reasons for attending a familial
breast cancer clinic and possible differences in the characteristics of
women who were attending for diverse reasons. Before attendance at
clinic, 833 women completed a baseline questionnaire (83% response
rate). Women who gave personal risk (n=188), awareness of a family
history (n=120), risk to family members (n=84), reassurance (n=69),
genetic testing (n=65), breast screening (n=46), or prevention (n=39) as
their main reason for attending were compared on demographic and medical
variables, and on psychological variables including general anxiety,
cancer worry, perceived risk, and attitudes towards prophylactic surgery
and genetic testing. Important differences in the psychological
characteristics of these groups were found, which were unrelated to
reported family history. In particular, women who primarily wanted
genetic testing felt extremely vulnerable to developing breast cancer,
were more likely to be considering prophylactic surgery, and perceived
fewer limitations of testing. Those who primarily wanted reassurance
were highly anxious about the disease. We recommend that cancer genetics
services take into consideration the informational and psychological
needs and concerns of their client group.
AU - Frontali M; Jacopini AG
Genetic counselling: evolution or involution?
SO - Community Genet 2000 May;3(4):175-8
AD - Instituto di Medicina Sperimentale CNR, Via Fosso del Cavaliere, I-00044
Frascati, Rome (Italy). email@example.com
The need for genetic counselling derives from the peculiarities of
genetic information, as compared to other biomedical tests, with
particular reference to (a) its predictive character; (b) the existing
gap between the ability to diagnose and to treat an inherited disorder,
and (c) the psychological, social and ethical problems that genetic
testing can raise. Counselling is traditionally performed by healthcare
professionals, specifically trained to help individuals to develop ways
of dealing with genetic information and gain a better understanding of
the problems related with it. The growing number of genetic tests (for
rare Mendelian as well as for common disorders), the development of
easier and cheaper molecular techniques, the increasing tendency of
physicians to have recourse to genetic tests, by-passing alternative
diagnostic procedures, are all factors that contribute to the vast
increase in the demand for genetic tests, a demand which is
significantly out of step with the available numbers of trained
counsellors. This paper discusses possible solutions, including the
institution of committees with regulatory powers on genetic testing, the
promotion of studies on models of genetic services, on programmes to
monitor the services currently offered by test providers, and the
expansion of training programmes and of employment opportunities for
genetic counsellors.
AU - Shoskes DA; Albakri Q; Thomas K; Cook D
Cytokine polymorphisms in men with chronic prostatitis/chronic pelvic
pain syndrome: association with diagnosis and treatment response.
SO - J Urol 2002 Jul;168(1):331-5
AD - Cleveland Clinic Florida, Weston and Nova Southeastern University, Fort
Lauderdale, Florida, USA.
PURPOSE: The chronic pelvic pain syndrome is a common disorder of
unknown etiology. Elevated cytokines in prostate fluid and semen are
frequent findings. We studied genetic polymorphisms that can alter
cytokine gene expression in men with the chronic pelvic pain syndrome.
MATERIALS AND METHODS: Genomic DNA was extracted from blood from 36 men
with the chronic pelvic pain syndrome. Reversed sequence specific
oligonucleotide probing was used to genotype the polymorphisms for
cytokine promoter sites, namely tumor necrosis factor (TNF)-alpha 308,
transforming growth factor (TGF)-beta 25, TGF-beta 10, interleukin
(IL)-10 1082 and IL-6 174. Genotype frequencies were compared with 252
controls as well as among groups of patients with the chronic pelvic
pain syndrome according to diagnostic category and treatment response.
RESULTS: There were no differences in men with the chronic pelvic pain
syndrome and control patients in the frequency of TNF-alpha, TGF-beta or
IL-6 alleles, although those with the chronic pelvic pain syndrome were
more likely to express the genotype associated with low IL-10 production
(30.6% versus 12.1%, p = 0.007). When comparing National Institutes of
Health diagnoses, category IIIa patients were more likely to have the
low TNF-alpha genotype (categories II, IIIa and IIIb 33%, 100% and 18%,
respectively, p = 0.04). All 11 of the 28 patients treated with the
anti-inflammatory quercetin in whom treatment failed had the low
TNF-alpha genotype versus 29.4% of those in whom treatment succeeded (p
= 0.0003). Similarly men with quercetin treatment failure were much less
likely to have the low IL-10 genotype than those with treatment success
(9.1% versus 47.1%, p = 0.04). CONCLUSIONS: Patients with the chronic
pelvic pain syndrome are more likely to have a low IL-10 producing
genotype, suggesting autoimmunity as a potential etiology.
Anti-inflammatory phytotherapy failure was associated with low TNF-alpha
and high IL-10 phenotypes, which may help define a subset of patients
with the chronic pelvic pain syndrome without an inflammatory etiology.
AU - Van Asperen CJ; Van Dijk S; Zoeteweij MW; Timmermans DR; De Bock GH;
Meijers-Heijboer EJ; Niermeijer MF; Breuning MH; Kievit J; Otten W
What do women really want to know? Motives for attending familial breast
cancer clinics.
SO - J Med Genet 2002 Jun;39(6):410-4
AU - Geetter JS
Coding for change: the power of the human genome to transform the
American Health Insurance System.
SO - Am J Law Med 2002;28(1):1-76
AD - McDermott, Will & Emery, Boston, Massachusetts, USA.
AU - Ye J; Liu X; Huang X
[Screening for 6-pyruvoyl-tetrahydrobiopterin synthase (PTPS)
deficiency: clinical analysis of 9 patients with PTPS deficiency]
SO - Zhonghua Yi Xue Za Zhi 2000 Jul;80(7):513-5
AD - Shanghai Institute for Pediatric Research, Shanghai 200092, China.
OBJECTIVE: To show the incidence of 6-Pyruvoyl-tetrahydrobiopterin
synthase (PTPS) deficiency among hyperphenylalaninemia and conclude the
clinical outcome of patients with PTPS deficiency. METHODS: The urinary
neopterin (N) and biopterin (B) were determined by HPLC in 69 PKU cases.
BH(4) loading test and mutation analysis of PTPS were performed in
patients who had abnormal urinary pterin patterns. Three patients with
PTPS deficiency were placed on treatment with combined synthetic BH(4)
and neurotransmitter precursors such as Dopa and 5-hydroxytryptophan.
RESULTS: 9 out of 69 patients, whose urinary N/B exceed 38 [normal: 1.17
(1.4)] and B% were less than 5% [normal: 55.9 (18.6)], were diagnosed as
having PTPS deficiency. Four kinds of PTPS gene mutations (P87S, N52S,
D96N and G144R) were detected from 4 out of 9 cases with PTPS
deficiency. The last mutation was a new mutation. The three typical
PTPS-deficient patients had satisfactory physical development, their
intelligence quotient (IQ) were 70 approximately 80 after treatment and
one partial PTPSD had normal growth and mental development. CONCLUSION:
The screening for BH(4) deficiency should be carried out among all
patients with hyperphenylalaninemia in order to avoid misdiagnosis.
AU - Murphy AE
Cancer genetics.
SO - Eur J Cancer Care (Engl) 2001 Mar;10(1):66-8
AD - Geneva University Hospital, Switzerland.
AU - Mahon SM
Factors affecting genetic testing and decisions about prophylactic
SO - Clin J Oncol Nurs 2001 May-Jun;5(3):117-20
AD - St. Louis University, Division of Hematology/Oncology, St. Louis, MO,
Both of the articles reviewed here as well as the references, suggest
that very little is actually known about the impact of many aspects of
genetic testing. How decision are made about genetic testing in people
who do not have cancer, how the results of testing are used used to
guide care, and ultimately how people adjust to prophylactic surgery,
which is the most effective form of prevention currently available to
those who do have a mutation are not completely clear. This has many
implications for practice in general. Oncology nurses who build
relationships with those diagnosed with cancer and their families may be
one of the best groups of professionals to provide the education and
counseling individuals and families need prior to making any decision
about genetic testing. Just as many responses to cancer exist, so do
many responses to finding out the results of mutation status. Oncology
nurses are challenged to help facilitate adjustment to learning that one
carries a mutation that significantly increases risk of developing
cancer. More nursing research needs to be conducted on how to facilitate
this adjustment. Dealing with the unknown can be a frightening
experience. Little is known about the long-term effectiveness of
prophylactic mastectomy and oophorectomy in unaffected mutation-positive
individuals. Most of what is known is based on retrospective review.
Nurses are challenged to interpret this information, along with its
inherent strengths and weaknesses, to individuals so they can make the
best possible decisions. The psychosocial needs of those who undergo
prophylactic surgery are not clearly understood. Surgery can have many
psychological outcomes, and how individuals adjust to these changes is
not clear. More nursing research is needed not only to understand these
needs but also to design interventions to facilitate and improve
adjustment to not only the information that one is mutation positive but
also to prophylactic surgery. People who do not have cancer but have a
high risk for cancer because of their genetic background need
comprehensive and consistent care by knowledgeable healthcare providers.
Although these individuals have not been diagnosed with cancer, they
have complex psychosocial needs related to their family history and the
decisions being made about prevention strategies. Oncology nurses can
help fill this gap in care and provide the necessary support these
individuals need.
AU - Zawacki KL; Phillips M
Cancer genetics and women's health.
SO - J Obstet Gynecol Neonatal Nurs 2002 Mar-Apr;31(2):208-16
AD - School of Nursing, The Johns Hopkins University School of Nursing,
Baltimore, MD 21205, USA. email@example.com
It is now known that all cancer is genetic in origin. Although most
cancer occurs by chance, approximately 5% of individuals inherit
specific genetic mutations that predispose them to cancer. The genetic
characteristics of some cancers are known. Such information can be
useful to health care providers in the clinical setting for treatment,
early detection, and prevention. This article reviews basic
carcinogenesis as well as genetic syndromes that predispose women to
breast, ovarian, colorectal, and endometrial cancer. Knowledge of
hereditary cancer syndromes and familiarity with them will assist the
advanced practice nurse in the management of patients who are at risk.
Cancer continues to contribute substantially to the mortality of women
in all age groups. Knowledge of these syndromes provides an excellent
opportunity to decrease mortality by early detection and prevention.
AU - Thiede C; Steudel C; Mohr B; Schaich M; Schakel U; Platzbecker U; Wermke
M; Bornhauser M; Ritter M; Neubauer A; Ehninger G; Illmer T
Analysis of FLT3-activating mutations in 979 patients with acute
myelogenous leukemia: association with FAB subtypes and identification
of subgroups with poor prognosis.
SO - Blood 2002 Jun 15;99(12):4326-35
AD - Medizinische Klinik und Poliklinik I, Universitatsklinikum Carl Gustav
Carus der Technischen Universitat, Dresden, Germany.
Constitutive activation of the FLT3 receptor tyrosine kinase, either by
internal tandem duplication (ITD) of the juxtamembrane region or by
point mutations in the second tyrosine kinase domain (TKD), has been
described in patients with acute myelogenous leukemia (AML). We analyzed
the prevalence and the potential prognostic impact of FLT3 mutations in
979 AML patients. Results were correlated with cytogenetic data and the
clinical response. FLT3-ITD mutations were found in 20.4% and FLT3-TKD
mutations in 7.7% of the patients. Each mutation was associated with
similar clinical characteristics and was more prevalent in patients with
normal karyotype. Significantly more FLT3 aberrations were found in
patients with FAB M5, and fewer were found in patients with FAB M2 and
M6. Although less frequent in patients with cytogenetic aberrations,
FLT3-ITDs were found in 13 of 42 patients with t(15;17) and in 9 of 10
patients with t(6;9). The prevalence of the ITD allele on the DNA level
was heterogeneous, ranging from faint mutant bands in some patients to
predominant mutant bands in others. Based on quantitative analysis, the
mutant-wild-type (wt) ratio ranged from 0.03 to 32.56 (median, 0.78).
Patients with a high mutant/wt ratio (ie, greater than 0.78) had
significantly shorter overall and disease-free survival, whereas
survival in patients with ratios below 0.78 did not differ from those
without FLT3 aberrations. Multivariate analysis confirmed a high
mutant/wt ratio to be a strong independent prognostic factor. Taken
together, these data confirm that FLT mutations represent a common
alteration in adult AML. Constitutive activation may be associated with
monocytoid differentiation. A high mutant/wt ratio in ITD-positive
patients appears to have a major impact on the prognostic relevance.
AU - Andresen PA; Gedde-Dahl T Jr; Fausa O; Eide TJ; Heiberg A
[Genetic analysis in familial adenomatous polyposis]
SO - Tidsskr Nor Laegeforen 2001 Jan 10;121(1):64-8
AD - Patologisk-anatomisk avdeling 9038 Regionsykehuset i Tromso.
BACKGROUND: Familial adenomatous polyposis (FAP) is an autosomal
dominantly inherited disorder caused by germline mutations in the APC
gene. FAP is characterised by a variable, but normally large number of
colorectal adenomas and variations in extracolonic manifestations. These
variations are associated with specific mutations of the APC gene.
MATERIAL AND METHODS: Representatives from 70 Norwegian families are
under molecular investigation. Analyses have so far been concentrated on
the part of the APC gene associated with classic FAP. RESULTS: Germline
mutations causing FAP have been identified in 36 of the 70 families
examined. All mutations identified are confined to the first half of the
gene and correlate to classic FAP. INTERPRETATION: Because of the
mutation heterogeneity in FAP, the size of the APC gene and variations
in phenotype, it is a laborious task to identify the causative
mutations. Better approaches to the analysis of the whole APC have now
been established and will result in a higher degree of mutation
detection independent of phenotype. Family history and
phenotype-genotype correlations are still important guidelines for
efficient molecular genetic analysis of the APC gene. Genetic
surveillance, personal and socio-economic benefits from presymptomatic
and predictive testing of members of FAP families are discussed.
AU - Friedenson B
A current perspective on genetic testing for breast and ovarian cancer:
the oral contraceptive decision.
SO - MedGenMed 2001 Nov 2;3(6):2
AD - Department of Biochemistry and Molecular Biology at the University of
Illinois at Chicago, Chicago, Illinois, USA. firstname.lastname@example.com.
A clinician faces a problem in how best to counsel the woman with a
family history of breast or ovarian cancer about her options for
pregnancy prevention. The physician must guide her as she makes new and
complex decisions. Recent data strongly support an amplified effect of
the estrogens in oral contraceptives for the woman with a genetic risk
for breast cancer. Nonetheless, a woman's immediate need to prevent
pregnancy may be much more important to her than worrying about the
long-term risk of breast cancer. Another factor is that oral
contraceptives prevent ovarian cancer, so the physician may wish to
prescribe them to protect her from ovarian cancer. In some genetic
backgrounds, however, oral contraceptives not only do not prevent
ovarian cancer, but they may raise the risk of breast cancer so
significantly that they should not be taken. With other genetic
backgrounds, oral contraceptives will protect the woman from ovarian
cancer without much effect on her breast cancer risk. When does each of
these cancer risks or benefits become significant? The clinician can
provide an important benefit to a woman who must prevent pregnancy yet
worries about her cancer risk. The physician can help her evaluate the
evidence, with its gaps and uncertainties, in the context of her own
preferences. To assist in this evaluation, this decision aid provides
base-line estimates of the cancer risk that accompanies each of a
woman's options. In some cases, genetic testing is likely to provide
valuable information as she makes choices about contraception and the
risks vs. benefits of different alternatives available to her.
AU - Revilla M; Obach V; Cervera A; Davalos A; Castillo J; Chamorro A
A -174G/C polymorphism of the interleukin-6 gene in patients with
lacunar infarction.
SO - Neurosci Lett 2002 May 10;324(1):29-32
AD - Service of Neurology, Hospital Clinic Universitari, Villarroel 170,
08036 Barcelona, Spain.
Interleukin-6 (IL-6) is a pleiotropic cytokine that plays a central role
in the pathogenesis of stroke. A base pair substitution -174G/C in the
promoter region of the IL-6 gene regulates IL-6 gene expression. We
compared the prevalence of this polymorphism in patients with lacunar
stroke and in an age- and sex-matched cohort of asymptomatic controls.
Eighty-two patients with lacunar stroke and 82 asymptomatic controls
were prospectively assessed and genotyped for the -174G/C polymorphism
in the promoter region of the IL-6 gene. Demographics and vascular risk
factors were recorded in both groups. A brain computed tomography
scan/magnetic resonance imaging confirmed the clinical diagnosis of
lacunar stroke in all patients. The prevalence of CC genotype (18.3 vs.
7.3%, P=0.03), and the frequency of C allele (42.7 vs. 31.1%, P=0.03)
were statistically significantly higher in patients with lacunar stroke
than in asymptomatic controls. Expectedly, patients with lacunar stroke
had a higher prevalence of vascular risk factors than asymptomatic
controls. A logistic regression model showed that independent variables
associated with lacunar stroke included history of hypertension (odds
ratio (OR), 7.02; 95% confidence interval (95% CI), 3.11-15.81),
diabetes (OR, 5.37; 95% CI, 1.52-8.89), hyperlipidemia (OR, 3.43; 95%
CI, 1.04-11.25), smoking (OR, 5.84; 95% CI, 2.15-15.84), and CC genotype
of the -174G/C IL-6 gene polymorphism (OR, 4.28; 95% CI, 1.22-15.00).
These findings suggest that lacunar stroke might result from genetic
susceptibility to inflammation-mediated damage in concert with
atherosclerotic risk factors.
AU - Pendleton N; Payton A; van den Boogerd EH; Holland F; Diggle P; Rabbitt
PM; Horan MA; Worthington J; Ollier WE
Apolipoprotein E genotype does not predict decline in intelligence in
healthy older adults.
SO - Neurosci Lett 2002 May 10;324(1):74-6
AD - Clinical Gerontology Group, Clinical Division I, University of
Manchester, Hope Hospital, Stott Lane, Salford, M6 8HD, UK.
There is evidence of a genetic influence on the decline in cognitive
performance of older adults, although the mechanisms responsible are
unknown. A group of 767 subjects of the Manchester University Age and
Cognitive Performance longitudinal study volunteer group, followed up
from 1985 to the present, were genotyped for apolipoprotein E (APOE).
The data from this were related to cross-sectional and longitudinal
trends in the Heim intelligence test score (AH4-1) using previously
reported random-effects models (Neuropsychologia 39 (2001) 532). There
were no significant differences in mean scores for presence compared
with absence of the APOE4 or APOE2 genotypes (P=0.48 and P=0.51,
respectively). This research does not demonstrate a link between
intelligence and APOE genotype in older adults.
AU - Henderson JN; Crook R; Crook J; Hardy J; Onstead L; Carson-Henderson L;
Mayer P; Parker B; Petersen R; Williams B
Apolipoprotein E4 and tau allele frequencies among Choctaw Indians.
SO - Neurosci Lett 2002 May 10;324(1):77-9
AD - Department of Health Promotion Sciences, University of Oklahoma,
Oklahoma City 73190, USA.
Apolipoprotein genotyping and tau haplotyping were carried out on a
series of cases with dementia and controls from the Choctaw Nation of
Oklahoma. Both the Apolipoprotein E4 allele frequency and the tau H2
haplotype frequency were low in the Choctaw compared with Caucasians and
there was the possibility that the association between dementia and the
E4 allele was weaker than in Caucasians.
AU - Green EK; Thaker U; McDonagh AM; Iwatsubo T; Lambert JC; Chartier-Harlin
MC; Harris JM; Pickering-Brown SM; Lendon CL; Mann DM
A polymorphism within intron 11 of the tau gene is not increased in
frequency in patients with sporadic Alzheimer's disease, nor does it
influence the extent of tau pathology in the brain.
SO - Neurosci Lett 2002 May 17;324(2):113-6
AD - Department of Psychiatry, University of Birmingham, Birmingham B15 2QZ,
There are numerous polymorphisms within the tau gene but these are in
complete linkage disequilibrium and exist as two common extended
haplotypes H1 and H2. We have investigated the frequency of these
haplotypes in 83 cases of sporadic Alzheimer's disease (AD) using the
+34 polymorphism in intron 11 of the tau gene as a marker of H1 and H2
haplotypes. The total amount of hyperphosphorylated tau protein (tau
load), present as neurofibrillary tangles, neuropil threads or plaque
neurites, was quantified in the frontal cortex of these patients and
related to tau haplotype. We found no increase in H1H1 haplotype in this
autopsy population of cases with AD compared to published control data.
Stratification of cases for apolipoprotein E (APO E) genotype showed a
slight, but not statistically significant, overrepresentation of epsilon
4 allele amongst bearers of H2 haplotype. There were no overall
differences in tau load between haplotype groups though cases within
each haplotype group bearing APO E epsilon 4 allele had a significantly
higher tau load than those without epsilon 4 allele. Neither age at
onset or duration of illness differed according to tau haplotype. We
conclude that the frequency of tau gene H1 haplotype is not elevated in
AD and possession of this has no impact upon the amount of tau pathology
in AD.
AU - Cooper EB
Testing for genetic traits: the need for a new legal doctrine of
informed consent.
SO - MD Law Rev 1999;58(2):346-422
AU - Schutzer PJ
Genetics and ethics.
SO - Pharos Alpha Omega Alpha Honor Med Soc 1995 Winter;58(1):26-31
AU - Jakobovits I
Some modern responsa on medico-moral


text:
It's Grape Season- Don't be a Prune! Be Juicy and Fun in June!
If you are in LA this summer you are a lucky mothersucker because not ONLY do we live in a fly city, but there's always really cool events happening around town, most of which are FREE; and ALL of which are rockin' and poppin' with creativity, music, art or all of the above combined! Here's a list of some of the events coming up in June alone! Let us feel alive this summer and engage in in art, music, dance and love. No Regrets!
May 27-Sept 3: Ends of the Earth: Land Art to 1974 @ MOCA Geffen
June 2-September 2: Made in LA Art Show @ Hammer Museum
Jun 11-13: Dodgers vs. Angels Rivalry @ Dodger Stadium
June 11: Annie Hall @ Downtown Independent Theater 9pm
June 11- 14: Celine and Julie go Boating @ Cinefamily 8pm
June 12: Jiro Dreams of Sushi @ New Beverly Theater 7:30pm
June 14-July 29: War Horse @ Ahmanson Theater
June 15: Buffy Vampire Slayer/The Craft @ Downtown Independent 7pm
June 16: LA Muse Art Walk and After Party 6pm-midnight @ LACMA
June 17: Charlie Chaplin's "The Kid" @ Cinefamily 4pm
June 17,18: Woody Allen double feature @ New Beverly 7:30pm
June 22-June27: Beyond the Black Rainbow @ Cinefamily
June 22: Dirty Dancing Dance-Along @ Grand Performances 8pm
June 23: Forbidden Zone @ Aero Theater
June 23: Chinatown (dir. Polanski) @ Hollywood Forever
June 25: Accordion night at The Ford Amphitheater 7pm
June 27: 3 Women (dir. Robert Altman) @ Aero Theater 7:30pm
June 28: Hammer Bash-Made in LA Party @ Hammer Museum 7pm
June 28-Sept 2: Shakespeare in the Park: www.iscla.org
June 29: Pink Floyd The Wall @ Aero Theater 7:30pm

subset: commoncrawl


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Ends 07/14/13. Go behind the scenes of the HBO series 'The Newsroom.' Watch 'The Newsroom 10' on HBO on xfinityTV.com watch
Get to know volatile ACN news anchor Will McAvoy of 'The Newsroom' with Jeff Daniels, Aaron Sorkin, and others. watch
An introduction to the characters and storylines of the HBO series 'The Newsroom' with creator Aaron Sorkin, star Jeff Daniels, and others. watch
The Newsroom's second season will premiere on ... read more
The Newsroom actress Alison Pill and Jay Baruchel have ended their engagement, US Weekly reports.
Pill, 27, and Baruchel, 30, met on the set of the film Goon and got engaged in December 2010. Although they were planning to wed in September 2012, the nuptials were postponed.
Aaron Sorkin is well aware that critics had a lot to say about The Newsroom's first season. Whether he plans to do anything differently with regard to the many complaints is a different story.
"As far as criticism goes, there was a lot, so it would be hard to address this and not that," Sorkin, the show's creator and executive producer, told TVGuide.com at Sunday's PaleyFest panel. "There are plenty of TV critics I respect, and I read them and I think about what they're saying. But when it comes time to write, you really got to go in and do your thing and not have too many voices in your head."
Terry Crews has joined the cast of the untitled Fox comedy from Parks and Recreation's Mike Schur and Dan Goor.
The project stars Saturday Night Live alum Andy Samberg as one of a diverse group of detectives at a New York police precinct. Crews will play... read more
Oscar winner Marcia Gay Harden is heading to The Newsroom to replace Rosemarie DeWitt, Entertainment Weekly reports.
DeWitt left the HBO drama last week after shooting a handful of episodes. HBO said DeWitt's early departure was because of.... read more
more The Newsroom products


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Category: The Man Issue
Manly Cocktails At St. Charles Exchange
Chris George is a master when it comes to mixing up drinks of all manner, but the St. Charles Exchange bartender is exceptional at recommending manly drinks.
Marrying Fitness Into Your Relationship
Do you want your family to be healthy? Do you want to feel good? Do you want a sexy spouse? Two weeks ago, I got to marry the love of my life. We dated for six years through high school and college before taking a 10-year break that ended when we realized we had wasted [...]
Santa Shares The Gift Of Humility
Sporting a Hawaiian shirt and red shorts with his signature bushy white beard, Santa Claus stands out in any crowd, even in the middle of summer.
Five Books Every Man Should Read
There's nothing like a good read to take your mind off a long, stressful workday.
In His Own Words: Sam Swope On Why Real Men Give Back
There's nothing more appealing than a man who shares his heart with the world, which is why Sam Swope is one of our favorite philanthropic fellas.
Not Your Mediocre Man Cave
While most "man caves" consist of poker tables, big-screen TVs and refrigerators full of beer, Danny Ruckriegel's cave, located in the basement of his home, holds much more significance than that.
Tattoos & Tiramisu
You don't have to be a Food Network fan to see that cooking is an art enjoyed by the manliest of men.


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People visit the beaches in New Jersey all year round but most people visit during spring and the summertime for spring break, romantic weekend getaways, holidays, family vacations, business, extended stays, short breaks from work and more. Many people choose a beach in New Jersey for the perfect wedding or honeymoon destination.
New Jersey has over 127 miles of shoreline. You can find shoreline rentals, cottages for rent, beach vacation rentals, oceanfront resorts, villas, historic inns, suites, apartments, vacation studios and more accommodations. Most beaches have lifeguards and are handicapped accessible. Some beaches have a beach fee, tennis courts, boat ramps, bathhouses, picnic areas, amusement arcades and a boardwalk.
Atlantic City is famous for its boardwalk, white sandy beaches and gambling casinos. There are convention centers here too. It is a year round resort. Come by yourself and gamble in a casino. Bring a companion for a romantic getaway. Or bring your entire family for a great vacation in the sun. Visit Steel Pier Amusement Park for a day of fun. Go shopping . There is a little something for every member of the family to do here.
The Jersey shore has 2 beach state parks. Sandy Hook State Park is in northern New Jersey and Island Beach State Park which is located in the Southern part of the region near Seaside Park. Camp. Take a cruise. See dolphins or whales. Bird watch. Climb a lighthouse. Learn about history. Explore the marsh, beach and meadows. Golf. Visit art galleries, historic sites and museums. Hike. Bike. The area offers fun and excitement as well as a chance to relax and enjoy a sunset or sunrise.
On the Southern Shore, Cape May was the first US seaside resort. Take the Cape May Lewes Ferry to the Delaware shore. Cape May has many Victorian houses and other historic places to visit or stay. In the area, stroll through beautiful flower gardens. See glass blowing demonstrations and exhibitions of glasswork. Sail a boat. Watch wildlife in a zoo. See dolphins play. Watch for whales. Go deep sea Fishing Spots. In Wildwood, visit Morey's Piers for games, rides and water park fun. Take guided kayak tours, walks and back bay boat rides at the Wetlands Institute in Stone Harbor.
Stroll on the beach with your lover hand in hand. Enjoy the day. Climb a lighthouse. Watch the sea gulls. Play in the sand. Build sand castles. feel the sand between your toes. Jump the waves. Surf. Kite board. Sail a sailboat. Go scuba diving, parasailing, bodysurfing, boating ... Relax and doze in the sun as you feel the warmth of the sun and hear the waves lap the shore. Don't forget the sunscreen. Enjoy a cold drink. Cool off with a dip in the Ocean. Walk on the boardwalk, pier or the shoreline. Play the arcade. See fisherman catch fish or just watch the fish swim under and around a pier. Charter a boat to go deep sea fishing. Take a cruise. Watch dolphins in the surf. Eat dinner at a seafood restaurant and relish fresh shrimp, grouper or your favorite fish. Watch the sunset. Its beautiful. The end of a perfect vacation day at the beach.
New Jersey Beaches


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This iconic grunge band was a huge part of the reason Seattle stood as the epicenter of the music world in the early 90s, and with Soundgarden tickets you can witness these GRAMMY-winning alternative rockets play their latest hits and show why they'll go down as one of America's greatest bands.
Featured Events
Music fans are uncovering great bargains on Soundgarden tickets every day on VividSeats.com! The grunge rock demigods have reunited and are ready to fill a concert venue near you with their surreal rock sound. Outfitted with eerily complex guitar riffs and Chris Cornell's vast vocal dexterity, Soundgarden recorded some of the best rock albums of the nineties. Soundgarden concert tickets can be tracked down using Vivid Seats whenever the Seattle-founded quartet goes on tour. We make an effort to keep our customers informed about when Soundgarden tour dates are announced and other vital Soundgarden information.
In support of their latest studio album, King Animal, the ageless rockers comprising Soundgarden have lined up a wealth of winter shows for their month-long 2013 North American Tour. Following a two-night stint in Chicago, Chris Cornell and company will perform 10 more dates throughout February. Slated to host shows are venues in Milwaukee, Minneapolis, Portland, Seattle, Vancouver, Oakland, and Los Angeles, and fans can purchase 2013 Soundgarden tickets now from the Vivid Seats marketplace.
The band also has booked three consecutive performances in May. On the 17th, they play at the Columbus Crew Stadium in Ohio, followed by the Susquehanna Bank Center in Camden, N.J., the following night along with Alice in Chains and Cheap Trick, before heading back to Columbus to perform at the Rock on the Range on the 19th. Check back often as more Soundgarden tour dates may be added later in the year.
Regrouped and refocused, Soundgarden is currently at work recording their first studio album in 15 years. Chris Cornell, Ben Shepherd, Matt Cameron, and Kim Thayill have bunkered down in the studio with producer Adam Kasper (Pearl Jam, Foo Fighters) and are reportedly close to finishing the record. The album is supposed to be very different from any other record the band has put out in the past. 2011-2012 Soundgarden tickets have just been made available to the public for the band's fall and winter tour dates. Only a handful of shows have been announced thus far, but more are expected to be released shortly. The infamous alternative rockers will also be heading down under for a quick tour of Australia in late January. Soundgarden is back and the world of rock 'n' roll is all the better.
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TechNotes # 4
SBIC TechNotes
July 1998 - Number 4
Sections 107.503 and 107.650 of the SBA regulations require SBICs to value their portfolios periodically and to report the valuations to SBA. In 1995, SBA issued a memorandum to licensees that provided additional information concerning the prescribed form and content of the required valuation reports (memorandum #95-9, June 27, 1995). Because of the passage of time and the number of new licensees that have entered the SBIC program since then, we are presenting the information again in this edition of TechNotes.
Regulatory Provisions
The regulatory requirements concerning frequency of valuations are found in § 107.503(d), which reads as follows:
(d) Frequency of valuations.
(1) If you have outstanding Leverage or Earmarked Assets, you must value your Loans and Investments at the end of the second quarter of your fiscal year, and at the end of your fiscal year.
(2) Otherwise, you must value your Loans and Investments only at your fiscal year end.
(3) On a case-by-case basis, SBA may require you to perform valuations more frequently.
(4) You must report material adverse changes in valuations at least quarterly, within thirty days following the close of the quarter.
The regulatory requirements concerning the reporting of valuations to SBA are found in § 107.650, which reads as follows:
You must determine the value of your Loans and Investments in accordance with § 107.503. You must report such valuations to SBA within 90 days of the end of the fiscal year in the case of annual valuations, and within 30 days following the close of other reporting periods. You must report material adverse changes in valuations at least quarterly, within 30 days following the close of the quarter.
Reports to SBA
Annual Valuation Reports - The annual valuation requirement applies to all SBICs. You satisfy this requirement by filing SBA Form 468, which includes valuation information in the Schedule of Loans and Investments (page 12P or 12C of the form). If you have portfolio securities that have changed in value by more than plus or minus 10 percent since your last valuation report, you must identify them in a supplementary schedule. This schedule, which may be included with the footnotes to the Form 468 financial statements, should show the name of the portfolio company, cost of the investment, current Asset Value, previous Asset Value, and the reasons for the change in the valuation. "Asset Value" is a defined term in SBA's Valuation Guidelines for SBICs that means fair value as determined by a licensee's board of directors or general partners.
Semi-annual Valuation Reports - The semi-annual valuation requirement applies to leveraged SBICs (and to SBICs that have redeemed all their Participating Securities leverage, but still have Earmarked Assets in their portfolios). Although not specifically required by regulation, SBA is asking SBICs with outstanding leverage commitments to comply as well. You satisfy this requirement by submitting a schedule to SBA listing all your portfolio securities that have changed in value by more than plus or minus 10 percent since your last fiscal year end. The schedule should show the name of the portfolio company, cost of the investment, current Asset Value, previous Asset Value, and the reasons for the change in the
If you do not have any such securities, you must send SBA a written certification containing the following language: "The Asset Value of each portfolio security has not changed by more than plus or minus 10 percent from the Asset Value at the end of the previous fiscal year, excluding changes due to additional financings or repayment of principal by the portfolio concern." An officer or general partner of the SBIC must sign the certification. In addition to the required schedule or certification, you must file a schedule summarizing your portfolio as of the end of your second fiscal quarter, using the following format (the line items correspond to those in the Loans and Investments section of the Statement of Financial Position, page 2P or 2C of SBA Form 468):
Quarterly Valuation Reports - You must file a quarterly valuation report only when there is a material adverse change in the value of one or more of your Loans and Investments since your last required report. For this purpose, "material" means a decrease of more than 20 percent in the Asset Value of any individual portfolio security. Your report should list each such security in a schedule showing the name of the portfolio company, cost of the investment, current Asset Value, previousAsset Value, and the reasons for the change in the valuation.
Information Retained in Licensee's Files
In addition to the valuation reports you send to SBA, you must keep more detailed information about your portfolio valuations in your files. The Valuation Guidelines for SBICs require that you prepare and retain valuation reports for each portfolio security. These reports must document the cost, current fair value and previous fair value, plus the methodology (i.e., the basis for the valuation as set forth in your valuation policy) and the supporting data used to determine the value of each portfolio security as of each valuation date. You may use any format for these reports, as long as they contain the required information. Although you need not file these reports with SBA on a regular basis, you must make them available
for review by SBA's examiners and must provide copies to other SBA staff upon request.
If you have any questions about valuation requirements, please consult your SBA account executive or area chief.
Content comments or questions to: firstname.lastname@example.com


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On Boston and Empathy
April 16, 2013 Empathy. The "chameleon" of human emotions. The ability to "feel" what others feel. With empathy, just like any emotion, some are more capable than others. ANGER: some of us fly into blind rages while others seethe. HAPPINESS: one 8-year old who screams as she unwraps the gift she's asked for all year, another silentlyCover Lay Down – 3/2/13
March 20, 2013 As most of you know, I released a 5 song covers album entitled Antipodes a few weeks back. Two of the songs from the album landed on a great blog called Cover Lay Down. Below is an excerpt from the blog but do yourself a favor and go visit the entire siteWhat Does an Indie Get Paid? #4 – Spotify
February 14, 2013 I'm doing a multiple-part series on how Independent Artists get paid. Part one (iTunes). Part Two (International / Other Downloads). Part Three (Streaming: All But Spotify). PART FOUR – SPOTIFY I get asked this question a lot: "How much do you make from Spotify?" It's a fair question: Spotify launched, and suddenly we had(Time Out)
February 12, 2013 Hey all. I am still writing entries for this "What Does an Indie Get Paid" series, but the fact is, the articles are getting a little bit more complicated as they go, so I want to make sure I'm getting my numbers right. In the meantime, I got this comment on article


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Hotel Pio
Italian style mini-hotel located in the historical and artistic area of the Saint-Petersburg...
Mini-hotel 'Pio', located in the historic center of St. Petersburg, a five minute walk from Nevsky Prospect, which is the best place to start exploring the city.Comfortable mini-hotel 'Pio' offers you 13 standard rooms and two-bedroom apartment on Mokhovaya Street. Rooms are decorated in Italian style, perfect for tourists and families with children, as well as for business people. Each room is equipped with shower, toilet, hairdryer, TV and telephone. At the disposal of our guests a fully equipped kitchen, home decor reminiscent, 6 options to choose from breakfast guests and non-stop access to the Internet.A list of additional services includes use of laundry facilities, sauna, taxi services, translation services, information about the cultural life of the city and excursions, booking venues (theaters, museums, etc.), visa support, registration of foreign citizens. |
Availability & Rates
To view availability and prices please select dates and click 'Update Dates'Hotel Facilities
- 24 hour reception
- 24 hour security
- Adaptors
- Airport transfers
- Book exchange
- Breakfast Included
- Cots available
- Currency exchange
- Free City Maps
- Free Parking
- Free Wifi
- Hair Dryers
- Laundry Facilities
- Luggage Storage
- Parking
- Postal Service
- Safety Deposit Box
- Tea/Coffee Making Facilities
- Tours Travel Desk
Cancellation Policy
This property has a 1 day cancellation policy. Failure to cancel within this time will result in a cancellation charge equal to the first night of your stay.DirectionsShow MapHide Map
Mini-hotel at Mokhovaya 39 (intercome - 10) is situated near the Circus 'Chinzelli' in the center of the city.The nearest subway station - Gostiny Dvor(10 min), railway station - Moskovsky Vokzal (15 min) Mini-hotel at Griboyedova 35 (intercom - 5),the nearest subway station - Nevsky Prospect (3min) and railway station - Moskovsky Vokzal (20 min)


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ivivva blog
make every second count.
It's crunch time and we know you girls are working your tails off right now as you train for your final competitions and exams.
read more -
new showrooms hit the USA
You asked and we're answering: ivivva is opening 3 new showrooms in the USA this May – and 3 more in the summer!
read more -
yoga mats are here!
ivivva's yoga mats have arrived!
read more


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Changed her eyecolor from purple to brown and gave her some new lips...she's feeling a little happier today. Hope you like! xoxo
Add a Comment
Hi Jared!!! *waves frantically* I'm thrilled you like it all! Isn't that vanity awesome?! The vanity was a table gift from the 2012 GAW "Broadway Glamour " convention held in Livonia, MI. There's a few on eBay now if you like it...let me know if you'd like and I'll find you a link. xoxo It IS a totally cool vanity and I love that it lights up! =)
Awwww Nilsa, you always know justtt the right thing to say!!! Vanessa is beaming now, thank you SO much! xoxox
holy wow!!! love the fashion and this fantastic vanity! where's the vanity from, if you don't mind me asking? it's really amazing!
like her?? are you kidding?
she is gorgeous!!!!!!!!!!!!!!!!!!!!!!!!!!
I loooove her
Find Dolls at Ashton-Drake Galleries
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First they captured the attention of fans with their debut album and singles, and now the first set of One Direction concerts have been announced. Check out the schedule below and then buy your One Direction tickets today!
Event | Location | Venue | Date |
Ever since they placed third on the 2010 UK version of X-Factor, One Direction has emerged as one of the most popular acts of the last few years not just at home, but also around the world. Now One Direction is out on the road by themselves for the very first time and fans are anxiously waiting to hear the band perform. Get your One Direction tickets at TicketNetwork and enjoy seeing the band that's been called the new British invasion.
One Direction was created during the 7th season of the UK version of X-Factor. Niall Horan, Zayn Malik, Liam Payne, Harry Styles, and Louis Tomlinson had tried out as solo candidates but did not qualify for the Boys category and were instead joined together into a band. Though they were one of the more popular acts in the competition, One Direction ultimately placed third during the final week.
After the show ended, One Direction was signed to Simon Cowell's Syco Records and got to work on recording their debut album Up All Night. "What Makes You Beautiful" was released in September 2011 to a #1 spot and was followed up by "Gotta Be You" in November. The full album was also released in November and clocked in at #2 in the UK and at #1 in the United States.
One Direction announced the Up All Night Tour in September of 2011 and prior to their North American dates went on tour with fellow pop band Big Time Rush, which helped jumpstart their popularity in the western hemisphere.


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When we selectively reject science it handicaps us in a knowledge-based global economy.
People are leaving religion but, as they do, and as they become parents, they're facing a difficult question: how, or whether, to talk about religion with their children.
Hemant Mehta points to a great piece where a mother describes how and why her 7 year old daughter has concluded gods don't exist.
Susan Jacoby describes that, despite the impression some have of atheism being a stark colorless position, there are real blessings to be found here when tragedy strikes.
A giant squid has finally been caught on film and the footage is soon to be aired.
Steven Novella on morality, religion, philosophy, and politics.
Turns out nearly half of all sun-like stars may have Earth-like planets.
On the ethics of genetic information. Whole genome sequencing is here and we need the logistics for sharing the results.
Sea-level rise could be way worse than we thought.
Confirmation now of a rogue planet in orbit around "Eye of Sauron" star 25 light years away.
When considering the question of how long the human species will continue into the future the answers aren't all doom and gloom.
None means none. We should be careful as those answering "none" to the question of religious belief would often not describe themselves as agnostics or atheists.
Jerry Coyne wrote this week on the two varieties of atheists who refuse to admit it: extremely liberal clergy and people who refer to themselves as nonreligious but who refuse to use the word atheist.
When it comes to factual knowledge about Mormonism the "nones" score highest.
Rising sea-levels might promote increased volcanism.
On the claim that climate change has halted.
Medical myths: when urban legends kill.
Carl Zimmer on some recent research into the evolutionary origins of venom.
President Obama chooses anti-gay preacher to give the benediction at his inaugural. Public outcry causes preacher to step back.
Astronomers are focusing on a supernova called Mingus to find guidance when it comes to dark energy.
Meanwhile, hints of a new dark force may have been spied in the mash up of two galaxies.
The myth of the value of "anti-oxidants" when it comes to health.
We all know comment trolls on blogs and such suck. But there's science that backs it up.
Jerry Coyne on a recently concludedsummit of Muslims looking into evolution and trying to reconcile the science with theology.
Has the rising numbers of "nones" begun to plateau?
Near-Earth asteroid Apophis buzzes Earth. New measurements tell us whether the asteroid will impact Earth in 2036.
Steven Novella on conspiracy theories and democracy.
New research gives scientists a view of fish climbing Darwin's mountain, evolving.
This incredible video gives you an idea what it would feel like to orbit the Moon. Amazing.
Did prune-y fingers evolve as a way to better grip objects in wet conditions?
When did humans realize there was a connection between sex and pregnancy?
As Australia burns, attitudes to climate change are changing. But is it too late?
Meanwhile, the draft of the US climate report has been released for review and the evidence tells a nasty story.
Thanks again for the wonderful compilation
The recent special edition of Scientific American (Vol. 1 No.1 winter 2013) is called "What makes us Human?" It is completely dedicated to the latest in Evolution and well worth $10.
Great stuff buddy.
When did humans realize there was a connection between sex and pregnancy?
ohhh,..so that's where babies come from !!!
I read most of the story about the 7 year old atheist girl to my mother (a theist). As "recovering catholics," we both enjoyed it quite a bit!
I don't read every Sunday School compilation with a fine-tooth comb, but this is a really nice one. I especially liked the piece by Carolyn Castiglia on why her 7-year-old is an Atheist and why she's okay with that. Pretty inspiring.
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Player Entry
The emotes let you fool around, flirt with someone, laugh with friends and most of all you get to HAVE FUN!!!!!!!!!!! Some of them you must earn or complete a festival dancing lesson quest.
To see which of these emotes your character can perform, type /emotelist in-game.
Pages in category "Emotes"
The following 167 pages are in this category, out of 167 total.
Retrieved from "http://lorebook.lotro.com/wiki/Category:Emotes"


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Iran upgrading nuclear program IAEA
Tehran has reportedly upgraded its nuclear program by adding advanced uranium enrichment facilities and building a plutonium-producing reactor according to the International Atomic Energy Agency (IAEA). The IAEA report reflects the increased international concerns about the potential proliferation dangers it represents as the completion date approaches, the Huffington Post reports. According ...
Barred from poll ex-president Rafsanjani calls Iranian leaders ignorant
Former president Akbar Hashemi Rafsanjani has accused Iran's leadership of incompetence and ignorance just days after he was barred from standing in an election next month, the opposition Kaleme website reported on Thursday.Rafsanjani's comments appeared to add to the political conflict between those loyal to the leadership and opposition groups who have been marginalized since ...
Hot weather and fast does not keep Iranians from Quds Day established by imam Khomeini
Hot weather and fast does not keep Iranians from Quds Day established by imam Khomeini Palestine-Iran, Politics, 8/26/2011 Iran's President Mahmoud Ahmadinejad said today Zionist regime's existence "is not merely a threat to the Palestinian and the entire regional nations, rather its establishment and continued survival contrast interests, independence and dignity of all ...
Ahmadinejad Iran backs restoration of security in Iraq
Ahmadinejad: Iran backs restoration of security in Iraq Iraq-Iran, Politics, 8/26/2011 Iran's President Mahmoud Ahmadinejad said yesterday that the Iran fully backs restoration of security and progress in Iraq, in a meeting with visiting Iraqi deputy chairman of Iraqi Kurdistan administration Nechirvan Barzani. IRNA reported saying "Given historical and cultural affinities ...
Barred from election former president slams Iranian leadership
Former president Ali Akbar Hashemi Rafsanjani has accused Iran's leadership of incompetence and ignorance just days after he was barred from standing in an election next month, the opposition Kaleme website reported on Thursday.Mr. Rafsanjani's comments appeared to add to the political conflict between those loyal to the leadership and opposition groups who have been marginalized since ...
Movie Review
Mercury Rising
"Mercury Rising" has numerous flaws, but there is one that really stands out: its central plot device is unnecessary. That's right. The major aspect of the film, that which is supposed to make it different from other routine government conspiracy / action flicks could be dropped from the beginning, and the movie would turn out exactly the same, if not better. This central device is the fact that a ... ...
On Facebook
UANI Launches Iranian Regime Election Repression Toolkit
Election Repression Toolkit highlights the Iranian regime's use of Western and Asian technology and equipment to stifle political dissent and deny voters basic rights of free expression and protest. Interested parties can ...
National Council of Resistance of Iran Deplores Christian Detentions in Country
The National Council of Resistance of Iran has advocated on behalf of persecuted religious minorities in Iran and has called for the humane treatment of Christians in prison in light of deteriorating conditions in some of the country's most notorious ...
Israel says global pressure has no effect on Iran
Israel's prime minister said Thursday that a new report by the U.N. atomic agency shows that international pressure is having no effect on stopping Iran's suspect nuclear ...
Glencore and Trafigura may have supplied Irans nuclear programme
The Guardian reported in April that Glencore had traded $659m (430m) of goods, including aluminium oxide, with Iran last year .Glencore, which is run by the ...
Israeli leader says UN pressure having no effect on curbing Iranian nuclear program
Britain's Foreign Secretary William Hague, left, listens to Israeli Prime Minister Benjamin Netanyahu during a joint news conference before their meeting in Jerusalem, Thursday, May 23, 2013. (AP Photo/Ronen Zvulun, ...
On the record
Nothing will ever completely replace playing the game I love, however I feel like I'm starting a new adventure and I'm genuinely excited about what lies ahead. I'm fortunate to have been given many opportunities throughout my career and now I feel it's my time to give back.
David Beckham
The world's best known footballer was speaking after formally announcing his retirement.
Hotel Review
London Marriott Park Lane
Having taken the Heathrow Express to Paddinton station (a 15 minute ride, with trains running every 15 minutes), I then ...
Keep readingHave Your Say
Do you take the threat of North Korea seriously?
Iran Herald
Iran Herald | Iran Issues, News from Local & Global SourcesNewspapers the world over strive to provide readers with the ultimate news coverage.
The Iran Herald is no exception.
As an online news service we have advantages over traditional newspapers in that stories can be added and updated 24 hours day.
Our objective is to provide the most comprehensive Iranian news available, from our resources, contracted wire services and an inventory of some thousands of sources comprising newspapers, cable and TV networks, radio stations, public broadcasters, NGOs and others, Iranian news is a priority.
National news comes first. We do however strive to provide a complete news services for our readers. World news headlines top several of our pages, we also provide news on what's happening in business, and in the financial markets.
Whether it's the latest Nikkei 225 reading in Tokyo, the sterling exchange rate in London, or the status of the Nasdaq in New York, whether it's local Iran news, the weather forecast for Iran you'll find it all in the Iran Herald.
From Bam to Tehran, the Iran Herald should be your number one choice for breaking news - local, regional, and national.
- Hashish from India seized in Germany
- Spot-Fixing row Sports Minister says my head hangs in shame today
- ICC withdraws Asad Rauf from Champions Trophy because of spot-fixing allegations
- Pakistani umpire Rauf withdrawn from Champions Trophy
- ESPN lays offs some of its employees to control costsAmendedESPN EmployeeUpdate
- Drone strikes are legal and extend to US citizens as well, says Obama
- Two civilians among 13 dead in Pakistan car bomb
- Kerry holds talks with Israeli and Palestinian officials
- Meeting of Syrian opposition leaders begins in Istanbul
- Taliban influence in Afghanistan to grow Russian agency
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- Iran upgrading nuclear program IAEA
- Barred from poll ex-president Rafsanjani calls Iranian leaders ignorant
- Hot weather and fast does not keep Iranians from Quds Day established by imam Khomeini
- Ahmadinejad Iran backs restoration of security in Iraq
- Barred from election former president slams Iranian leadership


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