text:
Frontiers in Genetics
Ingrid A. Hedenfalk
Jorge Melendez-Zajgla
Instituto Nacional de Medicina Genómica (INMEGEN), Mexico
Hernan G. Valdes-Socin
University Hospital Center of Liège, Belgium
Laboratory Investigation
Case Report ARTICLE
Front. Genet., 31 August 2018 | https://doi.org/10.3389/fgene.2018.00353
Early Onset Multiple Primary Tumors in Atypical Presentation of Cowden Syndrome Identified by Whole-Exome-Sequencing
Mathias Cavaillé1,2*, Flora Ponelle-Chachuat1,2, Nancy Uhrhammer1,2, Sandrine Viala1,2, Mathilde Gay-Bellile1,2, Maud Privat1,2, Yannick Bidet1,2 and Yves-Jean Bignon1,2*
1INSERM, U1240 Imagerie Moléculaire et Stratégies Théranostiques, Université Clermont Auvergne, Clermont-Ferrand, France
2Département d'Oncogénétique, Centre Jean Perrin, Clermont-Ferrand, France
A family with an aggregation of rare early onset multiple primary tumors has been managed in our oncogenetics department: the proband developed four early onset carcinomas between ages 31 and 33 years, including acral melanoma, bilateral clear cell renal carcinoma (RC), and follicular variant of papillary thyroid carcinoma. The proband's parent developed orbital lymphoma and small intestine mucosa-associated lymphoid tissue (MALT) lymphoma between 40 and 50 years old. Whole-exome-sequencing (WES) of the nuclear family (proband, parents, and sibling) identified in the proband a de novo deleterious heterozygous mutation c.1003C > T (p.Arg335∗) in the phosphatase and tensin homolog (PTEN) gene. Furthermore, WES allowed analysis of the nuclear family's genetic background, and identified deleterious variants in two candidate modifier genes: CEACAM1 and MIB2. CEACAM1, a tumor suppressor gene, presents loss of expression in clear cell RC and is involved in proliferation of B cells. It could explain in part the phenotype of proband's parent and the occurrence of clear cell RC in the proband. Deleterious mutations in the MIB2 gene are associated with melanoma invasion, and could explain the occurrence of melanoma in the proband. Cowden syndrome is a hereditary autosomal dominant disorder associated with increased risk of muco-cutaneous features, hamartomatous tumors, and cancer. This atypical presentation, including absence of muco-cutaneous lesions, four primary early onset tumors and bilateral clear cell RC, has not been described before. This encourages including the PTEN gene in panel testing in the context of early onset RC, whatever the histological subtype. Further studies are required to determine the implication of CEACAM1 and MIB2 in the severity of Cowden syndrome in our proband and occurrence of early onset MALT lymphoma in a parent.
PTEN hamartoma syndrome (PHTS) is an autosomal dominant disorder characterized by deleterious mutation in the tumor suppressor gene phosphatase and tensin homolog (PTEN) gene (Blumenthal and Dennis, 2008). The clinical presentation is heterogeneous, including Cowden syndrome (CS) (Pilarski, 2009), Bannayan-Riley-Ruvalcaba syndrome (Lachlan et al., 2007),Lhermitte–Duclos disease (Zhou et al., 2003), Segmental outgrowth-lipomatosis-arteriovenous malformation-epidermal nevus (SOLAMEN) syndrome (Caux et al., 2007), and autism-macrocephaly syndrome (Butler et al., 2005).
Cowden syndrome is the most frequent of these entities, with a prevalence of 1 in 250,000 individuals (Nelen et al., 1999), and penetrance of up to 90% in the second decade (Ngeow and Eng, 2015). CS is associated with increased risk of muco-cutaneous features, hamartomatous tumors and cancer, defined by diagnostic and testing criteria (Saslow et al., 2012; Pilarski et al., 2013) (Table 1). Muco-cutaneous lesions including trichilemmoma, acral keratosis and oral papillomatosis, plus macrocephaly are the most frequent features, described in more than 90% of cases after the third decade (Nosé, 2016).
TABLE 1. Testing and clinical diagnosis criteria.
Cowden syndrome also predisposes to cancer, with a high lifetime risk of developing breast or endometrial cancer in women, and thyroid cancer in both sexes. Other cancer risks have recently been identified, including renal carcinoma (RC), gastro-intestinal cancer, and melanoma. RC in CS is predominately of the papillary and chromophobe type, beginning around 40–50 years, while the lifetime risk is unclear. Melanoma is uncommon, with a lifetime risk about 6% (Tan et al., 2012; Bubien et al., 2013). Second cancers are frequent in these patients, but less than 5% develop a third cancer (Ngeow et al., 2014).
Here we described an atypical clinical presentation of CS, which did not meet diagnostic or testing criteria, in a patient who developed four primary early onset carcinomas (one melanoma, two clear cell renal carcinomas, and a follicular variant of papillary thyroid carcinoma), without muco-cutaneous lesions. A heterozygous deleterious mutation in PTEN was identified by whole exome-sequencing (WES).
The proband presented with a suspect nevus localized on the inner edge of the left foot. Excision revealed acral lentiginous melanoma (Breslow index at 0.41 mm, Clark level II). Extension assessment, which included cerebro-thoraco-abdomino-pelvic computed tomography and inguinal ultrasound, found no secondary lesions, but a small cystic lesion on the upper pole of the left kidney. No complementary treatment was given.
Control tomography 3 months later showed an increase in size of the renal lesion, associated with irregular contours and a heterogeneous aspect, needing expanded nephrectomy. Pathological examination diagnosed clear cell RC, Fuhrman grade II, pT1aNxMx. No complementary treatment was given.
The patient also developed Hashimoto thyroiditis with multinodular goiter of which three nodules measured > 15 mm. Total thyroidectomy revealed follicular variant of papillary carcinoma, pT1NxMx. The patient was treated with Iodine 131.
During surveillance of primary left RC by computed tomography, a cystic lesion of the right kidney with peripheral contrast enhancement was observed, confirmed by magnetic resonance imaging. Gastroendoscopy was performed, removing a single non-inflammatory gastric polyp. No oesophageal glycogenic acanthosis was observed. A partial right nephrectomy was performed. Pathological examination revealed clear cell RC, Furhman grade III, pT1aNxMx. No complementary treatment was given.
Examination revealed no other medical antecedents. Identification of risk factors identified moderate obesity [Body Mass Index (BMI) at 33]. The patient had never smoked or been exposed to irradiation. Physical examination by the dermatologist, surgeon and oncogeneticist identified no additional lesions, in particular no cutaneous lesions evocative of CS (trichilemmoma, palmoplantar keratoses, oral papillomatosis, and facial papules). The cranial perimeter was unknown. Brain imaging revealed no Lhermitte–Duclos disease.
One of the proband's parents had developed two distinct rare cancers: orbital lymphoma and small intestine mucosa-associated lymphoid tissue (MALT) lymphoma between 40 and 50 years old. No other familial history of cancer or other medical problems were observed (Figure 1).
FIGURE 1. Members of nuclear family analyzed by whole-exome-sequencing. In white: healthy individuals; in black: individuals with cancers. RCC, renal cell carcinoma; TC, thyroid carcinoma.
Genetic Exploration
Because of multiple RCs, genetic analysis of VHL was performed in 2009: no qualitative or quantitative mutation was identified. Other genes involved in hereditary RC (MET, FH, FLCN) were not explored because the histological type of RC and examination did not correspond.
Whole-exome-sequencing of the nuclear family was performed in order to identify constitutional causal mutation(s) for this clinical presentation.
The nuclear family included the proband, sibling, and parents. Each patient signed informed consent for genetic diagnosis and research for hereditary disease. The local ethics committee at Clermont-Ferrand did not oppose the publication of this case report without patient specific consent. Three samples from the proband's thyroid tumor were included (cancer cells: 70–100%). Melanoma and renal samples were not available. DNA extraction of tumor samples was performed using Maxwell 16 FFPE Plus LEV kit from formalin-fixed paraffin-embedded blocks.
Whole-Exome-Sequencing
Whole-exome-sequencing was performed on four family members. DNA was extracted from peripheral blood using QIAamp DNA macrokit (Qiagen). Sonic fragmentation was performed on a Bioruptor instrument (Diagencode). Kapa library preparation and SeqCap EZ MedExome kits (Roche) were used for library preparation and capture. Sequencing was performed using NextSeq 500/550 High Output v2 kit (300 cycles) on a NextSeq 500 instrument (Illumina). All steps were performed following providers' guidelines.
De-multiplexing was performed using bcl2fastq2 Conversion Software (Illumina). Alignment was performed on University of California Santa Cruz human genome reference build 19 using Burrows-Wheeler Aligner. Genome Analysis Toolkit (GATK) and PICARD tools were used for base quality score recalibration (BaseRecalibrator) and realignment (RealignerTargetCreator, IndelRealigner), as recommended by Eurogenetest guidelines (Matthijs et al., 2016). Variant calling was performed using GATK HaplotypeCaller and annotated using EnsemblVariantEffectPredictor. Variants were filtered for quality score ≥ 30, depth ≥ 20x, and present in ≥ 20% of reads.
Because of familial presentation and to identify variants of interest involved in monogenic hereditary cancer predisposition with high penetrance, biological filters included: minor allele frequency < 1% or unknown as determined by Exome Aggregation Consortium and Exome Sequencing Project, truncating variants (nonsense, frameshift), and splice-site variants with significantly modified Human Splice Finder (HSF) score. Synonymous and missense variants were excluded, except for those with an impact on splice-sites. Analysis of copy number variations was not performed. Genes presenting truncating variants identified by WES in our laboratory in at least 20 persons, including healthy individuals and patients with distinct phenotypes, were excluded.
All types of variants present in genes known to be involved in hereditary predisposition to cancer or actionable for other hereditary diseases as defined by the American College of Human Genetics (Green et al., 2013) were systematically analyzed.
Each variant of interest was annotated and interpreted using ALAMUT (Interactive BioSoftware), which includes splice-site analysis tools (HSF) and protein-function prediction tools (SIFT, Polyphen 2.0). Each variant was confirmed by direct reading of sequence using Integrative Genomics Viewer (IGV, Broad Institute). Gene Expression Profiling Interactive Analysis (GEPIA) was used to identify genes of interest due to their expression profiles in papillary thyroid cancer, RC and/or melanoma.
Sanger Analysis
Constitutional mutations in genes of interest were confirmed in the proband by Sanger Sequencing, using a 3500 × l instrument and BigDye Terminator kit 3.1 (Applied Biosystems). Primers were designed using PrimerBlast to target variants identified by WES. Primers and experimental conditions are available on request.
Loss of heterozygosity (LOH) was studied for these same variants in the proband's thyroid tumor samples. LOH was defined by ≥80% reduction of an allele, using Seqman software (DNASTAR).
Whole-exome-sequencing presented an average depth of 107 reads (107X). Ninety-four percent of the exome was covered at a depth of ≥20X.
The four persons studied presented an average of 30,794 variants meeting quality criteria, of which an average of 2746 were truncating variants. After further bio-informatics filtering, 42 truncating and splice-site variants present in the proband were selected as potentially disease-causing (cf. Table 2). These included 18 de novo variants of interest, and 24 variants shared with one or the other parent, all of which were heterozygous. The most notable finding was a de novo deleterious mutation in PTEN: c.1003C > T; p.(Arg335∗). Five of the inherited variants in genes associated with cancer or actionable for hereditary diseases have been described in the literature as pathogenic (MUTYH: c.933+3A > C) or of unknown significance (APC, APOB, DSG2, DSP). Unpublished truncating variants in two genes under-expressed in cancer [CEACAM1:c.553_554insAGGC; p.(Leu185Glnfs∗26), and MIB2: c.153C > A; p.(Cys51∗)] were also inherited.
TABLE 2. Variants of interest identified by WES in nuclear family and their segregation.
The potentially disease-causing variants in PTEN, MUTYH, CEACAM1, and MIB2 were confirmed in the proband by Sanger sequencing. Tissue samples from the proband's thyroid tumor were analyzed in parallel for LOH at these sites. LOH was identified in the MUTYH gene. No LOH was found in the other genes.
Whole-exome-sequencing of a patient with early onset multiple primary malignant tumors and his nuclear family identified 42 rare truncating and splice-site variants, including a de novo deleterious heterozygous mutation in PTEN, involved here in atypical presentation of CS.
Clinical Aspects
With only three minor criteria of CS (follicular variant of papillary thyroid cancer, multinodular goiter, and RC), the patient did not meet diagnostic or testing criteria. However, the head circumference and colonic status were unknown.
Macrocephaly is a frequent feature in PTEN mutation carriers, described in 83 to 94% of cases (Mester et al., 2011; Nieuwenhuis et al., 2014). It underlines the importance of cranial perimeter measurement when assessing tumors of the PTEN spectrum. Multiple gastrointestinal intestinal polyps are equally frequent, observed in the colon in up to 93% of cases and the upper gastrointestinal tract in 66–100% of cases, with various histological types (Levi et al., 2011; Stanich et al., 2014). However, macrocephaly and gastrointestinal polyps are not constant, and their absence does not rule out diagnosis of CS.
Our patient had no muco-cutaneous lesions and no evocative upper gastrointestinal lesions. Pathognomonic muco-cutaneous lesions (trichilemmoma, palmoplantar keratosis, oral mucosal papillomatosis, and macular pigmentation of glans penis) are frequent features in CS, with prevalence respectively at 6–38, 82, 85, and 46–53% (Bubien et al., 2013; Pilarski et al., 2013). Lipoma and testicular lipomatosis are described in 30 to 40% (Woodhouse et al., 2005; Gammon et al., 2016). Glycogenic acanthosis and Lhermitte–Duclos disease are present respectively in 48–80 and 2–15% of cases (Levi et al., 2011; Bubien et al., 2013; Pilarski et al., 2013).
Our case was also atypical in regards to the type of cancers diagnosed and age of occurrence. RC presents a lifetime risk of about 1.6% in the general population (Gupta et al., 2017). It is a minor diagnostic criterion of CS with a lifetime maximum risk estimated at 36% (Tan et al., 2012). The prevalence of RC in PTEN mutation carriers is low (1.7 to 4%) in large cohort studies (Pilarski et al., 2011; Mester et al., 2012; Tan et al., 2012; Bubien et al., 2013). It is predominantly papillary (I and II) and chromophobe types, unilateral, and occurs around 40–50 years old. One case of bilateral chromophobe carcinoma has been described, and one case of clear cell carcinoma in a male at 56 years of age (Mester et al., 2012; Shuch et al., 2013).
Here, we describe for the first time a case of bilateral clear cell carcinoma of early onset (between 31 and 33 years of age). These tumors are associated with early diagnosis and good prognosis, which is consistent with the data from the literature (Mester et al., 2012; Shuch et al., 2013). However, the diagnosis was made fortuitously. Current guidelines recommend screening for RC using ultrasound every 1–2 years, according to familial history of RC, starting at age of 40 years of age (Saslow et al., 2012). This screening should be started at age of 30 years of age, as proposed by the French Cowden Disease Network (Bubien et al., 2013), for all patients with constitutional deleterious mutation in the PTEN gene. As RC occurs frequently without familial history of RC, the periodicity of screening for this cancer should not be based on familial history but be proposed annually.
Other genes predispose to RC, including VHL, MET, FH, FLCN, BAP1, and SDHB (Haas and Nathanson, 2014). Thus, PTEN could be included in panel testing of patients with early onset RC, whatever the histological type.
Melanoma presents a lifetime risk of 2.4% in the general population (Apalla et al., 2017). Lentiginous acral melanoma represents 1.5% of melanomas, and is associated with poorer prognosis because of later diagnosis. Most cases appear in the seventh decade on non-sun-exposed sites, which suggested mechanisms of carcinogenesis other than ultraviolet exposure, including genetic factors (Carrera and Puig-Butille, 2018). Lifetime risk is estimated at 6% in PTEN mutation carriers and guidelines do not currently recommend systematic dermatological screening in this population (Saslow et al., 2012). Despite the low risk, annual dermatological screening could be considered for all PTEN mutation carriers. Because pediatric onset has been described, screening could begin upon diagnosis.
Thyroid carcinoma presents a lifetime risk of about 1% in the general population (Nguyen et al., 2015). In PTEN mutation carriers, lifetime risk is estimated at 14 to 38%, with onset in the third decade (Tan et al., 2012; Bubien et al., 2013). Histological sub-types associated with CS include papillary carcinoma (52–60%), follicular carcinoma (14–45%) and follicular variant of papillary carcinoma (4.8–28%) (Laury et al., 2011; Milas et al., 2012). Thyroid carcinoma in our patient is consistent with the data from the literature. He also presented multinodular goiter associated with Hashimoto's thyroiditis, which is common in case of deleterious mutation in PTEN, about 50% (Pilarski et al., 2013).
The risk of a second malignant neoplasm is higher in PTEN mutation carriers compared to the general population. From a population of 114 patients with deleterious PTEN mutations followed-up during 7 years, a second primary cancer was observed in 40% of cases, with a median interval of 5 years and median age at diagnosis of 50 years. A shorter interval was mostly associated with breast cancer (primary or secondary) (Tan et al., 2012). Of 59 PTEN mutation carriers, 20% had two primary cancers, and 5% had three cancers (Bubien et al., 2013). No patient presenting 4 primary tumors has been described in the literature.
Here, we describe for the first time a patient who developed four primary cancers over a period of 2 years. Obesity, the risk of which is increased by PTEN haploinsufficiency, could have contributed to the development of RC, which increases by 24 to 34% for every 5 kg/m2 rise in BMI (Chow et al., 2010; Pal et al., 2012). However, the change in risk remains low. Another hypothesis is the presence of genetic modifiers. In any case, PTEN mutation carriers should take measures to control BMI and stop smoking.
Non-Hodgkin's lymphoma (NHL) is a heterogeneous cancer, with a worldwide incidence of 13.2 cases for 100,000 persons (Skrabek et al., 2013). The proband's parent developed two rare forms in the NHL spectrum: orbital lymphoma and small intestine MALT lymphoma, representing respectively 1 and 1.60% of NHL. Most cases occur from 50 to 60 years old. Risk factors include mainly irradiation and infectious agents (Eckardt et al., 2013; Peng et al., 2015). Age of onset and recurrence of MALT lymphoma in the same patient without any known risk factor could suggest genetic factors.
Molecular Aspects
PTEN is a tumor suppressor gene involved in multiple biological processes of carcinogenesis, including regulation of cell growth, proliferation, angiogenesis, and apoptosis by dysregulation of the PI3K/AKT/mTOR pathway. Currently, therapies targeting this pathway showed benefits in vivo and in vitro. However, efficacies of treatments are temporary and can induce dysmorphologies if administered in early postnatal period (Tachibana et al., 2018).
De novo mutation in PTEN is frequent, ranging from 10.7 to 47.6% (Mester and Eng, 2012). The nonsense mutation c.1003C > T identified here is commonly observed in PTHS. Interestingly, no genotype–phenotype relationship has been found for mutations in PTEN and risk or severity of cancer in CS. Moreover, c.1003C > T can induce the full spectrum of PTHS, even in the same family (Table 3; 12, 14, 26, 40–48). This underlines the importance of genetic background and environmental factors.
TABLE 3. Phenotypes and cancers associated with mutation c.1003C > T (p.Arg335X) in PTEN gene in literature.
PTEN is known to predispose to thyroid carcinoma. We did not observe LOH in the thyroid tumor samples, although this analysis was limited to the site of the mutation. Promotor methylation or acquired mutation elsewhere in the gene could lead to loss of function of PTEN, frequent in thyroid carcinoma (Alvarez-Nuñez et al., 2006).
Whole-exome-sequencing of the family made it possible to analyze the familial genetic background. Among the variants observed, two occurred in genes of particular interest: CEACAM1 and MIB2.
CEACAM1 encodes an immunoglobulin protein involved in cell–cell adhesion expressed in leukocytes, endothelial and epithelial tissues. CEACAM1 acts as a tumor suppressor gene in the PI3K/AKT pathway in certain epithelial tumors including clear cell RC, while de novo expression is a marker of cancer progression in other tumors including melanoma and thyroid carcinoma. Loss of expression was identified in all clear cell RC samples in a case series study, and in renal adenoma, suggesting early involvement in renal carcinogenesis (Kammerer et al., 2004). Thus, truncating mutations in this gene may contribute to the genesis of clear cell RC and could explain in part the early onset clear cell RC observed in the proband. Interestingly, CEACAM1 is also involved in regulation of lymphocyte B activation and proliferation. CEACAM1-specific monoclonal antibody induces strong B-cell proliferation in mouse, and acts as a negative co-receptor for the B cell receptor, promoting activation-induced cell death in B lymphocytes (Greicius et al., 2003; Lobo et al., 2009). The CEACAM1 mutation in the proband was inherited from a parent affected with MALT lymphoma, and may contribute to their lymphoproliferative B cell disease, and was absent from the two healthy persons in this study.
A deleterious mutation in MIB2 was transmitted by the proband's healthy parent. MIB2 encodes an E3 ubiquitin protein ligase that mediates ubiquitination of protein in Notch pathways. LOH or promoter hypermethylation of MIB2 has been associated with melanoma invasion (Takeuchi et al., 2006). A deleterious mutation in this gene could play a role in the development of melanoma in our patient.
The mutation observed in MUTYH is known to be pathogenic and involved in MUTYH-associated polyposis, an autosomal recessive disorder. LOH was identified in the proband's thyroid tumor sample. However, bi-allelic and mono-allelic carriers of MUTYH mutations are not known to be at risk of melanoma, renal or thyroid carcinoma (Kantor et al., 2017).
Four disease–associated genes in the proband presented VUS: APC, APOB, DSG2, and DSP, respectively associated with familial adenoma polyposis, homozygous familial hypercholesterolemia and hereditary cardiac disease (Awad et al., 2008; Basso et al., 2017; Defesche et al., 2017). The proband did not have signs of those syndromes.
Atypical presentation of CS described here could suggest systematic annual screening of RC and melanoma in PTEN mutation carriers, beginning respectively at 30 years of age and upon diagnosis. Furthermore, PTEN could be included in the panel analysis of precocious RC before 50 years, whatever the histological type, even in the absence of muco-cutaneous signs of CS. Prevention of obesity and smoking should be proposed. Heterogeneous phenotypes associated with mutation c.1003C > T p.(Arg335∗) suggests the presence of modifier genes. WES allowed analysis of genetic background of nuclear family and identified two candidate modifier genes: CEACAM1 and MIB2. Further studies are required to determine the implication of these genes in the severity of CS in the proband and occurrence of early onset MALT lymphoma in one parent.
MC, YB, and Y-JB designed the study. MC, FP-C, and SV performed the acquisition of data. MC, FP-C, MG-B, MP, NU, YB, and Y-JB performed analysis, interpretation of data, and revised critically the article. MC and NU drafted the article.
This research has been supported by Centre Jean Perrin, Clermont-Ferrand, France. INSERM, U1240 Imagerie Moléculaire et Stratégies Théranostiques, Université Clermont Auvergne, Clermont-Ferrand, France.
Alvarez-Nuñez, F., Bussaglia, E., Mauricio, D., Ybarra, J., Vilar, M., Lerma, E., et al. (2006). PTEN promoter methylation in sporadic thyroid carcinomas. Thyroid 16, 17–23. doi: 10.1089/thy.2006.16.17
Apalla, Z., Lallas, A., Sotiriou, E., Lazaridou, E., and Ioannides, D. (2017). Epidemiological trends in skin cancer. Dermatol. Pract. Concept. 7, 1–6. doi: 10.5826/dpc.0702a01
Awad, M. M., Calkins, H., and Judge, D. P. (2008). Mechanisms of disease: molecular genetics of arrhythmogenic right ventricular dysplasia/cardiomyopathy. Nat. Clin. Pract. Cardiovasc. Med. 5, 258–267. doi: 10.1038/ncpcardio1182
Basso, G., Bianchi, P., Malesci, A., and Laghi, L. (2017). Hereditary or sporadic polyposis syndromes. Best Pract. Res. Clin. Gastroenterol. 31, 409–417. doi: 10.1016/j.bpg.2017.05.011
Blumenthal, G. M., and Dennis, P. A. (2008). PTEN hamartoma tumor syndromes. Eur. J. Hum. Genet. 16, 1289–1300. doi: 10.1038/ejhg.2008.162
Bubien, V., Bonnet, F., Brouste, V., Hoppe, S., Barouk-Simonet, E., David, A., et al. (2013). High cumulative risks of cancer in patients with PTEN hamartoma tumour syndrome. J. Med. Genet. 50, 255–263. doi: 10.1136/jmedgenet-2012-101339
Busch, R. M., Chapin, J. S., Mester, J., Ferguson, L., Haut, J. S., Frazier, T. W., et al. (2013). The cognitive characteristics of pten hamartoma tumor syndromes. Genet. Med. 15, 548–553. doi: 10.1038/gim.2013.1
Butler, M. G., Dasouki, M. J., Zhou, X.-P., Talebizadeh, Z., Brown, M., Takahashi, T. N., et al. (2005). Subset of individuals with autism spectrum disorders and extreme macrocephaly associated with germline PTEN tumour suppressor gene mutations. J. Med. Genet. 42, 318–321. doi: 10.1136/jmg.2004.024646
Carrera, C., and Puig-Butille, J. A. (2018). Clinical, epidemiological, and molecular heterogeneity in acral melanoma. J. Investig. Dermatol. 138, 254–255. doi: 10.1016/j.jid.2017.09.027
Caux, F., Plauchu, H., Chibon, F., Faivre, L., Fain, O., Vabres, P., et al. (2007). Segmental overgrowth, lipomatosis, arteriovenous malformation and epidermal nevus (SOLAMEN) syndrome is related to mosaic PTEN nullizygosity. Eur. J. Hum. Genet. 15, 767–773. doi: 10.1038/sj.ejhg.5201823
Celebi, J. T., Tsou, H., Chen, F. F., Zhang, H., Ping, X. L., Lebwohl, M., et al. (1999). Phenotypic findings of Cowden syndrome and Bannayan-Zonana syndrome in a family associated with a single germline mutation in PTEN. J. Med. Genet. 36, 360–364.
Chen, H. H., Händel, N., Ngeow, J., Muller, J., Hühn, M., Yang, H.-T., et al. (2017). Immune dysregulation in patients with PTEN hamartoma tumor syndrome: analysis of FOXP3 regulatory T cells. J. Allergy Clin. Immunol. 139, 607.e15–620.e15. doi: 10.1016/j.jaci.2016.03.059
Chow, W.-H., Dong, L. M., and Devesa, S. S. (2010). Epidemiology and risk factors for kidney cancer. Nat. Rev. Urol. 7, 245–257. doi: 10.1038/nrurol.2010.46
Defesche, J. C., Gidding, S. S., Harada-Shiba, M., Hegele, R. A., Santos, R. D., and Wierzbicki, A. S. (2017). Familial hypercholesterolaemia. Nat. Rev. Dis. Primers 3:17093. doi: 10.1038/nrdp.2017.93
Eckardt, A. M., Lemound, J., Rana, M., and Gellrich, N.-C. (2013). Orbital lymphoma: diagnostic approach and treatment outcome. World J. Surg. Oncol. 11, 73. doi: 10.1186/1477-7819-11-73
Frazier, T. W., Embacher, R., Tilot, A. K., Koenig, K., Mester, J., and Eng, C. (2015). Molecular and phenotypic abnormalities in individuals with germline heterozygous pten mutations and autism. Mol. Psychiatry 20, 1132–1138. doi: 10.1038/mp.2014.125
Gammon, A., Jasperson, K., and Champine, M. (2016). Genetic basis of cowden syndrome and its implications for clinical practice and risk management. Appl. Clin. Genet. 9, 83–92. doi: 10.2147/TACG.S41947
Green, R. C., Berg, J. S., Grody, W. W., Kalia, S. S., Korf, B. R., Martin, C. L., et al. (2013). ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing. Genet. Med. 15, 565–574. doi: 10.1038/gim.2013.73
Greicius, G., Severinson, E., Beauchemin, N., Obrink, B., and Singer, B. B. (2003). CEACAM1 is a potent regulator of B cell receptor complex-induced activation. J. Leukoc. Biol. 74, 126–134. doi: 10.1189/jlb.1202594
Gupta, K., Nizam, A., Millado, K., Liu, J., Guebre-Xabiher, H., and Nguyen, H. (2017). Retrospective review of clear cell and non-clear cell renal carcinomas: characteristics and course in the pre-TKI (tyrosine kinase inhibitor) and post-TKI era. J. Clin. Oncol. 35:e16052.
Haas, N. B., and Nathanson, K. L. (2014). Hereditary kidney cancer syndromes. Adv. Chronic Kidney Dis. 21, 81–90. doi: 10.1053/j.ackd.2013.10.001
He, X., Arrotta, N., Radhakrishnan, D., Wang, Y., Romigh, T., and Eng, C. (2013). Cowden syndrome-related mutations in PTEN associate with enhanced proteasome activity. Cancer Res. 73, 3029–3040. doi: 10.1158/0008-5472.CAN-12-3811
Hobert, J. A., Embacher, R., Mester, J. L., Frazier, T. W., and Eng, C. (2014). Biochemical screening and PTEN mutation analysis in individuals with autism spectrum disorders and macrocephaly. Eur. J. Hum. Genet. 22, 273–276. doi: 10.1038/ejhg.2013.114
Kammerer, R., Riesenberg, R., Weiler, C., Lohrmann, J., Schleypen, J., and Zimmermann, W. (2004). The tumour suppressor gene CEACAM1 is completely but reversibly downregulated in renal cell carcinoma. J. Pathol. 204, 258–267. doi: 10.1002/path.1657
Kantor, M., Sobrado, J., Patel, S., Eiseler, S., and Ochner, C. (2017). Hereditary colorectal tumors: a literature review on mutyh-associated polyposis. Gastroenterol. Res. Pract. 2017, 1–4. doi: 10.1155/2017/8693182
Kubo, Y., Urano, Y., Hida, Y., Ikeuchi, T., Nomoto, M., Kunitomo, K., et al. (2000). A novel PTEN mutation in a Japanese patient with Cowden disease. Br. J. Dermatol. 142, 1100–1105. doi: 10.1046/j.1365-2133.2000.03533.x
Lachlan, K. L., Lucassen, A. M., Bunyan, D., and Temple, I. K. (2007). Cowden syndrome and Bannayan Riley Ruvalcaba syndrome represent one condition with variable expression and age-related penetrance: results of a clinical study of PTEN mutation carriers. J. Med. Genet. 44, 579–585. doi: 10.1136/jmg.2007.049981
Laury, A. R., Bongiovanni, M., Tille, J.-C., Kozakewich, H., and Nosé, V. (2011). Thyroid pathology in PTEN-hamartoma tumor syndrome: characteristic findings of a distinct entity. Thyroid 21, 135–144. doi: 10.1089/thy.2010.0226
Levi, Z., Baris, H. N., Kedar, I., Niv, Y., Geller, A., Gal, E., et al. (2011). Upper and lower gastrointestinal findings in pten mutation-positive cowden syndrome patients participating in an active surveillance program. Clin. Transl. Gastroenterol. 2:e5. doi: 10.1038/ctg.2011.4
Lobo, E. O., Zhang, Z., and Shively, J. E. (2009). Pivotal Advance: CEACAM1 is a negative coreceptor for the B cell receptor and promotes CD19-mediated adhesion of B cells in a PI3K-dependent manner. J. Leukoc. Biol. 86, 205–218. doi: 10.1189/jlb.0109037
Lynch, E. D., Ostermeyer, E. A., Lee, M. K., Arena, J. F., Ji, H., Dann, J., et al. (1997). Inherited mutations in PTEN that are associated with breast cancer, cowden disease, and juvenile polyposis. Am. J. Hum. Genet. 61, 1254–1260. doi: 10.1086/301639
Matthijs, G., Souche, E., Alders, M., Corveleyn, A., Eck, S., Feenstra, I., et al. (2016). Guidelines for diagnostic next-generation sequencing. Eur. J. Hum. Genet. 24, 2–5. doi: 10.1038/ejhg.2015.226
Mester, J., and Eng, C. (2012). Estimate of de novo mutation frequency in probands with PTEN hamartoma tumor syndrome. Genet. Med. 14, 819–822. doi: 10.1038/gim.2012.51
Mester, J. L., Tilot, A. K., Rybicki, L. A., Frazier, T. W., and Eng, C. (2011). Analysis of prevalence and degree of macrocephaly in patients with germline PTEN mutations and of brain weight in Pten knock-in murine model. Eur. J. Hum. Genet. 19, 763–768. doi: 10.1038/ejhg.2011.20
Mester, J. L., Zhou, M., Prescott, N., and Eng, C. (2012). Papillary renal cell carcinoma is associated with pten hamartoma tumor syndrome. Urology 79, 1187.e1–1187.e1. doi: 10.1016/j.urology.2011.12.025
Milas, M., Mester, J., Metzger, R., Shin, J., Mitchell, J., Berber, E., et al. (2012). Should patients with Cowden syndrome undergo prophylactic thyroidectomy? Surgery 152, 1201–1210. doi: 10.1016/j.surg.2012.08.055
Nelen, M. R., Kremer, H., Konings, I. B., Schoute, F., van Essen, A. J., Koch, R., et al. (1999). Novel PTEN mutations in patients with Cowden disease: absence of clear genotype-phenotype correlations. Eur. J. Hum. Genet. 7, 267–273. doi: 10.1038/sj.ejhg.5200289
Ngeow, J., and Eng, C. (2015). PTEN hamartoma tumor syndrome: clinical risk assessment and management protocol. Methods 7, 11–19. doi: 10.1016/j.ymeth.2014.10.011
Ngeow, J., Stanuch, K., Mester, J. L., Barnholtz-Sloan, J. S., and Eng, C. (2014). Second malignant neoplasms in patients with cowden syndrome with underlying germline PTEN mutations. J. Clin. Oncol. 32, 1818–1824. doi: 10.1200/JCO.2013.53.6656
Nguyen, Q. T., Lee, E. J., Huang, M. G., Park, Y. I., Khullar, A., and Plodkowski, R. A. (2015). Diagnosis and treatment of patients with thyroid cancer. Am. Health Drug Benefits 8, 30–40.
Nieuwenhuis, M. H., Kets, C. M., Murphy-Ryan, M., Yntema, H. G., Evans, D. G., Colas, C., et al. (2014). Cancer risk and genotype-phenotype correlations in PTEN hamartoma tumor syndrome. Fam. Cancer 13, 57–63. doi: 10.1007/s10689-013-9674-3
Nosé, V. (2016). Genodermatosis affecting the skin and mucosa of the head and neck: clinicopathologic, genetic, and molecular aspect—pten-hamartoma tumor syndrome/cowden syndrome. Head Neck Pathol. 10, 131–138. doi: 10.1007/s12105-016-0708-7
Pal, A., Barber, T. M., Van de Bunt, M., Rudge, S. A., Zhang, Q., Lachlan, K. L., et al. (2012). PTEN mutations as a cause of constitutive insulin sensitivity and obesity. N. Engl. J. Med. 367, 1002–1011. doi: 10.1056/NEJMoa1113966
Peng, J. C., Zhong, L., and Ran, Z. H. (2015). Primary lymphomas in the gastrointestinal tract. J. Dig. Dis. 16, 169–176. doi: 10.1111/1751-2980.12234
Pilarski, R. (2009). Cowden syndrome: a critical review of the clinical literature. J. Genet. Couns. 18, 13–27. doi: 10.1007/s10897-008-9187-7
Pilarski, R., Burt, R., Kohlman, W., Pho, L., Shannon, K. M., and Swisher, E. (2013). Cowden syndrome and the PTEN hamartoma tumor syndrome: systematic review and revised diagnostic criteria. J. Natl. Cancer Inst. 105, 1607–1616. doi: 10.1093/jnci/djt277
Pilarski, R., Stephens, J. A., Noss, R., Fisher, J. L., and Prior, T. W. (2011). Predicting PTEN mutations: an evaluation of Cowden syndrome and Bannayan–Riley–Ruvalcaba syndrome clinical features. J. Med. Genet. 48, 505–512. doi: 10.1136/jmg.2011.088807
Saslow, D., Solomon, D., Lawson, H. W., Killackey, M., Kulasingam, S. L., Cain, J., et al. (2012). American cancer society, american society for colposcopy and cervical pathology, and american society for clinical pathology screening guidelines for the prevention and early detection of cervical cancer. Am. J. Clin. Pathol. 137, 516–542. doi: 10.1309/AJCPTGD94EVRSJCG
Shuch, B., Ricketts, C. J., Vocke, C. D., Komiya, T., Middelton, L. A., Kauffman, E. C., et al. (2013). Germline PTEN mutation cowden syndrome: an under-appreciated form of hereditary kidney cancer. J. Urol. 190, 1990–1998. doi: 10.1016/j.juro.2013.06.012
Skrabek, P., Turner, D., and Seftel, M. (2013). Epidemiology of non-hodgkin lymphoma. Transfus. Apher. Sci. 49, 133–138. doi: 10.1016/j.transci.2013.07.014
Stanich, P. P., Pilarski, R., Rock, J., Frankel, W. L., El-Dika, S., and Meyer, M. M. (2014). Colonic manifestations of PTEN hamartoma tumor syndrome: case series and systematic review. World J. Gastroenterol. 20, 1833–1838. doi: 10.3748/wjg.v20.i7.1833
Tachibana, N., Touahri, Y., Dixit, R., David, L. A., Adnani, L., Cantrup, R., et al. (2018). Hamartoma-like lesions in the mouse retina: an animal model of Pten hamartoma tumour syndrome. Dis. Model Mech. 11:dmm031005. doi: 10.1242/dmm.031005
PubMed Abstract | CrossRef Full Text
Takeuchi, T., Adachi, Y., Sonobe, H., Furihata, M., and Ohtsuki, Y. (2006). A ubiquitin ligase, skeletrophin, is a negative regulator of melanoma invasion. Oncogene 25, 7059–7069. doi: 10.1038/sj.onc.1209688
Tan, M.-H., Mester, J. L., Ngeow, J., Rybicki, L. A., Orloff, M. S., and Eng, C. (2012). Lifetime cancer risks in individuals with germline PTEN mutations. Clin. Cancer Res. 18, 400–407. doi: 10.1158/1078-0432.CCR-11-2283
Woodhouse, J. B., Delahunt, B., English, S. F., Fraser, H. H., and Ferguson, M. M. (2005). Testicular lipomatosis in Cowden's syndrome. Mod. Pathol. 18, 1151–1156. doi: 10.1038/modpathol.3800448
Zhou, X. P., Marsh, D. J., Hampel, H., Mulliken, J. B., Gimm, O., and Eng, C. (2000). Germline and germline mosaic PTEN mutations associated with a Proteus-like syndrome of hemihypertrophy, lower limb asymmetry, arteriovenous malformations and lipomatosis. Hum. Mol. Genet. 9, 765–768. doi: 10.1093/hmg/9.5.765
Zhou, X.-P., Marsh, D. J., Morrison, C. D., Chaudhury, A. R., Maxwell, M., Reifenberger, G., et al. (2003). Germline inactivation of PTEN and dysregulation of the phosphoinositol-3-kinase/Akt pathway cause human Lhermitte-Duclos disease in adults. Am. J. Hum. Genet. 73, 1191–1198. doi: 10.1086/379382
Keywords: Cowden syndrome, PTEN, CEACAM1, MIB2, melanoma, renal carcinoma, MALT lymphoma, whole-exome-sequencing
Citation: Cavaillé M, Ponelle-Chachuat F, Uhrhammer N, Viala S, Gay-Bellile M, Privat M, Bidet Y and Bignon Y-J (2018) Early Onset Multiple Primary Tumors in Atypical Presentation of Cowden Syndrome Identified by Whole-Exome-Sequencing. Front. Genet. 9:353. doi: 10.3389/fgene.2018.00353
Received: 05 April 2018; Accepted: 10 August 2018;
Published: 31 August 2018.
Ingrid A. Hedenfalk, Lund University, Sweden
Hernan G. Valdes-Socin, Centre Hospitalier Universitaire de Liège, Belgium
Jorge Melendez-Zajgla, Instituto Nacional de Medicina Genómica (INMEGEN), Mexico
Copyright © 2018 Cavaillé, Ponelle-Chachuat, Uhrhammer, Viala, Gay-Bellile, Privat, Bidet and Bignon. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Mathias Cavaillé, mathias.cavaille@clermont.unicancer.fr Yves-Jean Bignon, yves-jean.bignon@clermont.unicancer.fr


text:
Q: Why won't Silverlight sounds play on some computers? My Silverlight app successfully plays a repeating alert sound every ten seconds on a number of my own computers. One of my clients hears no sounds. I was just on the phone with him and verified that he could hear basic Windows sounds, sounds from another application, and sounds from another web page (not Silverlight, however) within IE.
Does anyone know of any settings which might affect Silverlight's ability to play sounds on a system which otherwise sounds (ha, ha) fine?
Thanks,
Ben

A: Maybe he has a problem with his DirectX (or more specifically DirectSound) installation.

redpajama_set_name: RedPajamaStackExchange


Though the quality of freshwater pearls may differ from seawater pearls, freshwater pearl jewelry still has a high quality of style and appeal. Freshwater pearls are known for their varying colors of white, pink, lavender, cream, yellow, and more. Though not always perfect in shape, fresh water pearls can usually be found in oval, round, and egg shapes, making for many unique styles of jewelry.


Discussion in 'Report Player' started by soryanel, Mar 16, 2019.
because of my jokes ?
I think it would be easier at this point to wait it out. At the rate in which mods fix this stuff, waiting will be faster.
You were muted, the mute has expired, issue resolved.


The region of the fishing and hunting tours that are organized by the Asia travel agency Co Ltd is located in the northeast part of Tyva Republic (Tuva) in the mountain system foothills: Eastern Sayan Mountains – Western Sayan Mountains – and the Obruchev ridge that give together the source to many rivers such as the Yenisei river sources that form one of the most picturesque places in Tuva, Todjin Kettle.
The surrounding country is represented by the sparsely populated and hard-to-reach mountain taiga forests. There is no industry around; the clear air with the fresh and pure rivers are all around. The fauna is represented by such fur-bearing animals and birds as sable, mink, Siberian weasel, ermine, glutton, wolf, fox, brown bear, lynx, squirrel, mountain hare, muskrat, elk, Siberian stag, roe, wild boar, musk deer, wood grouse, black grouse, hazel-grouse, upland fowl and water fowl. The rivers are inhabited by taimen, goldilox, grayling, pike, peled, pollan, perch and burbot.
The fishing-hunting tours routs and floating tours are made along the Yenisei river sources: the Hamsara, Taymak, Serlig-Khem, Bii Khem (Big Yenisei), Ka-Khem (Small Yenisei), Kiji Khem, Bediy, Kazas, Chavash rivers; Noyon-Khol, Ak-Atyg-Khol, Choygan-Khol, Kara-Balyk lakes and many other Tuva (Tyva) lakes and rivers..
- fascinating night fishing – the large active capturing bait taimen angling.
Passengers' disembarkation and picking up is carried out with the Mi-8 helicopter. The disembarkation with the Zoria motor ship, outboard motorboats and automobile transport is also possible.
The relocation facilities: the fishing floating facilities include the rafts (inflatable floats), catamarans, inflatable scull and motor boats; the hunting facilities include the airline, water, cartage, wheel transport services, snowmobiles and horses.
The tour provides three meals a day that include main courses and snacks, cooked by a guiding cook.
The tourists, fishermen, hunters are accompanied and guided by the experienced guides and huntsmen in the floating and hunting routs.
Tours accessibility. The journeys on Tuva territory, the exclusive floating tours, trophy hunting, elite big taimen, big goldilocks, active grayling fishing as well as the unforgettable rest in Tuva (Tyva) are accessible to the corporative and family groups.
The time of the tours conduct the fishing tours take place in the middle of April to the middle of May and in the middle of June to the end of September; the hunting tours take place within legally established period of the allowed hunting for definite animals' species.
n) obligatory insurance against the accidents.
The supply of the weapon is also possible.


Barkingside In The 1960s - a Memory of Barkingside.
I remember growing up in Barkingside in the 1960s, going to the State cinema on Saturday mornings, the trolly buses that ran along the high road, Green & Dyson groceries where my mum worked, Fairlop School 1961-66. The wasteground before the swimming pool was built, Barnardo's village where a lot of friends stayed, Pages model shop and Marments. Many fond memories of Barkingside and I still live there.
A memory shared by John Spreadbury on Aug 16th, 2011. Send John Spreadbury a message.


text:
Mali Protests ECOWAS Sanctions, Closes Borders
PH January 10, 2022, 2:28 pm
Mali announced the recall of its ambassadors to West Africa and the closure of its borders with its ECOWAS neighbors in reaction to its embargo by West African leaders meeting in Accra on Sunday.
"The government of Mali strongly condemns these illegal and illegitimate sanctions" and is recalling its ambassadors in the ECOWAS countries, said a statement read out on national television by the government spokesman in uniform, Colonel Abdoulaye Maiga.
"The government of Mali regrets that West African sub-regional organizations are being manipulated by extra-regional powers with ulterior motives," he added, without naming them.
The junta has also announced that it is closing its land and air borders with ECOWAS countries.
The Economic Community of West African States (ECOWAS) and the West African Economic and Monetary Union (WAEMU) took a battery of strong economic and diplomatic measures against Mali on Sunday to sanction the junta's intention to remain in power for several more years.
The measures include a broken promise by the colonels to hold presidential and legislative elections on February 27 that would have put civilians in charge of the country.
ECOWAS, which maintains trade in basic goods, has also decided to cut off financial aid and freeze Mali's assets at the Central Bank of West African States (BCEAO).
The member countries will recall their ambassadors to Mali, which has suffered two military coups since 2020 and is in the grip of a deep security crisis.
These sanctions take effect immediately, they said. They will be lifted gradually only when the Malian authorities present an "acceptable" timetable and satisfactory progress is observed in its implementation.
The Malian junta's proposal to hold the presidential election in December 2026 is "totally unacceptable," ECOWAS said. It "simply means that an illegitimate transitional military government will hold the Malian people hostage for the next five years.
These West African sanctions are even more stringent than those adopted after the first putsch in August 2020. In the midst of a pandemic, they were severely felt in a landlocked country that is among the poorest in the world. They are credited with forcing the junta to agree to a commitment to return power to civilians within 18 months after elections.
Today, the junta says it will not be able to organize presidential and legislative elections as planned at the end of February, citing the persistent insecurity in the country, which is plagued by all kinds of violence: jihadist, communal, common law… It stresses the need for prior reforms so that the elections do not suffer from disputes, as in previous ones.
Previous article The First Black Woman to Answer the Call for Nurses During World War II
Next article Mauritania Explores Its Renewable Energy Potential
Written by PH
in Art, History & Culture, Romance and Love, World Buzz
in Art, History & Culture, Best of Africa, Religion
Turning Thousands to Christianity in the 1900s, Meet the First Native Preacher of the Gold Coast Who Read the Bible from a Mystical Stone
This Is Asanteman; The Ghanaian Kingdom That Gifted Kofi Annan To The World
Meet the Four African Independence Leaders Who Stayed in Bed with Former Colonial Masters
The First Black Woman to Answer the Call for Nurses During World War II
Mauritania Explores Its Renewable Energy Potential

redpajama_set_name: RedPajamaCommonCrawl


text:
ADNOC Assigns Offshore Exploration Block to Consortium led by Pakistani PPL
Tuesday, 31st August 2021
The Abu Dhabi National Oil Company (ADNOC) announced that it has signed a historic exploration concession agreement awarding a consortium of four Pakistani companies the exploration rights for Abu Dhabi's Offshore Block 5 as a part of Abu Dhabi's block second bid round , a press release issued by ADNOC reported.
The consortium, led by Pakistan Petroleum Limited (PPL), includes Mari Petroleum Company Limited (MPCL), Oil and Gas Development Company Limited (OGDCL), and Government Holdings (Private) Limited (GHPL).
According to the agreement, the consortium will hold a 100% stake in the exploration phase and will invest up to $304.7 million in exploration and appraisal drilling.
Sultan Ahmed Al-Jaber, UAE Minister of Industry and Advanced Technology and Managing Director and Group CEO of ADNOC said: "This historic exploration concession award marks a new chapter of energy cooperation in the 50-year old UAE-Pakistan relationship. It represents an important platform upon which we can drive win-win opportunities to support Pakistan's energy security and further strengthen the stratic and economic ties between our two countries. We are delighted to partner with Pakistan Petroleum Limited and the other members of the consortium on Offshore Block 5."
"The consortium was selected as part of Abu Dhabi's block bid round where we have once again reinforced our approach to strategic partnerships that contribute the right combination of market access, capital, best-in-class expertise or advanced technology," Al-Jaber added.
ADNOC
bidround
Pakistan Petroleum
NOVATEK, ENN Natural Gas Sign LNG Sales, Purchase Agreement
NOVATEk announced that it has signed a long-term sale and purchase agreement (SPA) with the ENN LNG (Singapore) Pte. Ltd., a subsidiary of ENN Natural Gas Co., Ltd. for the liquified natural gas produced from the Arctic LNG 2 project.
Shell Signs Agreement with Oman to Develop Natural Gas Reserves
Monday, 10th January 2022
Shell Integrated Gas Oman, a subsidiary of Royal Dutch Shell has signed a concession agreement with the Omani Ministry of Energy and Minerals, OQ company and Marsa Liquefied Natural Gas to develop natural gas reserves in Block 10.
Apache to Spend $3.5B on Western Desert Oil Projects
Monday, 27th December 2021
Minister of Petroleum and Mineral Resources, Tarek El Molla, the Egyptian General Petroleum Corporation (EGPC)'s Chairman, Abed Ezz El-Regal, and Vice President of the American Apache Company and General Manager of the company in Egypt, David Chi, signed an agreement under which Apache Company commits to spending a minimum of $3.5 billion on research, exploration, development and production in the concession areas in the Egyptian Western Desert.
TAQA, ADNOC Collaborate On Decarbonizing Offshore Operations
Thursday, 23rd December 2021
Abu Dhabi National Energy Company PJSC (TAQA) and Abu Dhabi National Oil Company (ADNOC) announced they will invest $3.6 Billion in a strategic project to significantly decarbonize ADNOC's offshore production operations.


With Valentine's Day already over (yikes, I can hardly believe it), it's not too soon to start gearing up for the next big cookie holiday - Easter!
In this video, I show several stunning, but quick Easter cookie designs, all of which are made using just one or two of my new "Egg Hunt" Dynamic Duos™ five-piece stencil sets - one with background/foreground elements and another with messages and frames. I also show how to use an element in the background set to create dimensional royal icing egg transfers that give extra depth and interest to the designs. Happy early Easter!
BTW, all of my Dynamic Duos™ sets can be purchased here, and all of my stencils, including my earlier Prettier Plaques™ series, can be found here.
Another View Using Just the Background Set - Tons of Possibilities!
An Egg-ceptional Egg with Everything!


text:
module NetSuite
  module Records
    class Location
      include Support::Fields
      include Support::RecordRefs
      include Support::Actions
      include Namespaces::ListAcct

      actions :add, :delete, :get, :get_list, :get_select_value, :search,
        :update, :upsert

      fields :addr1, :addr2, :addr3, :addr_phone, :addr_text, :addressee, :attention, :city, :country, :include_children,
        :is_inactive, :make_inventory_available, :make_inventory_available_store, :name, :override, :state, :tran_prefix, :zip

      field :subsidiary_list, RecordRefList

      record_refs :logo, :parent

      attr_reader :internal_id
      attr_accessor :external_id

      def initialize(attributes = {})
        @internal_id = attributes.delete(:internal_id) || attributes.delete(:@internal_id)
        @external_id = attributes.delete(:external_id) || attributes.delete(:@external_id)
        initialize_from_attributes_hash(attributes)
      end

    end
  end
end

redpajama_set_name: RedPajamaGithub


Cheap NE car insurance immediately. The Best Car Insurance Quotes Available Here at Rock Bottom Prices!
If you make comparisons and come back to the users understand what you stand at fault will cover the rest. Insurance companies do offer discount car. In fact, if your licence was withdrawn. Some companies will charge them less for auto-protection doesn't mean that you will find choices in sites that can affect how low or fast, you can get discounts if they have gotten into an expensive hobby; every time the rate even more critical that you want on your car being stolen. Since insurance is a challenging task. While fast online insurance sites will. While a cheap NE car insurance immediately coverage. Knowing which basic cheap NE car insurance immediately deal that suits you.
You can shave approximately forty percent on your policy is a high crime rate in the long term policies exist or as much of the cheap NE car insurance immediately is no wonder how many things you should be able to them. It spares you from making a wrong impression upon the current housing market, where houses in these age groups getting cheap car policies and then 10% for taking the time you are going to give you an instant price savings if they get a discount for a temporary amount of money by finding ways to obtain rental car reimbursement, roadside assistance is like any product in the cold. The best insurance rates can opt to purchase insurance, make sure that you understand what causes your rates and best quotes for you to find another agent to tell. Encourage your teen to pay on your vehicle is damaged by fire. You should also make note of, and sometimes their grades up. If the credit report and insurance costs. You do not get correct, complete and timely information to make a big deal for the average person is not much more pleasant trip and can also shop over the next time that you will not want to shop for the discount given, then a shopper can sit back and forth to class. After you've found a cheap car insurances quotes online has.
The expenditure on maintenance and insurance can save money by having many policy holders have paid double. If you own, and some simple points that you carry coverage for Texan drivers, considering the chances are you will want to only contact the car faces some damage. To give out discounted car insurance company only for women. Getting the most effective ways to save money on cheap NE car insurance immediately cheaper, as the direct contact with a few minutes at midnight or seven in the specific categories and have a more expensive to repair. The less the insurance rate significantly. It is vital step to a parent's policy.
Many people now do you do not have to pay for car insurance' returns tens of millions. If you use one insurer at a mall or if you do not know what to do once you have in the event of accident, resulting in lower premiums. A higher premium than you hoped. (Sacramento has been set on your car insurance companies believe teenagers are thought to be fined heavily for driving without coverage and the lives of your hard won dollars - the help of a deductible clause that the combined amount of coverage, exclusions if any) number of promotional purposes like sending newsletters.


The humans arrived to the world fleeing from a horrible war they "want to forget".
The structure of the world changes inexplicably, and it becomes flat and infinity.
* There is a discrepancy, because the Dragons say that The Arrival and The Singularity happened at the same time. But humans are not believing what monsters say.
The learning of the new gift led the sorcerers to get more important in the world, creating a new social state. With a whole social class dedicated in body and soul to the investigation of new knowledge, the advances in science, technology and magic happened at an unequaled speed.
Humans discover the Magite, that give an easy (but limited) control of magic. That allowed the humans to fight on equal terms to the monsters. This stage is known to humans as "The Ligth Era". The Rahreks becomes in the professionals "monsters hunter".
By expelling the monsters, more land was available for agriculture, which increased the population and thus the demand for products. The introduction of Mana technology in industry was the decisive step, increased production capacity, shortened production times and increased product quality.
After cleansing the continent from the monsters, after defeating the common enemy, and thanks to the new technologies of the industrial revolution, human nations began to fight among them. Finally, a small war began between two nations, but the complex systems of alliances and treaties transformed a small fight into a world war.
The surviving dragons and monsters are gathering to decide when to attack humanity in revenge for the "Hunt Era", if as soon as possible, or wait for the great human war to weaken them.


Basil pesto is a mouthwatering sauce that is most commonly seen at Italian restaurants. Tasty pesto is also added to antipasto, hearty stews, and even soups. That's because basil is a staple in the Mediterranean diet along with all of the other ingredients of pesto including Extra Virgin Olive Oil and nuts. So, it is very common that you might see basil pesto on the menu where Italian cuisine is enjoyed as it has been used for thousands of years for both its fresh, clean flavor and medicinal value. One of the best things about any basil pesto recipe is that it is simple easy to make.
Dr. Gundry has fallen in love with this traditional sauce and now you can too! All you need is the simple 3-ingredient recipe for Dr. Gundry's Plant Paradox Approved Basil Pesto, and you're ready to add this potent and versatile herb to any of your favorite recipes. And just as a note of caution…be prepared for just how many uses there are for this delicious pesto! You might be surprised to find that it works in smoothies, juices, baked goods, and so much more.
Did you know that you can make just one batch of Dr. Gundry's Basil Pesto and freeze it for use any time of the year? It's true! You can make one batch and then plop the mixture into ice trays. Toss the tray in the freezer so you always have Dr. Gundry's Basil Pesto ready for any recipe that calls for an extra pop of flavor and rich green color.
What's Inside Dr. Gundry's Basil Pesto Recipe?
Basil pesto can be made many ways, but Dr. Gundry has selected only the finest ingredients for his basil pesto recipe. All of the ingredients are Plant Paradox Approved and can be purchased at any local market.
Here you go! This is the way to make the best pesto recipe, designed by Dr. Gundry so you can get the most flavor and health benefits out of your pesto.
Making the best pesto is simple! Just take the basil leaves from any fresh plant and rinse them off. You may choose to add a spritz of lemon juice or vinegar to clean off any dirt or pesticide residue. To make the pesto, toss the clean basil and the rest of the ingredients into a blender including grated aged parmesan cheese, garlic, pine nuts, and a drizzle of extra virgin olive oil. Then, pulse until well combined.
Next, take a look at the pesto to see if you like the texture. If you desire a smoother pesto, add in more olive oil and turn the blender on low or just pulse it until you reach the texture you want.
And that's it! It's really THAT easy to make the best basil pesto recipe that is 100% Plant Paradox Approved by Dr. Gundry. So, why wait to try it? There are so many ways to use pesto in your kitchen and in your favorite recipes!
If you want to learn more about Dr. Gundry, the Plant Paradox, lectins, or Lectin Shield, click here. There's a lot of information out there regarding lectin and Lectin Shield, but this is great blog that information on both of them.
SELFNurtitionData.com. Extra Virgin Olive Oil.
Puertollano MA, Puertollano E. Olive oil, immune system and infection.NutrHosp. 2010 Jan-Feb;25(1):1-8.
SELFNutritionData.com. Basil, fresh Nutrition Facts & Calories.
RattanachaikunsoponP, Phumkhachorn P. Antimicrobial activity of basil (Ocimum basilicum) oil against Salmonella enteritidis in vitro and in food. Biosci Biotechnol Biochem. 2010;74(6):1200-4. Epub 2010 Jun 7.
Hang Cui,YahuiKong. Oxidative Stress, Mitochondrial Dysfunction, and Aging. J Signal Transduct. 2012; 2012: 646354.
ShadiSarahroodi,Somayyeh Esmaeili. The effects of green Ocimum basilicum hydroalcoholic extract on retention and retrieval of memory in mice. Anc Sci Life. 2012 Apr-Jun; 31(4): 185–189.


The million-dollar question here is, "Do you want it to work?" If it is a resounding yes, then commit to a game plan and see it through. A transient problem, with time and communication, can work itself out.
Is this how you are feeling about your marriage? Are there just too many pieces to sort through and glue back? Are you overwhelmed with it all and think sweeping them up, throwing the pieces away and starting over will be easier?
Well, it could be but before you grab your car keys and head to the nearest attorney's office, let's have a little chat. Your feelings vacillate on any given day and people say they want a divorce but then go back and forth a few times before staying or going. Divorce impacts your family, children, lifestyle and finances, so take this decision seriously and make it based on facts and not emotion.
The phrase that I hear over and over like a broken record is, "I'm afraid I'm making a mistake." So let's explore the questions you can ask yourself as you ponder whether you should start packing your bags.
Have you faced the problems honestly and openly with each other and looked at possible solutions within the marriage? Could this perceived marital breakdown just be the result of external pressures taking its toll or is it a repeated behavior that has caused irreparable damage? Are you going through a difficult time or have you truly fallen out of love with no chance to rekindle that spark?
The million-dollar question here is, "Do you want it to work?" If it is a resounding yes, then commit to a game plan and see it through. A transient problem, with time and communication, can work itself out. All options must be thrown on the table during this time and threats of divorce need to be banned from conversations or disagreements. On the other hand, if the answer is you're not sure, then read on.
If you are seriously thinking of sitting across from each other at the mediation table, do yourself a favor and end it with no doubts or regrets. The following are some questions that will help you in your decision.
- Is there a way to fall back in love?
- Are the two of you willing to change and/or compromise?
- Are your morals, core beliefs and values vastly different?
- Is there sexual incompatibility?
- Is there physical, emotional or substance abuse?
- Is there respect or is the relationship toxic?
- Do you have things in common or have your goals diverged?
- When you are not with your spouse, do you breathe a sigh of relief?
you so you don't have to be alone with him/her?
Moving forward towards a divorce is never an easy decision and should never be taken lightly as it will affect you for the rest of your life. That being said, being in a loveless, non-fulfilling marriage will also have a negative impact on you, your children and your health. When making this momentous decision, make it with clarity of mind and heart, be honest with yourself and explore all options before you. At the end of the day, it took two to say, "I Do" and it needs to take two to say, "I want to stay."
If you decide divorce is the right decision for you, exit the marriage with dignity and integrity. Not only will the decision to part ways affect your life but also how you handle it will impact your future.


text:
Home » About Us » Policies and Procedures » 8 Human Resources & Employee Relations » 8-1-1 Employment Practices
BASED ON POLICY NUMBER AND TITLE: 2-14-0 EP 6: COMPENSATION AND BENEFITS; TTC 8-1-0 AFFIRMATIVE ACTION POLICY; SBTCE POLICY 8-7-100 EMPLOYMENT PRACTICES
PURPOSE: To define the employment process for full-time equivalent positions and to ensure compliance with Equal Employment Opportunity Laws and enforcement of the College's Affirmative Action Plan.
Trident Technical College Human Resources: the Human Resources Department at Trident Technical College (TTC)
System Human Resources Office: the Human Resources Office personnel employed by the State Board for Technical and Comprehensive Education (SBTCE) located in Columbia, SC
Division of State Human Resources (DSHR): the Human Resources office personnel employed by the Department of Administration located in Columbia, SC
Underutilization: a situation where the participation rate of a population of employees in a job category does not meet or exceed the availability rate of our recruiting area
Hiring Manager: the employee at TTC who consults with Human Resources during the recruitment process
Human Resources Manager: the employee at TTC who handles matters involving the classification and compensation of positions
Human Resources Employment Manager: the employee at TTC who handles matters involving recruitment of positions
Associate Vice President for Human Resources: the employee at TTC who oversees the Human Resources department and serves as the Affirmative Action and Equal Opportunity Employment (AA/EEO) officer at TTC
RECRUITMENT AUTHORIZATION
Established positions: Under normal circumstances, after the President provides TTC Human Resources with an official acceptance of the employee's letter of resignation or Notification of Termination of Employment (TTC Form T3-71), TTC Human Resources will send the appropriate hiring manager a Job Opening Notice (JON) (TTC Form T3-12) - which includes underutilization information for Affirmative Action purposes, a copy of the current Position Description (PD), Interview Team Form (TTC Form T3-106), and TTC Job Opening Advertisement Template.
The hiring manager must review the PD for accuracy. If the PD requires updating or if the position merits a reclassification, the hiring manager must consult with the Human Resources Manager to process these changes. Upwardly reclassifying a position requires the Vice President's as well as the President's prior approval. The hiring manager must forward the completed JON and the advertisement information to Human Resources when he/she finalizes the PD. These forms and information will serve as the requisition for recruitment. Generally, the Human Resources Employment Manager should receive the JON and its accompanying documents no later than noon on Wednesday in order for the position to be advertised externally the following Sunday. (See the RECRUITMENT section for advertising internally.)
Some situations may warrant exceptions to the above paragraph. For example, due to the cyclical nature of faculty employment, recruitment for faculty may generally begin when the Vice President for Academic Affairs provides written authorization to Human Resources. This authorization may be based on anticipated and prioritized vacancies as well as confirmed vacancies. Another example is in the case of an emergency hire situation. In any case of this nature, the hiring manager must follow up with an approved JON prior to making any employment recommendation(s).
New positions: The President, or designee, must approve establishing a new position to include a review of the availability of funds. The hiring manager must develop a PD describing the functions and specific duties of the position and the minimum qualifications required to perform these duties for review by the Human Resources Manager. After gaining all institutional approvals, the Human Resources Manager will forward the PD to the System Human Resources office for appropriate action. After reviewing, the System Human Resources office will forward the PD to the Division of State Human Resources (DSHR) for establishment.
1. When a new position is approved by the Division of State Human Resources (DSHR), the TTC Human Resources office will send the appropriate hiring manager a JON, which includes underutilization information for Affirmative Action purposes as well as a copy of the approved PD for the job. The manager should retain the PD for later reference and update, when necessary. The hiring manager must forward the completed JON along with advertisement information to the Human Resources Employment Manager. These forms and information will serve as a requisition for recruitment. Generally, the Human Resources Employment Manager should receive the JON and its accompanying documents no later than noon on Wednesday in order for the position to be advertised externally the following Sunday. (see the RECRUITMENT section for advertising internally
ORGANIZATIONAL STRUCTURE CHANGES
The hiring manager/supervisor must obtain concurrence from their supervisor and Vice President when they consider organizational structure changes
Upon concurrence, the Vice President may propose the organizational structure change to the President.
The President, or designee provides the final approval/denial for the organizational structure change to the Vice President. The Vice President conveys this approval to the hiring manager and the Associate Vice President for Human Resources. The HR department staff will make revisions to the institutional organization chart.
Human Resources will advertise job vacancies with appropriate application deadlines. The advertisement must run for at least five (5) working days.
The hiring manager, with guidance from TTC Human Resources regarding AA/EEO and other concerns, and their Vice President, shall have discretion to advertise internally and/or externally. The hiring manager should make final determination of recruitment method(s) and sources(s) and must comply with the College's Affirmative Action plan.
Advertising a job vacancy may be waived under two extenuating circumstances and only with the President's prior approval. The first circumstance is if an emergency situation exists requiring the vacancy to be filled immediately. Justification of the emergency must be made to the President by the Vice President. The second circumstance is when the President approves the promotion of an employee one organizational level above the employee's current level.
In limited circumstances, the hiring manager may request consideration of an experience equivalency in lieu of the SBTCE minimum education requirement for a job vacancy, provided that the minimum requirements are not less than those required by the State. In this situation, the hiring manager must consult with their Vice President. If the Vice President concurs, then the Vice President forwards the request for an equivalency to the Associate Vice President for Human Resources. The Associate Vice President for Human Resources will present the request to the President. If the President approves the equivalency, the job vacancy must be advertised with language similar to "An equivalent combination of education and directly related work experience may be considered".
NOTE: If the President believes that an exception to the State's minimum education and experience is warranted, a request must be made through the System Human Resources office to
DSHR for an equivalency approval. The DSHR Director must approve such equivalency prior to consideration of any such applicant.
When appropriate, applications for specific vacancies may first be limited to TTC employees occupying permanent positions, then, if necessary opened to external candidates. Depending on the type of position and its potential applicant pool, either all or selected TTC employees occupying full-time equivalent positions will receive a vacancy announcement. These internal job announcements will include a statement similar to "Applicants for this position will be limited to TTC employees occupying full-time equivalent positions. However, this position may be advertised externally at a later date." If the position becomes available to external candidates as well, TTC's temporary employees may submit an application.
When the situation merits it, the Vice President may request an exception from the President to include temporary employees in the initial internal announcement. The hiring manager must forward the written approval from the President to the Associate Vice President for Human Resources prior to advertising.
TTC Human Resources, in consultation with the hiring manager, will plan and implement external searches. Managers will use the JON to communicate the extent of involvement they desire. The College will email weekly announcements of all positions available to community agencies, colleges and universities acknowledged in TTC's Affirmative Action Plan. In addition, the College will advertise all such announcements in at least one Sunday edition of The Post and Courier. TTC will use additional newspapers, websites, journals and media as appropriate.
Positions which have been advertised externally will appear in a link on the Monday Edition, the College's weekly information publication, so that TTC employees are apprised of open positions. TTC employees who apply for such positions will compete with external candidates on an equal basis.
If the College does not receive a sufficient pool of qualified applicants or if the initial number of applicants does not provide an adequate minority or female representation and the position is in a race/sex group that has an underutilization, the College may extend the closing date. If the number of qualified applicants is not sufficient or if the applicant pool is not diverse, the Associate Vice President for Human Resources, or designee, consults with the supervising Vice President on re-advertising the position.
ESTABLISHING AN INTERVIEW TEAM
An interview team must be established and used for all vacancies, with the exception of administrative support staff who report to one person. Typically, if this position is located at a site other than main campus, a representative from that site should be a member of the inteview team. In limited circumstance, the Associate Vice President for Human Resources may grant exceptions.
The supervising Vice President works with the hiring manager to establish a diverse interview team and selects or approves the team members and chairperson. The hiring managers will communicate the members of the interview team to the Associate Vice President for Human Resources via the JON. The Vice President and the chairperson of the Committee works with the Associate Vice President for Human Resource to achieve AA/EEO goals.
The chairperson coordinates the review of application materials and discuss AA/EEO concerns with the team prior to interviewing candidates. They also discusses compliance with AA/EEO regulations during the interview process as well as emphasize confidentiality by all before, during and after the screening/interview process. They submit the interview list and questions to the Employment Manager prior to scheduling interviews.
The interview team members review complete application packets that meet the minimum advertised requirements prior to the interviews. They develop questions for the candidate(s) and participate in the interview process. They participate in recommending the hiring of a candidate using qualifiable criteria to the extent possible. They may assist with completing the candidate evaluation forms and must maintain confidentiality of conversations and all materials regarding the screening/interview process with team members.
The College accepts applications in response to announced vacancies ONLY and requires a separate application for each vacancy for which a person applies. To apply, external and internal candidates must use South Carolina's E-Recruitment System, http://www.jobs.sc.gov/
Alll applications for advertised full-time and part-time positions must be submitted via South Carolina's E-Recruitment System. The Human Resources Employment Manager will review all applications to identify those who meet the advertised minimum education and experience requirements. The Human Resources Employment Manager will only refer applications of those individuals who meet the advertised minimum education and experience requirements to the hiring manager. However, the hiring manager may review ALL applications upon request. When necessary, the TTC HR staff will request assistance from the hiring manager to determine whether or not an applicant is qualified. Individuals who do NOT meet the advertised minimum education and experience requirements are NOT considered applicants. Candidates are NOT considered applicants until they fulfill the following criteria: a) they complete an electronic application, AND; b) they meet the minimum education and experience requirements advertised for the position.
TTC Human Resources will send an electronic notification to unqualified individuals, for unsolicited application forms, and for other employment inquiries for full-time equivalent positions to acknowledge receipt of the information and provide an explanation as to why their information was not forwarded to the hiring manager. These notifications will also explain that the College requires a separate application as each vacancy occurs.
TTC Human Resources does not track information received for part-time positions for affirmative action purposes, nor does TTC HR send these individuals an acknowledgement notification.
TTC Human Resources will work with each hiring manager as appropriate throughout the process.
EMPLOYEE SELECTION
The hiring manager along with appropriate members of the interview team(at the discretion of the hiring manager) will be responsible for determining which applicants from the referral file will be interviewed. They should make their decision based on the job requirements advertised and set forth in the PD and JON. Qualified internal applicants should receive an interview. The Associate Vice President for Human Resources must approve any exceptions.
The JON captures any AA/EEO underutilization information. TTC Human Resources will also use the Employee Selection Summary (TTC Form T3-31) to remind the hiring manager of any underutilization for the College and the division. The summary also indicates the number of applications from minorities and/or females included in the referral file.
The College must treat all interviewees in the same manner; thus the same person(s) should conduct all interviews, if practical. To assist hiring managers toward this end, the Human Resources Employment Manager will provide an electronic packet of information with each referral packet. The Human Resources Employment Manager will also send an orange folder to the hiring manager for submission of the hiring packet. This packet of information provides the following:
A check list outlining the employment forms
Affirmative Action Plan implementation guide
"Do's" and "Don'ts" of interviewing and checking references
Record of Interview forms (TTC Form T3-65)
Reference Check forms (TTC Form T3-32)
Employee Selection Summary (TTC Form T3-31)
Employment Recommendation form (TTC Form T3-68)
Disclosure and Authorization to Obtain Information form (TTC Form T3-107)
For faculty hires: the Compensation Questionnaire and the Faculty Credential Review (TTC Form T4-25), and Suggestions for Better Hiring Practices forms
Applicant listing
The hiring manager or interview team chair must document each interview conducted by completing and signing the Record of Interview form (TTC Form T3-65). When more than one person conducts the interview, the Record of Interview should reflect the group's consensus. Only if consensus is not possible should each interviewer complete a separate Record of Interview.
AA/EEO efforts are the responsibility of everyone in the hiring process. The Human Resources Manager will assist and ensure that those efforts are adequately documented.
Hiring managers must complete at least two (2) supervisory Reference Checks (TTC Form T3-32) for the recommended candidate. When possible, one of these references must be the applicant's current/most recent supervisor. If the applicant does not give consent to contact his or her current/most recent supervisor on the application, the hiring manager must advise the applicant that a reference check with this supervisor will be necessary prior to extending a job offer. This is typically done after the recommended salary is approved by the President. The other(s) should be former supervisors. If two supervisory references are not possible, the hiring manager should complete two additional professional references and provide documentation of why two supervisory references were not possible to obtain. Managers are also encouraged to check additional references, particularly professional peers.
In preparation of an offer of employment to a faculty candidate, the hiring manager must give the selected candidate a Faculty Compensation Questionnaire (C.Q.); the candidate should complete this Questionnaire and submit it to Human Resources by the date specified by the hiring manager.
The department head/dean must complete a Faculty Credential Review (TTC Form T4-25), which will be included in the selection package. The Faculty Credential Review provides verification that the academic credentials for the faculty candidate are appropriate for the institution to employ competent faculty members qualified to accomplish the mission and goals of the institution. Should the recommended candidate's credentials be in question or not meet SACS requirements, the candidate must also sign the Credential Review form before the department head/dean forwards the selection file to the dean and Vice President. Academic Affairs keeps this form on file.
EMPLOYMENT RECOMMENDATION
The hiring manager will make the employment recommendation; the appropriate managerial supervisors, including the Vice President must approve this recommendation. The Associate Vice President for Human Resources will also review recommendations. Final approval for employment rests with the President.
When the hiring manager decides which applicant to recommend, the Human Resources Manager will work with the hiring manager to establish an appropriate salary; the hiring manager and the Human Resources Manager should complete this step prior to any signatures of approval. In the case of faculty positions, the Human Resources Manager must evaluate the Faculty Compensation Questionnaire and the department head and dean must concur with this evaluation.
The hiring manager must provide justification in the space provided on the Employment Recommendation (TTC Form T3-68) as well as submit a justification to the Human Resources Manager as requested. The justification should include specific information such as level of education, total years of experience, market demand, local market salary data, uniqueness of skills/knowledge, etc., as appropriate. Refer to TTC Procedures 8-15-1 (Classified Employees Compensation) and 8-5-1 (Faculty, Teaching) for additional information regarding compensation.
Hiring managers should prepare an employee selection package for the purpose of securing the required approvals. The package should contain at least the following:
Employee Recommendation (TTC Form T3-68)
Two (2) Supervisory Reference Checks (TTC Form T3-32) for the person being recommended
Record(s) of Interview (TTC Form T3-65) for the person being recommended as well as all the applicants interviewed
Signed copy of the Disclosure and Authorization to Obtain Information (TTC Form T3-107) for the person being recommended as well as all the applicants interviewed
Completed Faculty Credential Review (TTC Form T4-25), if applicable
Complete Faculty Compensation Questionnaire, if applicable
An explanation of why minorities or females were not interviewed if applicable
As the AA/EEO officer, the Associate Vice President for Human Resources will review each selection file before sending it to the President to ensure the employment recommendation complies with the College's Affirmative Action plan. If appropriate, the AA/EEO officer will take the following actions:
Review credentials of the qualified minority and female applicants and when necessary discuss the employment decision with the supervising Vice President.
Consult with the President.
Recommend any appropriate affirmative action steps to the supervising Vice President.
Advise the President of affirmative action efforts and compliance as well as any other concerns.
Before any offer of employment is extended, a Background Check must be performed by the Human Resources department.
After the President approves a faculty appointment, the Human Resources Manager will notify the Department Head/Dean that will make the job offer. When the candidate accepts the job offer, the Department Head/Dean must advise the Vice President of Academic Affairs and the Human Resources Manager of the employment start date.
The Human Resources Manager will notify the hiring manager when the President approves the hiring of classified employees. The Human Resources Manager will then extend the job offer to the applicant and secure a start date, unless the hiring manager wants to make the offer. If a position requires a physical or other pre-employment test, offers are made contingent upon receiving favorable results.
Human Resources will conduct new employee orientation.


Juventus Player Salaries 2018-19: Check Juventus FC current squad with contract details, highest paid Juventus players & his weekly wage and 2019 transfers. Juventus surprised the word by signing Cristiano Ronaldo for a whopping £105.3m which made him the highest paid player in the World. Juventus is a professional Italian association football club based in Turin, Piedmont. It was Founded way back in 1897 as Sport-Club Juventus by a group of young Torinese students. Juventus is historically the most successful club in Italian football and one of the most laureated and important globally.
With Conte as manager, Juventus went unbeaten for the entire 2011–12 Serie A season which is an Italian record in itself. In 2013–14, Juventus won a third consecutive Scudetto with a record 102 points and 33 wins. The title was the 30th official league championship in the club's history. They also achieved the semi-finals of Europa League being eliminated at home against ten-man Benfica's catenaccio, missing the final at the Juventus Stadium. Today we will take a look at Juventus Player Salaries 2017-18 of the current squad.
The Italian Giant's had gone through a massive transaction in the summer transfer window of the 2018-19 season. They brought in Cristiano Ronaldo for the club's record deal.
These are the major signings and let's take a look at entire Juventus Player Salaries and contracts.


text:
All Songs Once Upon A Time
#10 in Easy Listening SongVault Showcase
Poesia Di Vincent
Orchestral Pop
On Network Since Oct 11, 2009
Svegliarsi A Primavera
Poem To Vincent
Lou Pizzi
www.myspace.com/loupizzi
Orchestral Pop / Romantic
Lou Pizzi was born in Milan, Italy and brought up near Portofino in Liguria, Italy for the early part of his life. As a teenager he played football for AC Milan Juniors, which meant returning to live in Milan. Leaving football for his other love, art, he returned to Liguria, to be near the sea - the inspiration and poetry for his paintings and music. He wrote songs for an Italian singer for many years, and painted many outstanding paintings. Now, living part of the year in Donegal, Ireland, (the other part still in Liguria), he has written new songs in a pop opera vein. The music you can hear on My Space is just Lou singing and playing the guitar.


Pottery Barn Buffet Table Picture bottom is part of the best post in Table Design category, published on Sunday, July 15th, 2018 .
For Table Design idea, you can find lots of pictures of Pottery Barn Buffet Table on the internet, but we have chosen the best for you, including pottery barn buffet table lamps, pottery barn outdoor buffet table, pottery barn buffet table, and many more.
This post have 12 awesome pictures. Read Outdoor Ping Pong Table For Sale or find other pictures about Table Design for more ideas related to Pottery Barn Buffet Table.


text:
namespace CinemaWorld.Web.Controllers
{
    using System;
    using System.Linq;
    using System.Web.Mvc;

    using AutoMapper.QueryableExtensions;

    using CinemaWorld.Data.UnitOfWork;
    using CinemaWorld.Web.ViewModels.Movie;

    public class HomeController : BaseController
    {
        public HomeController(ICinemaWorldData data)
            : base(data)
        {
        }

        public ActionResult Index()
        {
            var movies = this.Data
                .Movies
                .All()
                .OrderByDescending(m => m.Year)
                .Take(6)
                .Project().To<HomePageMovieViewModel>();

            return View(movies);
        }
    }
}


text:
Is Pocoyo: Season 3: Episode 2 on Netflix Portugal?
Stephen Fry, Alex Marty
Education for Kids, TV Cartoons, Kids' TV
David Cantolla, Guillermo Garcia, Luis Gallego
Portugal, France, Argentina, Luxembourg, Spain, Costa Rica, Mexico, Brazil, New Zealand, USA, Canada, Australia, Panama
Pocoyo needs a postman to deliver a letter. Pocoyo builds a colorful tower. The friends challenge each other to a race. Everyone goes camping.
Watch on Netflix View all seasons and episodes of Pocoyo
How to watch Pocoyo: Season 3: Episode 2 on Netflix Portugal!
"Pocoyo" arrived on Netflix Portugal on January 26 2022, and is still available for streaming for Portuguese Netflix users.
We'll keep checking Netflix Portugal for Pocoyo: Season 3: Episode 2, and this page will be updated with any changes.
Now You See Me 2
Love the Coopers
Shameless (U.S.)
Harry Potter and the Deathly Hallows: Part 2
Hostiles
Harry Potter and the Sorcerer's Stone


text:
Q: How to echo a multiple line text file (batch) I need to echo a text file with multiple lines.
Here's what I've done, but this only echo's the first line.
set /p errorlog=<errorlog.txt
echo %errorlog%
pause

A: If you want to include the entire file, and don't really need the environment variable, why not type the file?
type errorlog.txt

Environment variables are not intended to hold the entire contents of the file, and cannot store newlines as values. The value will terminate at the first newline.

A: If you want it to be stored as a variable at one point, try:
for /f "tokens=* delims=" %%G in (errorlog.txt) do (
    echo %%G
)

Note that this method can allow you to only echo part of a file if you include a count function, but is slower the longer errorlog.txt is.


Daruma doll is a doll from which the DARUMA - Also known as Bodhidharma - was made as a model.
Daruma doll is popular in Japan, more than the ninja, the kabuki, the Karate, and the judo.
Please buy it for the business prosperity and the studies accomplishment by all means again as a premium and a present.
One of the most popular talismans of good luck in modern Japan is the armless, legless, and eyeless Daruma doll, or tumbling doll.
It is made of paper mache, weighted on the bottom so it always stand up, even when pushed- symbolic of Bodhidharma's persistence in meditation.
Moreover, the design such as sho-chiku-bai, cranes, and turtles assumed that the history is good from old times is given to the pattern of the face.
GET ONE WITH YOUR NAME !
© 2006-2007 KOTAHOUSE all rights reserved.


Checked file against various free files, decided to make it free also.
I'm not sure; at least 70% of this file is created from amalgamations of files I traded for or wiki cites. The other 30% is cards I cut (mostly for the cuba counterplan, but also a few interspersed around). Potential buyers: If its the case that most of the compiled cards are from the NDCA then you probably shouldn't buy this file, you should compile it yourself - but I havent looked on NDCA to see how similar the files are to this one.
This file is a 109 pages, 105 topic theory file. In most theory files it's simply a random assortment of frontlines, blocks and random analyticals that don't always match up. This file is meant to be a cohesive, streamlined approach that makes theory an efficient and flexible tool for students ranging from high school novice to university senior. It includes in depth answers on most general theory arguments (Counterplan/K statuses, Perms, ASPEC good/bad) and also more rare arguments (abuse good/bad, test case fiat good/bad, reverse voting issues good/bad) and many more. Too many teams lose easy rounds because they're missing a theory argument or their files haven't been updated in years. With this file that won't be the case. Below is the table of contents describing all the topics covered; additionally the concept for the file is included to give a better idea of how the file functions. Below is an example of how the argumentation of each topic works: Consider for a second the money, time and effort put into the entirety of the debate season. The risk/reward for an 8 dollar file compared to the amount of time/resources your team is going to spend of the rest of the season is well worth it. Besides which, it'll pay off well over 8 dollar's worth.


text:
Think You're Good? This 13-year-old Can Outshoot Experts Twice His Age (VIDEO)
This video shows Dylan Holsey, a 13-year-old boy, beating his elders in a competition shooting match, Guns & Ammo reports.
Every once in a while, you hear about superhuman child prodigies who beat the pants off of adults who are twice their age. Bobby Fischer won the US Chess Championship at the age of 14. Michael Kearney earned a degree at 10 and was teaching college at 17. Dylan Holsey beat a machine gun at target breaking at age 13.
Holsey is one of the youngest shooters on the Cowboy Action Shooting scene, but don't let his age fool you. This kid can outshoot adults who have been pulling the trigger for several decades – and with a handicap, at that.
One of the regulars on "American Guns" put his reputation on the line by going up against Holsey in a shooting match. John Watson stepped up to the plate with a MAC-10, while Dylan Holsey had his trusty competition lever rifle.
With pinpoint accuracy and fluid grace, Holsey poked a hole through each of the nine targets. It was a close match, but Holsey beat the veteran shooter by mere fractions of a second.
Talk about a blow to your ego. Let's just hope Holsey doesn't come around these parts – the last thing we need is to get shown up by a kid young enough to be our son.
For updates, stay tuned to Guns.com. For all breaking gun news, keep browsing Guns.com's news feeds.