text:
Figure. Microdeletions at the distal 16p11.2 region in the present study. The region intersects 9 genes and is flanked by 2 blocks of segmental duplications (SDs). Red lines represent deletions in schizophrenia cases and blue lines represent deletions in control subjects. The double-headed arrows indicate the intervals implicated in the present study (distal 16p11.2 deletion; minimal common region, 28.73-28.95 megabases [Mb], hg18) and the known 16p11.2 copy number variation locus (known proximal 16p11.2 region; minimal common region, 29.56-30.11 Mb). Bp indicates base pair; chr, chromosome; EA, European American; FISH, fluorescent in situ hybridization; GAIN/MGS, Genetic Association Information Network/Molecular Genetics of Schizophrenia Consortium; hg, human genome; RefSeq, Reference Sequence collection; and WTCCC2, Wellcome Trust Case Control Consortium 2.
Guha S, Rees E, Darvasi A, et al; Molecular Genetics of Schizophrenia Consortium; Wellcome Trust Case Control Consortium 2. Implication of a rare deletion at distal 16p11.2 in schizophrenia. JAMA Psychiatry.. Published online January 16, 2013. doi:10.1001/2013.jamapsychiatry.71.
eMaterial 1. Samples, genotyping methods and quality control (QC) for the replication cohorts
eMaterial 2. Distal 16p11.2 probe coverage
eMaterial 3. Estimating the selection pressure against the distal 16p11.2 deletion
eMaterial 4. Members of the Molecular Genetics of Schizophrenia Consortium
eMaterial 5. Members of the Wellcome Trust Case Control Consortium 2
eFigure 1. z-Score histogram for distal 16p11.2 in the Bulgarian trio data
eFigure 2. Principal component analysis PCA plot for the Ashkenazi discovery cohort
eFigure 3. 16p11.2 region
eTable 1. Previous observations of distal 16p11.2 deletions
eTable 2. Phenotypic data on carriers of 16p11.2 distal deletions
eTable 3. Publications used to estimate the selection pressure (s) operating against deletions at distal 16p11.2
eTable 4. CNVs in the Ashkenazi Jewish (AJ) and Bulgarian (BG) cohorts at loci previously implicated in schizophrenia
eReferences Diagnostic performance of serological tests – test combinations
Customize your JAMA Network experience by selecting one or more topics from the list below.
Guha S, Rees E, Darvasi A, et al. Implication of a Rare Deletion at Distal 16p11.2 in Schizophrenia. JAMA Psychiatry. 2013;70(3):253–260. doi:10.1001/2013.jamapsychiatry.71
© 2022
Author Affiliations: Division of Psychiatry Research, The Zucker Hillside Hospital, Glen Oaks, New York (Drs Guha, Kane, A. K. Malhotra, and Lencz); Medical Research Council Centre for Neuropsychiatric Genetics and Genomics and Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, Wales (Mr Rees and Drs Ivanov, Owen, O'Donovan, and Kirov); Department of Genetics, The Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel (Dr Darvasi); Fujita Health University School of Medicine, Toyoake, Japan (Drs Ikeda and Iwata); Psychiatric and Neurodevelopmental Genetics Unit, Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School (Drs Bergen and Purcell), and Center for Human Genetics Research, Massachusetts General Hospital (Drs Bergen and Purcell), Boston, Massachusetts; Stanley Center for Psychiatric Research, Broad Institute, Cambridge, Massachusetts (Drs Bergen, Moran, and Purcell and Ms Chambert); Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden (Drs Magnusson and Hultman); Department of Psychiatry, Trinity College Dublin (Drs Cormican, Morris, Gill, and Corvin), and Health Research Board (Dr Walsh), Dublin, Ireland; Institute of Human Genetics (Drs Cichon, Nöthen, and Degenhardt and Mr Priebe) and Department of Genomics, Life and Brain Center (Drs Cichon and Degenhardt and Mr Priebe), University of Bonn, and German Center for Neurodegenerative Diseases (Dr Nöthen), Bonn, Germany; Institute of Neuroscience and Medicine, Research Center Juelich, Juelich, Germany (Dr Cichon); IST/High Performance and Research Computing, University of Medicine and Dentistry of New Jersey, Newark (Dr Rosenfeld); Robert S. Boas Center for Human Genetics and Genomics (Drs Lee and Gregersen) and Center for Psychiatric Neuroscience (Drs Kane, A. K. Malhotra, and Lencz), The Feinstein Institute for Medical Research, Manhasset, New York; Department of Psychiatry, Hofstra University School of Medicine, Long Island, New York (Drs Kane, A. K. Malhotra, and Lencz); Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany (Dr Rietschel, Mr Breuer, and Ms Strohmaier); Division of Psychiatric Genomics, Department of Psychiatry, Mount Sinai School of Medicine, New York, New York (Mr Ruderfer and Drs Purcell and Sklar); Department of Psychiatry and Behavioral Sciences, NorthShore University HealthSystem Research Institute, Evanston, Illinois (Drs Sanders and Gejman); Department of Psychiatry and Behavioral Sciences, University of Chicago, Chicago, Illinois (Drs Sanders and Gejman); National Cancer Institute, Bethesda, Maryland (Dr Shi); Virginia Institute for Psychiatry and Behavioral Genetics (Dr Kendler) and Department of Psychiatry (Dr Riley), School of Medicine, Virginia Commonwealth University, Richmond; Department of Psychiatry, Queens University, Belfast, Ireland (Dr O'Neill); Beyster Center for Genomics of Psychiatric Diseases, University of California, San Diego, La Jolla (Drs D. Malhotra and Sebat); Departments of Genetics, Psychiatry, and Epidemiology, University of North Carolina at Chapel Hill (Dr Sullivan); Stanley Institute for Cognitive Genomics, Woodbury Genome Center, Cold Spring Harbor Laboratory, Cold Spring Harbor, Cold Spring, New York (Mr McCarthy); and Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California (Dr Levinson).
Group Information: Pablo V. Gejman, MD, takes authorship responsibility for the Molecular Genetics of Schizophrenia Consortium, and Aiden Corvin, MRCPsych, PhD, takes authorship responsibility for the Wellcome Trust Case Control Consortium 2.
Context Large genomic copy number variations have been implicated as strong risk factors for schizophrenia. However, the rarity of these events has created challenges for the identification of further pathogenic loci, and extremely large samples are required to provide convincing replication.
Objective To detect novel copy number variations that increase the susceptibility to schizophrenia by using 2 ethnically homogeneous discovery cohorts and replication in large samples.
Design Genetic association study of microarray data.
Setting Samples of DNA were collected at 9 sites from different countries.
Participants Two discovery cohorts consisted of 790 cases with schizophrenia and schizoaffective disorder and 1347 controls of Ashkenazi Jewish descent and 662 parent-offspring trios from Bulgaria, of which the offspring had schizophrenia or schizoaffective disorder. Replication data sets consisted of 12 398 cases and 17 945 controls.
Main Outcome Measures Statistically increased rate of specific copy number variations in cases vs controls.
Results One novel locus was implicated: a deletion at distal 16p11.2, which does not overlap the proximal 16p11.2 locus previously reported in schizophrenia and autism. Deletions at this locus were found in 13 of 13 850 cases (0.094%) and 3 of 19 954 controls (0.015%) (odds ratio, 6.25 [95% CI, 1.78-21.93]; P = .001, Fisher exact test).
Conclusions Deletions at distal 16p11.2 have been previously implicated in developmental delay and obesity. The region contains 9 genes, several of which are implicated in neurological diseases, regulation of body weight, and glucose homeostasis. A telomeric extension of the deletion, observed in about half the cases but no controls, potentially implicates an additional 8 genes. Our findings add a new locus to the list of copy number variations that increase the risk for development of schizophrenia.
Uncovering the genetic factors underlying schizophrenia (SZ) has proven difficult despite heritability estimates of up to 80%.1 Copy number variations (CNVs) at several loci show consistently replicated evidence for association with SZ.2,3 These CNVs are individually very rare, are not fully penetrant, and are found cumulatively in approximately 2% of SZ cases; therefore, large samples were required to establish their association. Given their low baseline frequency, further CNV susceptibility loci likely have yet to be discovered.
In the present study, we report the identification of a CNV locus at distal 16p11.2 that increases the risk for SZ. Findings pointing to a possible association between this locus and SZ were obtained independently by 2 teams of investigators. During the process of obtaining replication data, the 2 groups became aware of each other's work and decided to combine results from their discovery and replication cohorts. Using high-resolution microarrays, one group (from New York and Israel) examined an SZ case-control cohort from the Ashkenazi Jewish (AJ) population, whereas the other group (from Cardiff, Wales) examined a cohort of parent-offspring trios from Bulgaria (BG). Because of the need for large-scale replication, we contacted research groups worldwide who were willing to share raw data from microarray-based CNV studies in cohorts of SZ cases and controls and obtained data from a total of approximately 34 000 individuals.
The final sample (after quality control [QC]) consisted of 662 BG offspring with all their parents in 638 families (615 families with 1 offspring, 22 families with 2, and 1 family with 3). Details on this cohort have been previously described,4 but that previous publication reported on de novo CNVs only; here we report on the transmitted CNVs in this cohort. This cohort does not include patients with severe developmental disorders (all probands had attended mainstream schools, from which people with known intellectual disabilities were excluded). Diagnoses were made according to DSM-IV criteria,5 using an interview from the Schedules for Clinical Assessment in Neuropsychiatry6 and a review of hospital discharge summaries. We included patients with SZ or schizoaffective disorder. Concomitant medical conditions were not systematically assessed except as related to psychiatric diagnosis. The CNVs found in the parents of each trio but not transmitted to the affected offspring constituted the pseudocontrol population listed in the Table under the control headings.
All samples were genotyped on a single-nucleotide polymorphism array (Affymetrix 6.0; Broad Institute). Analysis was performed using software from the manufacturer (Affymetrix Genotyping Console 4.0 software; Broad Institute) one batch at a time, with each batch containing 70 to 90 arrays. The QC process included removal of CNVs if they were from the X or Y chromosome, were less than 15 kilobases (kb), were covered by fewer than 15 probes, or had a probe density (size/probe number) greater than 7500 base pairs. We used the PLINK tool, version 1.07,8 to exclude CNVs if 50% or more of their length was covered by a segmental duplication (SD). Copy number variation loci with a frequency of greater than 1% were excluded. Individuals with multiple large duplicate CNVs on the same chromosome were excluded because these duplications are likely to be artifacts.9 Samples were also removed if their total number of CNVs was very high and constituted an outlier for the distribution within that sample (>50 CNVs for this experiment).
For additional QC of the BG trios, we used a modification of the median z -score outlier detection algorithm proposed by McCarthy et al10 in 2009 and described in detail by Kirov et al4 in 2012. A z score is the median of the standardized log2 ratios for all probes within a specified chromosomal region. Through comparison of all individual z scores for a given region, true CNVs are represented as outliers from the normal distribution of the z scores. We show the distribution of the z scores for the 16p11.2 distal region in eFigure 1, which demonstrates that the only outliers for this region are the 2 probands with deletions and their parents.
Case (n = 1156) and control (n = 2279) samples were selected from an AJ repository (Hebrew University Genetic Resource; http://hugr.huji.ac.il). Patients for the discovery analysis were recruited from hospitalized inpatients at 7 medical centers in Israel. All diagnoses were assigned after direct interview using the Structured Clinical Interview,11 a questionnaire with inclusion and exclusion criteria, and cross-references to medical records. Chronic medical disorders and conditions were recorded on the basis of patient report and hospital records. The inclusion criteria specified that subjects had to be diagnosed as having SZ or schizoaffective disorder by DSM-IV criteria,5 that all 4 grandparents of each subject were reported to be of AJ ethnic origin, and that each subject or the subject's legal representative had signed the informed consent form. Exclusion criteria included any psychotic disorder due to a general medical condition, substance-induced psychotic disorder, pervasive developmental disorders, or any cluster A (ie, schizotypal, schizoid, or paranoid) personality disorder. Samples from healthy AJ individuals were collected from volunteers at the Israeli Blood Bank; these subjects did not undergo psychiatric screening but reported no chronic disease and were taking no medication at the time of the blood draw. Corresponding institutional review boards and the National Genetic Committee of the Israeli Ministry of Health approved the studies. All samples were fully anonymized immediately after collection, and genomic DNA was extracted subsequently from blood samples through the use of a commercially available kit (Nucleon; Pharmacia). Genotyping and analyses were performed under protocols approved by the institutional review board of the North Shore–Long Island Jewish Health System.
Genotyping was performed with commercially available arrays (HumanOmni1-Quad; Illumina, Inc) according to the manufacturer's specifications for approximately 1.4 million genome-wide markers (approximately 900 000 single-nucleotide polymorphisms [SNPs] and 500 000 CNV intensity probes). The SNPs were filtered on the following basis: call rate of less than 98%, minor allele frequency of less than 0.02, and Hardy-Weinberg exact test results of P < .000001 in controls. Samples were filtered on the basis of genotype QC filtration (sample call rate, <97%, sex mismatch) and examined for cryptic identity and first- or second-degree relatedness using the pairwise identity-by-descent estimation in the PLINK tool set8 with 128 403 linkage disequilibrium pruned (r2 > 0.2) genome-wide SNPs. Samples were excluded based on a pairwise identity-by-descent estimation of greater than 0.125; the individual with the lower call rate from each control-control or case-case pair was excluded, and controls were excluded from case-control pairs. The remaining samples were further examined for underlying population stratification using principal component analysis with ancestry informative markers specific for the AJ population.12 Samples with principal component analysis results suggestive of 1 or more non-AJ grandparents were identified as outliers on the basis of a first principal component score greater than 0.01 and were excluded from further analysis (eFigure 2). After QC based on SNP markers, the data set contained 2544 samples consisting of 904 cases (573 male and 331 female) and 1640 controls (1216 male and 424 female) who underwent genotyping on 762 372 high-quality SNPs with a 99.8% overall call rate.
Normalization and log ratio data calculation for 904 cases and 1640 controls were performed using the manufacturer's software platform (GenomeStudio; Illumina, Inc). The resulting log R ratios and B-allele frequencies were used to identify CNVs on autosomes for each subject. We used variations of 3 algorithms for CNV detection: PennCNV,9 QuantiSNP,13 and cnvPartition (http://www.illumina.com). QuantiSNP and PennCNV are based on the hidden Markov model, and cnvPartition is based on bivariate Gaussian distribution as implemented on the manufacturer's software platform (http:// www.illumina.com).
Following the methods of Need et al14 and Sanders et al,15 we excluded any individuals with a PennCNV threshold of log R standard deviation of at least 0.30, B-allele frequency drift of at least 0.002, and/or waviness factor deviating from 0 by greater than 0.04. Individuals containing more than 500 CNVs (before filtration described in the following paragraphs) were also excluded from the analysis. The final data set contains 790 cases and 1347 controls.
We further excluded CNV calls on the basis of the QC thresholds recommended by each of the respective algorithms. Thus, CNV calls were excluded from further analysis if the log Bayes factor was no greater than 10 in QuantiSNP, if the confidence threshold was no greater than 35 in cnvPartition, or if default QC parameters in PennCNV were not obtained.
After the QC steps, all the CNV calls were merged using the CNVision program.15 The final rare CNV calls were based on consensus calls from all 3 algorithms (with no more than 25% of the length drawn from 1 algorithm only), with the following filtration criteria: at least 20 probes, at least 100 kb in size, and less than 1% frequency in the total sample. Copy number variations of the same type (ie, deletion or duplication) that were separated by at least 3 probes were merged into 1 contiguous segment as recommended by Vacic et al.7 All CNVs were annotated using the CNVision program. Based on previous findings in SZ and other neuropsychiatric disorders,16 purely intergenic CNVs were excluded.
Evidence for replication of the findings was obtained from 8 case-control samples recruited and genotyped by other teams from the United States, Europe, and Japan. These samples consisted of 12 398 cases and 17 945 controls who underwent genotyping with high-resolution arrays. Details on the samples, genotyping platforms, and QC used by these teams are specified in eMaterial 1. The minimally affected region was covered well by all arrays used by the other teams (eFigure 3).
All coordinates in this study are based on the Human Genome Build NCBI36/hg18.
After stringent QC procedures, 790 cases and 1347 controls from the AJ cohort and 662 probands from 638 BG families were examined for rare large CNVs. Replication was sought in other case-control data sets for any CNVs that were observed in at least 2 cases and no controls (for the AJ cohort) and transmitted at least twice with no nontransmissions in the BG trios cohort. Several relevant CNVs were found in the 2 discovery data sets at loci already reported to increase the risk for development of SZ; because they are already known susceptibility factors, however, we only list them in eTable 4. In the AJ cohort, CNVs at 2 additional loci were observed in 2 cases and no controls. These loci were at chromosome 6q14.3 (hg18 coordinates: 85.25-85.58 megabases [Mb]) and 7q33 (133.39-133.50 Mb), but replication evidence was not observed. No other CNV of this type was supported by replication evidence in the BG data (apart from the 16p11.2 deletion). The lists of all rare and large (>100 kb) CNVs in the 2 samples that intersected genes are available as files on request from the authors (AJ SZ CNVs >100 kb.xls and BG SZ trio CNVs >100 kb.xls).
The only CNV of interest that overlapped between the 2 discovery samples was a deletion at the distal region of 16p11.2, with a minimal common region extending from 28.73 to 28.95 Mb (build 36, hg18). This region intersects 9 genes and is flanked by 2 SD blocks (Figure). The region does not overlap the known 16p11.2 locus at 29.56 to 30.11 Mb that has been implicated in SZ,10,16 autism,15,17 and developmental delay.18 Deletions at this locus were found in 2 cases (and no controls) from the AJ cohort and 2 offspring from the BG samples, both transmitted from mothers (parents transmitted this CNV in every trio). Duplications at this locus were observed in 1 AJ control and in 1 BG parent (who transmitted it to an affected offspring).
We sought evidence for association between this deletion with SZ in 8 independent case-control cohorts (12 398 cases and 17 945 controls) for which we had access to the raw data (Table and eMaterial 1). Deletions overlapping this region were observed in an additional 9 cases and 3 controls (P = .018, 1-tailed Fisher exact test for the replication sample; odds ratio, 4.35 [95% CI, 1.18-16.06]). Combining the discovery and replication cohorts, we found 13 deletions among 13 850 cases (0.094%) and 3 among 19 954 controls (0.015%) (P = .0014, 2-tailed Fisher exact test; odds ratio, 6.25 [95% CI, 1.78-21.93]). The positions of the CNVs are shown in the Figure. No excess of duplications in cases was found at distal 16p11.2.
The minimal common region for all deletions reported in the Table encompasses 9 genes within a 220-kb interval flanked by blocks of SD (Figure). Some CNVs extend over the SDs (however, we noted that no CNV in the 16p11.2 region was excluded on the basis of >50% overlap with an SD). Different break points that extend over the flanking SD regions (but do not reach the telomeric region that is free of SDs) are more likely to reflect the different coverage of arrays (eMaterial 1 and eFigure 3) and/or the problems of calling CNVs over repetitive regions rather than different pathogenicity, especially because these regions have fewer genes. Seven deletions cover an additional region of unique DNA sequence at the telomeric side (Figure, the interval free of SDs) that contains further genes. Evidence of pathogenicity of the 7 CNVs that extended over the telomeric region was nearly as strong as for the implicated critical region (7 of 13 850 cases vs 0 of 19 954 controls, P = .0019, 2-tailed Fisher exact test). However, the critical distal 16p11.2 region remains the more likely candidate owing to its confirmed involvement in other neurodevelopmental disorders discussed in the "Comment" section and the lack of isolated CNVs in the smaller telomeric region. Of the 3 controls with deletions, 1 (in the Swedish data set) was recruited at the age of 45 years and had type 2 diabetes mellitus and high blood pressure but no other medical or psychiatric problems. No further information is available on the 2 anonymized controls from the Wellcome Trust Case Control Consortium 2/Irish data set; one is from the British Blood Transfusion service (therefore presumably healthy), and the other is from the 1958 cohort.
The new distal locus is approximately 600 kb telomeric from the previously implicated proximal 16p11.2 CNV (29.56-30.11 Mb).10 The CNVs at proximal 16p11.2 have been shown to increase risk for SZ, autism, and developmental delay when duplicated5,16 and for autism and developmental delay when deleted.10,15,18 None of the CNVs in our study extend over the proximal region (Figure).
We have previously demonstrated that the known SZ-associated CNVs have high mutation rates and that strong selection pressure operates against them.19 We can estimate the de novo rate for this deletion at 25% based on the present study (2 transmitted deletions and no information on inheritance in the other subjects) and 4 available data sets with a total of 5 de novo occurrences of 20 events with a known inheritance20-23 (eMaterial 1 and eTable 3). This rate approximates to a selection pressure of 0.25. In line with this, we observe the 2 BG proband deletions to be found on different haplotypes and therefore very likely to be independent mutations.
Phenotypic data, where available, indicate a spectrum of typical presentations of SZ with no evidence of intellectual disability or a specific clinical profile (eTable 2). This indication is similar to the lack of specific clinical presentations reported for the other large CNVs implicated in neurodevelopmental disorders.2,15,20 The possible exception is the presence of 2 individuals with obesity and 2 with type 2 diabetes mellitus (plus 1 control with type 2 diabetes mellitus) in line with previous reports. In addition to the 13 cases listed in the Table and eTable 2, the brother of 1 case (in the Japanese sample) carries the same deletion and also has SZ. Further probands had positive family histories of SZ, but we do not know whether their affected relatives also carry the deletion. Although the transmission status of the CNVs is only available for the BG cohort, we further note that both deletions were transmitted maternally.
Several lines of evidence from the literature support the distal 16p11.2 deletion as a true SZ-associated CNV locus. The deletion has been implicated in developmental delay and other clinical phenotypes18,20,21 (details are given in eTable 1), similar to other SZ-associated CNVs.2,3,10 Briefly, Cooper et al18 reported a very similar increased rate of 0.1% (15 of 15 767) for this deletion in children with intellectual disability, autism spectrum disorders, and congenital malformations who were referred for genetic testing compared with a control rate of 0.01% (1 of 8329). Similar rates were found in another large study on patients with developmental delay and a range of other abnormal phenotypes20: 31 of 23 084 cases (0.13%) and 1 of 7700 controls (0.01%). Of the 6 cases in that study for whom detailed clinical information was available, one had autism, behavioral problems, attention-deficit/hyperactivity disorder, and SZ; another had behavioral problems, attention-deficit/hyperactivity disorder, and bipolar disorder; and a third had autism. Four of these 6 cases were overweight and all 6 had developmental delay. Moreover, additional telomeric extension of the deletion (to approximately 28.4 Mb) was present in 9 of the 31 cases and was never observed in the controls. Similarly, in our study, 7 of the 13 cases demonstrated this telomeric extension, which was not seen in the controls. The controls used in these studies partially overlap ours, so these control rates are not independent (eTable 1). Additional published reports of distal 16p11.2 deletions include 5 patients from 2 separate families,22 all of whom have developmental delay and behavioral problems, and 1 child of 4284 patients with mental retardation.23
Distal 16p11.2 deletions have also been shown to be enriched in patients with severe early-onset obesity (3 of 300 [1%]) compared with unscreened population controls (2 of 7366 [0.03%]),21 consistent with the findings in the study by Bachmann-Gagescu et al.20 The most likely obesity candidate within the distal 16p11.2 region was postulated to be SH2B1 because this gene plays a role in the regulation of body weight and glucose homeostasis in mice.24 Two of our cases were obese or overweight, and 2 cases and 1 control had type 2 diabetes mellitus (consistent with being overweight, although this information is not available). However, 1 carrier (from Japan) had documented evidence of normal weight, and several did not have recorded evidence of obesity despite being drawn from cohorts that were assessed for this and other medically relevant phenotypes.
Considerable heterogeneity of phenotypic expression has been reported for most large rare CNVs implicated in SZ, with carriers often manifesting nonpsychotic phenotypes, including intellectual disability, autism, epilepsy, obesity, and cardiac disorders.2,16 Pleiotropy appears to also be the case for distal 16p11.2 deletions, possibly owing to the presence of multiple genes within the deleted region.
Clinical presentations for distal 16p11.2 deletion carriers are unremarkable for SZ, with diagnoses ranging across all major subtypes: paranoid, catatonic, undifferentiated, and schizoaffective. The age at SZ onset for deletion carriers ranges from 15 to 30 (mean age, 23.4) years, with no clear evidence of early onset. Two parents who transmitted the deletions to probands did not have psychotic disorders, although one had a mood disorder. Of the 3 controls who carry the deletion, one (from Sweden) did not report psychiatric problems at age 45 years, which is past the usual accepted age for the period of risk for SZ. Of the other 2 controls, one had also passed through the risk period (from the 1958 cohort, examined at age 44-45 years [ eMaterial 1]) and the third one, a blood donor, is presumably healthy and not receiving any medication. These observations indicate that this CNV does not have full penetrance, similar to most other CNVs implicated in SZ. None of the carriers had any other SZ-associated CNVs.
Mutations in several of the 9 genes within the critical region of distal 16p11.2 have been implicated in neurological diseases. Homozygous mutations in the gene TUFM have been described in infants with fatal encephalopathy25; ATP2A1 is implicated in Brody disease, in which patients are unable to relax their muscles during exercise,26 and its homologue, ATP2A2, has been implicated in neuropsychiatric phenotypes.27 In addition, ATXN2L (although unknown in function) encodes a protein belonging to the spinocerebellar ataxia family. The remaining genes are involved in immunity or in insulin and leptin signaling (SH2B1) or are of unknown function. In addition to the 9 genes in the minimal critical region, the larger CNVs with telomeric extensions include 8 additional deleted genes (7 of them in a DNA region that is free of SDs [Figure]), possibly increasing the pathogenicity of these larger CNVs. Most notable among these 8 genes is CLN3, for which recessive mutations are associated with Batten disease, characterized by childhood-onset neurodegeneration.28 Moreover, CLN3 is the only gene in the minimal or the extended region that is implicated in synaptic function on the basis of Gene Ontology annotation. Our previous study of de novo CNVs indicated an enrichment of such genes in SZ-related events; however, CLN3 is not among the postsynaptic density genes implicated in that study.4 Additional evidence from animal knockout models may help disentangle the contributions of each of these genes to the observed range of phenotypes.
In conclusion, we have obtained strong evidence of the role of a new CNV locus in SZ. Similar to other such loci, it is very rare and increases the risk for other neurodevelopmental phenotypes.
Correspondence: Todd Lencz, PhD, Division of Psychiatry Research, The Zucker Hillside Hospital, 75-59 263rd St, Glen Oaks, NY 11004 (email@example.com); George Kirov, PhD, MRCPsych, Medical Research Council Centre for Neuropsychiatric Genetics and Genomics and Neuroscience and Mental Health Research Institute, Cardiff University, Heath Park, Cardiff CF4 4XN, Wales (firstname.lastname@example.com).
Submitted for Publication: May 31, 2012; accepted July 19, 2012.
Published Online: January 16, 2013. doi:10.1001/2013.jamapsychiatry.71
Author Contributions: Dr Guha and Mr Rees contributed equally to the research. Drs Lencz and Kirov contributed equally to the research. Drs Guha, Lencz, and Kirov and Mr Rees take full responsibility for the integrity of the data.
Conflict of Interest Disclosures: None reported.
Funding/Support: Work at Cardiff University was supported by grant G0800509 from the Medical Research Council Programme and Centre Grants, grant 2 P50 MH066392-05A1 from the National Institute of Mental Health (NIMH), and grant EU-GEI from the European Union. Genotyping was funded by multiple grants to the Stanley Center for Psychiatric Research at the Broad Institute from the Stanley Medical Research Institute, the Merck Genome Research Foundation, and the Herman Foundation. The Zucker Hillside Hospital work was supported by the North Shore–Long Island Jewish Health System Foundation and grants RC2 MH089964 (Dr Lencz), R01 MH084098 (Dr Lencz), P50 MH080173 (Dr A. K. Malhotra), and P30 MH090590 (Dr Kane) from the National Institutes of Health. Molecular Genetics of Schizophrenia Consortium data collection was supported by R01 grants MH67257, MH59588, MH59571, MH59565, MH59587, MH60870, MH59566, MH59586, MH61675, MH60879, and MH81800 and U01 grants MH46276, MH46289, MH46318, MH79469, and MH79470 from the NIMH. We acknowledge support through Young Investigator Awards (Dr Sanders and Jubao Duan, PhD) from the National Alliance for Research on Schizophrenia and Depression and from the Genetic Association Information Network, the Paul Michael Donovan Charitable Foundation, and the Walter E. Nichols, MD, and Eleanor Nichols endowments (Stanford University). Genotyping performed by the Center for Genotyping and Analysis at the Broad Institute of Harvard and Massachusetts Institute of Technology was supported by grant U54 RR020278 from the National Center for Research Resources. The German study was supported by grants 01GS08144 and 01GS08147 from the German Federal Ministry of Education and Research (BMBF), within the context of the Integrated Genome Research Network MooDS (Systematic Investigation of the Molecular Causes of Major Mood Disorders and Schizophrenia). Control data were provided by the community-based studies of PopGen (Population-based Recruitment of Patients and Controls for the Analysis of Complex Genotype-Phenotype Relationships), Cooperative Health Research in the Region Augsburg, the Heinz Nixdorf Recall study, and MooDS. Genotyping of Wellcome Trust Case Control Consortium 2 samples was funded by grants 085475/B/08/Z and 085475/Z/08/Z from the Wellcome Trust. The British 1958 Birth Cohort DNA collection was funded by grant G0000934 from the UK Medical Research Council and grant 068545/Z/02 from the Wellcome Trust, and the UK National Blood Service controls by the Wellcome Trust. The Japanese cohort was supported in part by research grants from the Japan Ministry of Education, Culture, Sports, Science and Technology; the Ministry of Health, Labor and Welfare; the Core Research for Evolutional Science and Technology; and the Health Sciences Foundation (Research on Health Sciences focusing on Drug Innovation).
Role of the Sponsors: The sponsors had no role in the design and conduct of the study; in the collection, analysis, and interpretation of the data; or in the preparation, review, or approval of the manuscript.


text:
We offer family dental services in the Verona, WI community!
Dr. Matt and his staff pride themselves on providing excellent care to all of our patients. We offer a full range of services for you and your family. We've recently invested in the equipment needed to perform even more dental services in the office. With our added technology, there are very few things that we cannot handle at our location.
Our office has a comfortable, inviting atmosphere. We strive to make your experience a welcoming, enjoyable one. We look forward to you becoming part of our dental family!
Please contact us today to schedule an appointment!

subset: commoncrawl


text:
Here are seven conference teams that could play like the offseason has already begin as they close out the .the automotive category there is nothing I can comment on right now that is definitive.Letourneau was impressive her win over Maryna Moroz but what she does best is what Jedrzejczyk is the best at.Hingle USA TODAY Sports A source said that at least one other team was willing to give Brees $60 million guaranteed over two years to try and woo him away from New http://www.authentictampabayrayshops.com/Sergio-Romo-Jersey Orleans.
Today the series continues with the 2017 Hurricanes.He preferred to be out the yard playing sports.has been on the team's president for only a few days, but already he didn't like what he saw Tuesday night when Latrell Sprewell returned to Square Garden with curses and taunts a Minnesota Timberwolves' victory that dropped New 's record to 10.
Because of the volume of reader comments, we cannot review individual moderation decisions with readers.the 23-year-old winger rebound after his benching?Simply put, did not give a .For the second straight year, NFL player jumped into a Salvation Army kettle during a Cowboys game at AT&T Stadium.That's probably going to dog him until he gets back on the mound.
Yes, Johnny Manziel was awful on .Led http://www.vegasgoldenknightsofficialonline.com/Adidas-William-Carrier-Jersey the team with 996 snaps played.The NFL is infamously conservative, but it is also a league of evolution.1 Alabama against No.
Also, a lot depends on Jianlian's ability to step out and lead this year's team throughout group stage.He's well-rounded and dominant.Where are they getting this stuff?He became the school's first FBS All-American a year ago, earning third-team honors 2016.Stone now has 18 goals and 24 assists on the .
The Chargers William Carrier Jersey insist they have full confidence their game plan no matter who is under center.'t say I didn't warn you.is involved, all of the key marketing Sergio Romo Jersey partners.It's pretty cool to be the guy they waste a franchise tag on, because you've only got one.


text:
Nebulizer Medication Bottle
Capitalizing upon our tremendous years of experience, we are offering our treasured clients a high quality Nebulizer Medication Bottle. Offered bottle is precisely manufactured using the best quality raw materials and modern machinery under the supervision of our knowledgeable professionals. Ideal in patients of bronchitis and asthma, the bottle provided by us helps in efficient respiratory therapy. Also, this bottle is precisely checked on defined quality parameters to assure its flawlessness. Clients can avail this Nebulizer Medication Bottle from us at rock-bottom prices.
CHANGZHOU ZHENGYUAN MEDICAL TECHNOLOGY CO. LTD. All Rights Reserved.(Terms of Use)
Developed and Managed by Infocom Network Private Limited.


text:
Gateway ID47H07u
Average of 3 scores (from 3 reviews)
Reviews for the Gateway ID47H07u
Source: PC Mag
Unless WiMAX is a must for you, the Gateway ID47H07u offers a ton of features in a handsome, highly portable chassis for a pleasingly low price. Its bid to topple the Dell Inspiron 14z (Core i5) for Editors' Choice honors is thwarted only by our subjective impressions of its keyboard and touchpad, plus the Dell's backlit keyboard and removable battery.
Single Review, online available, Very Short, Date: 12/30/2011
Rating: Total score: 80%
Source: Techreview Source
Battery life is above average in our tests as we were able to get about 7 to 7.5-hours of juice out of it while the category average is about 5.5 to 6 hours.
Single Review, online available, Very Short, Date: 12/05/2011
Rating: Total score: 80%
Source: Laptop Mag
The updates to the Gateway ID47H07u made a good notebook even better. This classy 14-inch system has even more power and endurance than before, and its Dolby-powered speakers are also top-notch. However, the glossy touchpad isn't for everyone. We prefer the HP dm4t, which has a better touchpad, fingerprint reader, and a larger hard drive for $50 less. But if you want Core i5 power, all-day endurance, and a sleek design at a reasonable price, this Gateway laptop is a good deal.
Single Review, online available, Short, Date: 11/29/2011
Rating: Total score: 80%
Intel HD Graphics 3000: Integrated graphics card in the Intel Sandy Bridge processors (Core ix-2xxx). The HD 3000 is the faster (internally GT2 called) version with 12 Execution Units (EUs).
Only some 3D games with very low demands are playable with these cards.
» Further information can be found in our Comparison of Mobile Graphics Cards and the corresponding Benchmark List.
2430M: Dual-core processor based on the Sandy Bridge architecture with an integrated graphics card and dual-channel DDR3 memory controller. The CPU is clocked at 2.4 GHz (Turbo Boost 2.7-3 GHz) and the GPU at 650 (1200 MHz Turbo).» Further information can be found in our Comparison of Mobile Processsors.
Above all, this display size is used for subnotebooks, ultrabooks and convertibles. For all three types, this size is quite large. The biggest variety of subnotebooks is represented with this size.
Large display-sizes allow higher resolutions. So, details like letters are bigger. On the other hand, the power consumption is lower with small screen diagonals and the devices are smaller, more lightweight and cheaper.» To find out how fine a display is, see our DPI List.
2.1 kg:
Usually subnotebooks, ultrabooks and quite lightweight laptops with 12-16 inch display-diagonal weigh as much.
Gateway: Gateway, Incorporated. is a computer hardware company based in California which develops, manufactures, supports, and markets a wide range of personal computers, computer monitors, servers, and computer accessories. AOL acquired Gateway.net, the online component of Gateway Inc., in 1999. 2007, Acer completed its acquisition of Gateway for approximately US$710 million. The market share outside of the US market is rather low.
In 2014 to 2016, Gateway did no longer belong to the Top 10 laptop manufacturers/distributors. Newer devices from Gateway are hardly reviewed by specialist media any longer (as of 2016).
80%: This rating is not convincing. The laptop is evaluated below average, this is not really a recommendation for purchase.
» Further information can be found in our Notebook Purchase Guide.


text:
Summary | Excerpt | Reading Guide | Reviews | Beyond the book | Readalikes | Genres & Themes | Author Bio
Summertime is an inventive and inspired work of fiction that allows J.M. Coetzee to imagine his own life with a critical and unsparing eye, revealing painful moral struggles and attempts to come to grips with what it means to care for another human being.
A young English biographer is researching a book about the late South African writer John Coetzee, focusing on Coetzee in his thirties, at a time when he was living in a rundown cottage in the Cape Town suburbs with his widowed father - a time, the biographer is convinced, when Coetzee was finding himself as a writer. Never having met the man himself, the biographer interviews five people who knew Coetzee well, including a married woman with whom he had an affair, his cousin Margot, and a Brazilian dancer whose daughter took English lessons with him. These accounts add up to an image of an awkward, reserved, and bookish young man who finds it hard to make meaningful connections with the people around him.
Summertime is an inventive and inspired work of fiction that allows J.M. Coetzee to imagine his own life with a critical and unsparing eye, revealing painful moral struggles and attempts to come to grips with what it means to care for another human being. Incisive, elegant, and often surprisingly funny, Summertime is a compelling work by one of today's most esteemed writers.
22 August 1972
In yesterdays Sunday Times, a report from Francistown in
Botswana. Sometime last week, in the middle of the night, a
car, a white American model, drove up to a house in a residential
area. Men wearing balaclavas jumped out, kicked down
the front door, and began shooting. When they had done with
shooting they set fire to the house and drove off. From the
embers the neighbours dragged seven charred bodies: two men,
three women, two children.
The killers appeared to be black, but one of the neighbours heard them speaking Afrikaans among themselves and was convinced they were whites in blackface. The dead were South Africans, refugees who had moved into the house mere weeks ago.
Approached for comment, the South African Minister of Foreign Affairs, through a spokesman, calls the report unverified. Inquiries will be undertaken, he says, to determine whether the deceased were indeed South African citizens. As for the military, an unnamed ...
Though it may strike an odd note of praise, the most admirable quality of J.M. Coetzee's Summertime is the author's monastic restraint. As the novel develops through a disjoint series of interviews with characters from the early career of the now famous writer J.M. Coetzee, practically every page calls out for the real Coetzee to break the fourth wall of narration and intervene on his hapless hero's behalf. No such intrusion is forthcoming. Instead, we play rapt audience to lovers, family and colleagues whose recollections painstakingly depict the fictional Coetzee as a calamitous failure of a human being, unable to make contact through the walls of his genius... More than just an academic exercise in meta-fiction, this is an understated yet riveting portrait of the artist as a young man...continued
Full Review
(567 words).
This review is available to non-members for a limited time. For full access, become a member today.
(Reviewed by Micah Gell-Redman).
Born in Cape Town, South Africa, on February 9, 1940, J. M. Coetzee* studied first at Cape Town, earning degrees in English and mathematics. He worked for several years as a computer programmer while he researched his thesis on the novelist Ford Madox Ford. In 1968 he graduated from the University of Texas at Austin with a PhD in English, linguistics, and Germanic languages. His dissertation was on the early fiction of Samuel Beckett.
After three years as an assistant professor at SUNY Buffalo, his application for permanent residence in the U.S. was denied as a consequence of his anti-Vietnam war activism. In 1972 he returned to South Africa and joined the faculty of the University of Cape Town where he held a series of positions until ...
This "beyond the book" feature is available to non-members for a limited time. Join today for full access.
More books by J M Coetzee
If you liked Summertime, try these:
In Philida, longlisted for the Man Booker Prize, André Brink"one of South Africa's greatest novelists" (The Telegraph)gives us his most powerful novel yet; the truly unforgettable story of a female slave, and her fierce determination to survive and to be free.
Nicole Krauss has written a soaring, powerful novel about memory struggling to create a meaningful permanence in the face of inevitable loss.
and discover exceptional books
for just $3.75 per month.
A Minor Chorus
A debut novel from a rising literary star that brings the modern queer and Indigenous experience into sharp relief.
Solve this clue:
and be entered to win..
Your guide toexceptional books
BookBrowse seeks out and recommends the best in contemporary fiction and nonfiction—books that not only engage and entertain but also deepen our understanding of ourselves and the world around us.


text:
Large Financial Company Licensing. Join with one of these Agencies
DFI makes use of the NMLS to control all Mortgage Broker licenses. Make application and all sorts of modifications to a home loan Broker license through the NMLS.
Before You Apply
Review the documents below to help make a decision that is informed the Mortgage Broker License.
Before applying, you have to obtain particular registrations, licenses, and pass an assessment requirement outside DFI.
Testing Requirement
Application Procedures
Certain what to be prepared or gathered include:
More info: For assistance on publishing an application, see: Submitting Company Form Quick Guide
Sponsor home loan Originator In the event that business is mortgages that are originating Mortgage Loan Originator is necessary, therefore sponsor them now: See: MLO Sponsorship Quick Guide
Our Loan Providers
Does your large financial company gain access to all the banking institutions? We could make use of professional loan providers unavailable to the majority of agents.
Our Mission, Vision & Values
As you of Australia's leading professional home loans, we should be the ideal at everything we do. Nevertheless we also provide a reason that is great be successful.
Our Systems, People & Training
Find out about the way the mortgage loan Specialists' market systems that are leading technology, individuals & training provide us with an advantage on the competition.
Our Team
Find out more about this true mortgage loan kind here.
Prepare To Get System
Do you want buying a residential property within the next couple of years? Our home loans can evaluate your position & enable you to prepare to have authorized!
Priority Service With Banks
Priority service with banks offers mortgage that is certain faster turnaround times on mortgage loan applications. Does your broker get VIP therapy?
What Exactly Is A Home Loan Broker?
They are able to help you to get authorized for a mortgage, negotiate a great rate of interest while making the application procedure simple exactly what is a home loan broker precisely?
Why an expert is needed by you
Steer clear of the pitfalls & don't danger getting declined! Our lenders understand how to get your mortgage loan approved. Talk with a specialist today!


text:
Editor's Note: Robert R. Reilly, former senior advisor for information strategy for the U.S. Secretary of Defense and special assistant to President Ronald Reagan, spoke to LifeSiteNews about his newest book, Making Gay Okay: How Rationalizing Homosexual Behavior Is Changing Everything, published by Ignatius Press. The full interview is below and our report on the interview is here.
If it is said that "two people become one flesh when they get married," how does the Supreme Court deal with the fact that two men can't become one? Does the Supreme Court think that they become one with each other?
This is part of the judicial shell game that has allowed the courts to substitute homosexual "marriage" for marriage. But one has to ask the question: How can homosexuals consummate a marriage and, if they can't, how can it be a marriage? This is a key issue because, for many hundreds of years, common law held that a marriage must be consummated in order to be valid. If it were not consummated, it could be declared a nullity. Consummation meant then, and has always meant, vaginal intercourse. It could not possibly have meant sodomy because sodomy was a crime in common law. Sodomy was forbidden in all of the American colonies and, until fairly recently, in all 50 states.
How did the courts get around this? Simply by ignoring it. How do they get away with it? Unfortunately, American culture some time ago separated sex from diapers. The essential procreative side of sex has been suppressed. Once this has been done, there is no reason even to require that sex be unitive. This crazy logic led the Massachusetts Supreme Court in Goodridge v. Department of Public Health to declare that the act of consummation is irrelevant to marriage. This goes against more than a 1000 years of jurisprudence. Only unitive sex can be generative, and generative sex has to be unitive. Once you deny this and remove it from marriage, the whole thing falls apart and sex becomes a toy or an emotive outlet. Anything can then be called marriage. But sex apart from the unitive and generative is obviously not spousal.
How did our current situation in America around homosexuality and same-sex "marriage" develop? And what are your suggestions to get us back to normalcy?
The most immediate cause was the sexual revolution in the 1960s that separated sex from diapers. If heterosexuals can rationalize their sexual misbehavior, why can't homosexuals rationalize theirs? The deeper cause has been the overthrow of the "Laws of Nature and of Nature's God" as a source of moral meaning. We no longer have to respect the inbuilt purposes in Nature because we deny that they exist. We pretend that we get to make up our own purposes. Reality is based upon our will and power, not upon what is. We do this to satisfy our appetites. We don't want to conform to reality; we want reality to conform to us. Therefore, we rationalize our sexual misbehavior by turning evil into good. (To illustrate these two fundamentally different views of reality, I use Aristotle and Jean-Jacques Rousseau in the book.)
We saw two totalitarian ideologies in the 20th century that were based upon variations of this belief in the will to power and the denial of the laws of nature. If reality is based upon will, then the person with the strongest will gets to rule. This ineluctably leads to tyranny. Those two ideologies eventually crashed and burned, as all such denials of reality eventually do. The problem is that they created a huge amount of damage in the interim.
This new ideology of the will that is being imposed upon us now is only beginning to exercise its hegemony. The phase of enforcement has begun. How can our society remain sane and accept these new rulings? This reminds me of Germany in 1935 with the passage of the racist Nuremberg laws. No doubt, there were still many fine and moral people in Germany, but for the most part they acceded to the pseudoscientific, racist dictates of the Nazi regime. The denial of reality in which we are now involved is just as profound. However, we are in better shape because the principles of the American regime are still there to be appealed to, even if they are ignored. We are, after all, founded upon "the Laws of Nature and of Nature's God." We need to rescue their meaning. Perhaps a new American Revolution will be required. It can be a peaceful one, but it requires resistance and recovery.
How do kids know if they are gay/lesbian at so young an age? Do they understand fully what it actually means?
They don't. It's a farce. It is being enforced upon them. The violation of children's innocence spread through these teachings simply shows that the homosexual movement will not allow anything to stand in the way of the rationalization of its sexual misbehavior. If the price for that is children's innocence, too bad for them.
Are the teachers pressuring the kids to become gay/lesbian? And are the teachers being told to do so?
It is becoming part of the curriculum and is required in several states. Take a look at the Gay, Lesbian, and Straight Education Network (GLSEN) and see where its materials are used in elementary and high schools. It has spread like wildfire. Classroom presentations by homosexuals, or on the subject of homosexuality, are invitations to obscenity and inevitably lead to the question: "How do you guys do it?" The response is usually, "We are not allowed to talk about our personal sex lives." Nevertheless, with the question implanted, curious young minds will ineluctably be drawn to the subject of sodomy. "So that's what those nice guys who talked with us do? There must not be anything wrong with it!" Mission accomplished—to make the abnormative normative before the children have developed their critical faculties of thought. Of course, it's much worse in high schools where very explicit instructions are given in deviant sex and how to "protect" oneself when engaging in it.
Why are the parents of children being shut up when they complain about their child being taught about gay sexual activities in schools at age 7? Do they not have a say just like the gay/ lesbians?
Here is a sample of what has happened, and a model for more to come. In 2008 in Massachusetts Dr. Paul B. Ash, the superintendent of Lexington Public Schools, announced the "new, formalized diversity curriculum in preparation for the next year, when we plan to pilot 4 to 5 short units in each elementary grade. Some units will focus on families, including families with single parents, foster parents, and gay and lesbian parents." A parent, Shawn Landon, protested, demanding "prior notification to any discussion, education, training, reading or anything at all related (even remotely) to homosexuality".
Here is part of Dr. Ash's response to the father: "Perhaps you are not aware of the lawsuit decided by the United States Court of Appeals (Parker vs. Hurley). This case established Lexington's right to teach diversity units, including stories that show same gender parents. The court decided we are not required to inform parents in advance of teaching units that include same gender parents or required to release students when such topics are discussed. The Appeals Court dismissed the claim that parents have a right to require the school to provide advance notice or the right to remove their children. In addition, the School Committee has decided that teachers must be able to teach topics they feel are appropriate without the requirement parents be notified in advance."
Why is it that gay/lesbians seem to have more rights than we do? And why, if we are all equal, are we not being protected in the same ways?
Because "rights" are now being created by the state, rather than coming from Nature. According to natural law, you cannot possibly possess a natural right to perform an unnatural act. Once Nature is removed as the moral authority, you can declare anything equal to anything else – because it is simply based upon will. If the act of sodomy is then declared to be equal to the marital act (which is what the Supreme Court has done), the new version of equality requires the teaching of it as morally normative. In other words, this equality argument can quickly be turned against you by saying equality requires the teaching of sodomy. In fact, that is the argument of the homosexual movement. In order to defeat it, we have to show that rights come from Nature, not the state, and that sodomy is unnatural.
Will we ever be able to recover from this disaster in our world?
Yes. Reality always wins in the end. Reality is on our side. Illusion always leads to disillusion. The question is what will be left by the time this happens. The answer to that question depends on us. We must put our souls in order and steadfastly refuse to comply with this profound lie about what human beings are and reassert the truths of the "Laws of Nature and of Nature's God." On the basis of reason alone, that is what I try to do in my book.


text:
How should I handle a nuisance tenant?
Landlords almost never have issues with their renters, but things can sometimes go wrong. Here's how to handle nuicance tenants
Most of the time, tenants pay the rent on time and keep your property in a reasonable state.
But what if the rent fails to arrive, or your tenant starts causing problems with the neighbours? What if they cause damage, or allow the property to become unreasonably dirty?
Getting stuck with a nuisance tenant can leave you in a difficult position. This guide explains how to handle the situation – whether you are dealing with non-payment of rent, unacceptable behaviour, or simply need to regain possession of your property for personal reasons.
Non-payment of rent
Non-payment of rent is one of the most common problems faced by landlords.
Making a formal, written demand after a few days have passed is a sensible first step.
In many cases, a quick call to the late-paying tenant is all that is needed. But if your tenant ignores your calls, or fails to pay despite promising to do so, it's time to take a different course of action.
You should ask for any outstanding amount to be paid straight away, at the same time reminding your tenant to pay the rent on time from now on.
If that fails, you can send further letters after, say, 14 and 21 days telling the tenant that you'll take legal action if the rent isn't forthcoming.
In cases where the tenant has a guarantor, it's also worth chasing the rent up this way at this time.
Then, once the next month's rent is due, making the tenant two months in arrears, you can take action to evict him or her and claim possession of your property under the Housing Act 1988 (see below for how to do this).
Remember - landlord insurance can prove a lifeline should you end up with a tenant who does not pay the rent. A standard policy will cover rent arrears for up to five months.
Bad behaviour
As a landlord, you may also have to deal with a tenant who behaves anti-socially or causes damage to your property.
According to the Residential Landlords Association, landlords are not generally responsible for private nuisances such as noise caused by their tenants – unless, at the time of the letting, the nuisance was inevitable or almost certain to occur.
In certain circumstances, however, you could be liable if you fail to take action to resolve the problem.
For any damage identified when tenants move out, meanwhile, you are entitled to deduct the amount required to rectify it from the deposit paid at the start of the tenancy.
If it is more than this amount, you may have to take legal action against the tenant to claim the necessary compensation.
For damage reported by the tenant during the rental period, the best solution is to come to an agreement about how any resulting costs will be paid.
Assured Shorthold Tenancy agreements should outline the obligations of both parties in such circumstances.
If you are worried about a prospective tenant, some insurers will carry out a full rental history check for a small charge.
Evicting a tenant
Need to get rid of a nuisance tenant? You can issue him or her with a notice under either Section 8 or Section 21 of the Housing Act 1988.
Section 8 notices can be served during an Assured Shorthold Tenancy lasting say six or 12 months.
Qualifying grounds for a notice of this kind include non-payment of rent, and breaking the terms of the tenancy, for example by illegally subletting the property.
In the case of rent arrears, at least two months' rent must be outstanding for a notice to be served.
Section 21 notices can be used to regain possession of a property at the end of an Assured Shorthold Tenancy or during a periodic tenancy.
No reason needs to be given, which is why landlords wishing to sell the property often resort to notices of this kind when tenants refuse to cooperate.
However, Section 21 notices can only be served to coincide with the end of the rental period (or the "break clause"), and the tenant must be given at least two months to move out.
If a tenant ignores either a Section 8 or Section 21 notice, you will then need to obtain a court order to evict him or her.
Landlord insurance often covers at least some of the costs incurred evicting a problem tenant.


text:
Region/Concept: North America, Movement
Sub-Concepts: Altar, Effusion, Outpouring, Containment
Description: Diana al-Hadid creates architectural sculpture titled "Suspended After Image."
This staircase (itself a cascade of falling cloth, paint, and forms) leads to some kind of altar. But what kind of sanctuary or shrine is produced through a visual criterion of gushing and effusion? Is there a typology of the sacred that generates itself through the forces of torrent and outpouring (that which spills infinitely, bleeds everywhere), and then another that manifests only through processes of containment and drought (that which wastes nothing, overflows nowhere)? Two separate portals to the otherworldly, stretched along an axis between excessive secretion and ascetic desiccation. In the former case, for which this sculpture constitutes a kind of hallowing (of the history of flagellation, running wounds, and gods meant to be drunk downward), we see a man's torso trickling across the planks in a way that links human destiny to a greater liquid metaphysics. And in the latter case, we are reminded of the fasting and self-deprivation of so many monks or saints (a history of parched throats, heavily cloaked bodies, and ethereal vows), or even the "thugees" of India whose worship of the goddess of destruction led them to treat murder as a sacred rite…though to be performed without the loss of a single drop of blood, and thus prone to committing acts of strangulation with silk scarves. One remembers the caravans upon which they preyed, and the structure of honor/violation through which any emanation or streaming of the veins was purely forbidden. Thus one wonders again whether different attributes of the miraculous are partitioned along this strange choice: whether to let flood or to bottle the world of wet and dripping things.
Jason Mohaghegh


text:
The Estonian selection Eesti Laul once again featured a number of great songs. This blogger enjoyed Tanja's winning song although I feel Estonia had stronger songs... here's a couple of my favourites:
Lenna Kuurmaa - Supernoova
Supernoova is a a lovely ballad, sung in Estonian! Lenna would've been a great choice. She has entered Eesti Laul on numerous occasions and even represented Switzerland in 2005 - with Vanilla Ninja. Would she have qualified? I don't know to be honest but it's a sweet song! A great effort from Lenna.
Sandra Nurmsalu - Kui tuuled pöörduvad
Sandra Nurmsalu's entry was absolutely the best song in the Estonian national final, in my opinion. Her song was unique, stunning, fabulous and very special. The jury ranked her 9th out of 10 participants and she came 3rd in the televote... What a shame!! Sandra represented Estonia in 2009 with her band, Urban Symphony, and achieved 6th place in the final!
Monday, 4 August 2014
Missed Opportunities 2014: Estonia!
1 comment:
- Anonymous4 August 2014 at 11:12
Nope, and nope. Both acts were - uninspiring in the finals. They got trashed by the judges and the public alike.ReplyDelete
The counterprogramming option was Super Hot Cosmos Blues Band, who as a traditional rock band with a catchy tune, would have stood out in the Eurovision crowd. They are tearing up the Estonian festival circuit this summer with their new tunes.
Subscribe to: Post Comments (Atom)


text:
Be Proud to be a real estate agent
In this inspirational video Dave Werner, a top-producing agent, broker-owner and trainer, reminds us that real estate agents should be proud of what they do, what they have achieved, and why they should feel confident about their commission.
Dave is the Broker Owner of Nextage Unlimited Real Estate. Throughout his prolific career Dave has won numerous sales and management awards and has served in many capacities, including recruiting, managing, and professional coaching. He has always converted his diverse background into extraordinary service and integrity for his clients and enjoys helping his agents succeed in their business through developing individual skills and strengths—and stretching one's vision to new levels.


text:
The Fuji X100S is a beautiful retro looking camera, with very high end features. I was attracted to it since it looked very much like my first 35mm camera that my dad had bought when he was in Japan in the service. The camera is a fixed lens 23mm f2.0 (very fast) and very sharp. They do sell converters for even wider angle, and lens hoods, etc. It does include a built-in flash which works extremely well. In fact, if you just left this camera on auto mode, it would work nearly effortlessly in any grabshot, family outing kind of thing. It is small, solid but not heavy. The quality is evident when you look at the seams, the metal finish, and well placed buttons.
What I liked most:
1. Cool. Just dang cool.
2. The Velvia simulation mode. Velvia reverse negative film makes gorgeous saturated slides that make landscapes look amazing. I tried the camera out on my first day, and here's what I came up with in the Velvia simulation mode:
3. EFV viewfinder; this thing is nifty since you can pop a lever on the front and it will give you the electronic viewfinder, representing the exposure level you are about to capture as well as focus points and all the other good information. If you are having trouble seeing (as in, your manual strobe will fire but until there there ain't much to focus on) you can use the eye sensored straight through the viewfinder. It shows you exposure info, and where your autofocus point is.
4. Rear display; this is a very high resolution display that can also be used as the third focus preview method. It is not touch screen, but your 41 autofocus points are easily accessible with the command wheel.
5. The 41 focus points! Seriously, this is good stuff for a compact camera of any kind, and really works good here.
6. Panorama mode: I didn't discover this feature until after my first day when I stitched vertical shots together to make the Newport Back Bay shot. It works exceptionally well, and behaves much like the iphone style pano apps.
7. High quality images, low light shooting. Very good high ISO shots. The APS-C sensor on this camera has some filtering removed so you are getting more sharpness than typical dslr implementations of this sensor size. Stick that baby in auto and see how good your impromptu shots turn out!
8. Multiple exposure mode: really cool, and something that Canon just came out with finally on their dslr's. Street scenes would be killer with this feature.
1. Wide shots; great for street scenes, great for landscapes. Not as good for portraits. The depth of field at the distance of 10 feet or so is quite large, even at f2.0. So if you are all about headshots with creamy background and the subject popping out, you will need to move in to about 4 feet...and that does not have the same "compressed distance" effect. Most people would not care about this though...
2. Could use a reticulating screen. Really, I do want to be able to do nice video with my photos, and having a waistlevel viewfinder or over the head monitor is pretty important to keep a steady shot and follow focus.
3. Does not autofocus video.
4. Expect to be able to review the shot on the back screen by just clicking the review button; however if you are shooting in evf or optical viewfinder, you are reviewing in the EFV or you will have to hit the display button after going to optical viewfinder. Not intuitive and even after about 50 shots I kept stumbling around to get to previews. Purists would say "hey, you are a photographer you should not even need this" but I have bad eyes and getting critical focus takes work for me....missing a shot because I didn't check is just silly.
All in all, this camera would make a great travel camera, and will inevitably make people go "whoah...looks like a film camera!" The film modes are wonderful, and if you could get by with a "normal" focal length (35mm equiv.) then this camera is top notch quality. If money were no object, I'd keep this simply because it is gorgeous, functional and feels good to hold.
January (3) February (3) (2) March (2) (2) April (2) (1) May (1) (3) June (3) (1) July (1) August (1) September (1) (8) October (8) November December
January February March (3) April (3) (2) May (2) June (1) July (1) (1) August (1) September October November December
January (1) February (1) March April May (2) June (2) July August September (1) October (1) (1) November (1) December
January February March April May June July August September October November (1) December (1)
(1) January (1) February March April May June July August September October November December
January February March April May June July August September October (1) November (1) December
January February March April May June July August September October November December
January February March April May June July August September October November December
January February March April May June July August September October November December
(1) January (1) February March (2) April (2) May June July (1) August (1) September October November December


text:
The Vegan vs. Omnivore Debate Part 3
Of Media, PeTA/HSUS, and Consumers Alike
If the media gets so much a whiff of something bad that happened in the animal agricultural industry, like BSE (Mad Cow Disease), slaughter-house horrors, or inhumane treatment of animals, they're on it like a flock of vultures on a dying cow. They really put out their best efforts to horrify people, and they do a fine job of it too. It doesn't help when they start stereotyping all livestock farmers as uncaring, profit-driven individuals. The reality is that are a few folks out there who raise livestock and shouldn't, and it is these few individuals that help shine a bad light on the animal agricultural industry itself.
Animal activists love to show us how these animals that are raised for meat have feelings too. They express that animals are sentient, feeling beings that "share the same emotions that we do as humans." While this is does has some merit to it, what they don't realize is that animals are not humans, even though humans are animals, in our own way. Animals have their own way of expressing their own "feelings," if you will, and live in the now, never in the past or future like what us humans do. Yes, animals are indeed capable of feeling pain, discomfort and displeasure, but as I mentioned before, they do it in their own way, not in a way that we humans do and at our level. They also want people to "understand" that because they "are sentient, feeling beings," they should be treated like they way we treat other people. What gets me is that don't they realize that all herbivorous animals, including wildlife, are there because they are a part of what is called the food chain? The animals we raise to eat are a part of this network, no matter if they have feelings like we do or not.
But, that said, we do not have to treat animals like those that are money-producing machines, like many are in factory farms: caring for and treating livestock like nature would is more humane than shutting them up in cages or stalls for all of their lives. So animal activists do have a point, and I do agree with them that animals that are shut up in tiny cages with little room to move around, turn around, carry out its natural behaviors and communicate with other animals of its species is simply not humane and not right. But going to the extreme of destroying animals because "it's for their own good" isn't right either. Everything deserves a life, and it's better to give it as best a life as possible instead of destroying it.
Consumers are the worst part of this whole veganism thing. Many consumers today are many generations removed from their farming ancestors, and they do not really care much about what they eat unless it tastes good or looks good. This makes them much more easier targets for animal rights groups to "empty their wallets" in a manner of speaking. Propaganda and advertisements about animals being abused, neglected, whatever PeTA and HSUS have in their arsenal are highly useful for these groups to get these consumers on their side, and even convince them to change their eating habits "for the better of the animals," or "for the better of the environment." They are also unaware of where their food comes from; most of it's not what they think or where they think.
Much of our food found in the major grocery store is imported from other countries or other parts of the country, though we know very little of where it actually came from, how it was grown, and how it got here. Cities have grown because of the increase of the human population: and the livestock and food industry had to grow and expand to accommodate that growth and increase in many different tastes, cultures and ethnicities. Corn is in almost everything we eat, right down to the chemicals derived from the corn kernels that are put into packaged cookies, potato chips, wafer bars,Twinkies, and many other packaged foods. Almost all of the beef sold in major grocery stores are corn or grain-fed. Almost all milk from dairy cows comes from cows that are grain-fed. Even pork and chicken. Most of the fruit and vegetables sold at these major grocers are grown on a mass-produced scale over 3000 miles away. The "grain" we eat from bread is from GMO (genetically modified organism) cereal grains that have been selected to increase the amount of seeds on the wheat or rye plants, so crop farmers get more bushels per acre every year. Corn is far more GM (genetically modified) than other cereal crops. MIchael Pollan, author of The Omnivore's Dilemma, describes more how King Corn has taken over what and how we eat, and is a book that has a few more eye-opening details in it.
Because many consumers are blind to where their milk, beef, chicken and pork come from, they do not realize how these animals are farmed, and are shocked to realize that much of the meat they eat come from factory farmed animals, and not from those out on pasture or free-range. Some get so shocked that they decide to go vegan. Suddenly switching your diet to "save the animals" is a bit extreme. If you don't want to support factory farming but don't want to give up on your omnivorous diet, buy locally raised meats, meats that come from family farms, not "factory" farms. But there are many out there that do not have the time or the money to switch their diets, and instead prefer to get the meat that they can see through the cellophane, rather than the "stuff" wrapped in brown paper.
The Politics of it All
I find that in the States, the government is the worst culprit. The government (or at least, in part, the UN) seems to be encouraging intensive livestock production, and I don't mean the intensive livestock production in terms of grazing on pastures. No, they're encouraging the very thing that many vegans are rampaging about: Factory Farming. These corporate farms are getting more money for their mass producing farms, and major feedlots are getting more credits for what and how they feed livestock. Studies have shown time and time again that grain-feeding of cattle is the worst possible thing you could do to these animals, in terms of health, mobility, and environmental concerns. Health problems are remarkably obvious when looking at both the animals that are fed grain and the humans that eat the meat from those grain-fed animals. Environmental concerns from feedlots are even more stark, despite the FAO's ability to state that intensification of livestock is better for the environment. Scientists have found, in opposition to FAO's statements in Livestock's Long Shadow , that there is far more problems with soil erosion, soil pollution, water pollution, and air pollution than those small family farms which raise their livestock naturally, i.e. on grass.
Major meat packing companies which control what kind of beef they want to run through their slaughter plants are also funded by the federal government. Much of these meat packers, like the two giants in Canada (XL Foods and Cargil), OWN feedlots. And these feedlots are not like the privately owned smaller ones like those found up in the Athabasca-Westlock-Barrhead counties of Alberta. These feedlots are HUGE, buying and feeding hundreds of thousands of cattle, and then processing them in their own slaughter plants. With only two meat packing companies controlling the prices and the kind of cattle they like to see be run through their plants, it's no wonder that many family farms with cow-calf herds are going out of business. And here in Canada we don't have the worry about Agri-Food Canada getting suckered in to the bull that the UN FAO has published in their book like the USDA has. The USA has at least 5 times as many major meat packing companies as we do in Canada, and more trading partners than they can shake a stick at. They don't know how good they have it.
The BSE episode in 2003 hasn't helped matters here either. Since then we've had to deal with less income coming from exporting less beef to less trading partners (32 out of 100 are in trade with Canada), and as a result, beef prices have constantly decreased. With lower beef prices, more farms and ranches are pulling out. Even the big meat packers are seeing a decrease in profits (even though they are making far more than the average beef producer). I find it quite ironic that the United States state that they are "BSE free" when the cow that caused the whole BSE mess in 2003 came from the States, as did the subsequent other 10 or more cases that popped up in Canada. Why, if the USA has slammed down the suggestion to enforce more stringent testing of reportable diseases like BSE, as well as efforts to increase traceability in livestock, are they saying they are BSE free? Isn't that called lying? This "BSE-free" horse-crap that they tell everyone who will listen reminds me of the EPA's efforts to promote veganism and push the false statements that livestock in America are bigger greenhouse gas producers and the least healthiest food products to consume than any other. That, in itself, is also a lie. But hey, the general population seems to be stupid enough to buy into all this, which makes it easy to gain support from the urban-majority and all vegans and vegetarians that are around.
The funny thing is, is that we tend to find out the truth when it's too late, just like what happened with the Great Dust Bowl in the 1930s when vast areas of land were overgrazed and tilled for crops, as well as the Severe Winter of 1886-87 when thousands of cattle starved and froze to death because of overgrazing and lack of winter feed. Perhaps the same will come about if the US government get their way. But in all honesty, lets hope that does NOT happen.


text:
If Renewal by Andersen of Long Island replacement windows could talk, they would have plenty to say.
For one thing, windows are a big part of everyday life on Long Island in the 21st century. Our neighbors watch their children playing outside while sitting in a chair near the over-sized picture window in the den. We listen to the birds singing through an open bedroom window as the sun lifts above the horizon. Some of us take advantage of natural light streaming through a window in the breakfast nook to read the morning paper. Modern replacement windows shape our lives in many ways from improving our health by blocking airborne dust and debris to making daily life safer.
Replacement Windows Block Unwanted Elements to Improve Health
Very few occupied homes in the United States today have such poorly performing home windows that owners have to seal their windows with damp sheets to keep dust out. That wasn't always the case. During the Dust Bowl on the Great Plains during the 1930s, people died from inhaling dust and debris indoors. As Pulitzer Prize-winning journalist Timothy Egan explains in his book The Worst Hard Time, moving from sod homes to modern – at least at the time – framed houses didn't ensure families they were safe from all of the elements, but there were improvements in many ways.
Let's face it, here on the Island we don't usually have to worry about extreme dust storms like they do out West. However, modern technology and manufacturing techniques have benefits for us, too. You have access to replacement windows that block air and moisture leaks so effectively very few homeowners will notice excessive dust accumulation indoors – even if you don't dust frequently. What a change! With TruScene insect screens constructed using an ultra-fine mesh fabric, you'll have an extra layer of protection from pollen and spores that find their way into our homes through open windows that can trigger seasonal allergies. And, with enhanced insulating properties you'll hear fewer noises from outside, which often means a better, more restorative sleep, yet, another health benefit.
Replacement Windows Bring in the Good Stuff
While blocking unwanted dust and contaminants is a good thing, you want to use your windows to bring in abundant sunshine to keep a home healthy. Natural light is so important to human health that regulatory agencies set building codes to make sure that happens. The International Residential Code (IRC 2012) recommends all single family homes have windows that enable sufficient light to enter each room. Their standards say that glass surfaces in egress windows should be at least 8% of the total square footage of the room, or rooms, served. That means that a 20 square foot x 20 square foot room would need a window or windows (400 square feet) will need at least 32 square feet of glass surface. You could install one large 8′ x 4′ window, but that is a pretty large operable window if you want an awning or hopper style. For very large rooms, you may choose to install large picture windows and smaller casement windows or sliding windows to allow ventilation – which have a recommended surface area of 4% according to the code. The point is to encourage sufficient airflow to keep our indoor air healthy and bring in plenty of abundant natural light to illuminate our spaces with less artificial light.
Replacement Windows Allow Entrance & Egress
Along with keeping our homes healthier and more secure every day, modern replacement windows provide safe entrance and egress during emergencies. Whether you install double-hung windows, sliding windows and patio doors or casement windows, you need to be sure they are large enough for emergency personnel to get inside if you need help getting out, or need medical attention and cannot open the door. Well-designed replacement windows won't stick or hang, as long as you periodically clean the tracks and check for damage to weather-stripping and other components that enable operation.
Renewal by Andersen of Long Island Will Help You Gather All the Information You Need to Update Your Home
While our replacement windows are pretty extraordinary, we will admit they cannot speak to their many advantages themselves. If you want more information about the wonders of modern technology and replacement window features, simply fill in the short form on this page, or give us a call at 1-877-313-9052 and speak to a professional replacement window and patio door consultant today.
Download our Free Guide to Long Island Replacement Windows
Learn Everything You Need to Know BEFORE Buying Replacement Windows
- The Difference Between Replacement and New Construction Windows!
- The Different Kinds of Frame Materials and What That Means to Your Windows' Performance and Longevity!
- How the Right Glass Can Save You Money on Your Heating & Cooling Bills!
- The Critical Role Proper Installation Plays in the Performance, Durability and Warranty of Your New Replacement Windows!
- What Features and Options are Important to You and What Role They Play in Your Ultimate Satisfaction Today, and for as Long As You Live in Your Home!


text:
Well the good news today is that the Loperamide did its stuff and I managed to complete the 105km to Jaipur.
Could have done without the headwind. It's also warming up, 35 degrees C today.
Now completely zonked but it's a rest day tomorrow.
Follow this link to see the route: Route to Jaipur


text:
Today's post is all about "How to Style with StyleWe".
StyleWe it's an online fashion shopping platform featuring independent fashion designers that covers many different styles and fashion news (shipping worldwide!).
I have created three quick outfit ideas for different kind of occasions. Going to the office, going shopping or visiting a gallery? Here are some inspirations for you.
HOW TO STYLE for the Office:
wearing designer's Philis
I would keep it a little monochrome with neat lines. The knitted cardigan gives it a little college look.
I would keep it a little monochrome with neat lines. The knitted cardigan gives it a little college look.
HOW TO STYLE for going Shopping:
I would stay casual and comfortable wearing this long grey dress and a checked skirt to match it with a little edgy touch (this long transparent black coat).
HOW TO STYLE for an Exhibition:
I love me some edgy items and this overall midi skirt says it all. I would wear it with this black long wool coat and a little artsy blouse to keep it casual but cool.
Visit StyleWe Youtube for more inspirations and website StyleWe for more designs.
Instagram: https://www.instagram.com/
Twitter: https://twitter.com/stylewe


text:
One of my submarine-related interjections between posts about the Civil War…
Tomorrow is the 111th birthday of the U.S. Submarine Force… but, today marks 48 years since the loss of all hands (129 total, including 17 civilian technicians), aboard the U.S.S. Thresher.
At 7:47 a.m., on April 10, 1963, in deep-diving tests off the coast of Massachusetts, the Thresher began to descend to test depth (approximately 1,000 feet). After a gradual descent, test depth was reached at 8:25. In just over a half hour, a rupture occurred in one of the pipes in the engine room. In response, the sub was ordered to the surface, but, in the course of blowing the main ballast tanks, moisture began freezing and blocked air flow. At about the same time, water leakage likely shorted circuitry, causing an automatic reactor shutdown, and thereby a loss of propulsion. Now in a descent, by 9:17 the last transmission was received from the Thresher, stating that she was exceeding test depth. Sometime thereafter, Thresher likely imploded.
She and all aboard rest 8,400 feet below the waves, 190 nautical miles east of Cape Cod, Massachusetts.
On April 11, 1963… the 63rd anniversary of the U.S. Submarine Force, the Navy officially announced the loss of the Thresher.
To those aboard… on eternal patrol….


text:
Released: 31 July 2007
Hot on the heals of the fabulous Royksopp Back To Mine mix, London's Bugz In The Attic rose to the challenge in 2007 and delivered nothing short of a summer sizzler.
On their own productions this nonchalant, occasionally chaotic octet of musicians have a natural knack for producing quality dance music, a trait that is ever present on this 19 track musical odyssey. In typical Back To Mine fashion this mix is a melting pot of musical styles fused together with great studio prowess.
Opening with the Maurice Fulton produced 'Lets Get Sick' this mix instantly pricks up the listeners ears before moving into some serious punk funk courtesy of 80's Rough Trade favourites Maximum Joy. The late great J Dilla covers just a smidgen of the hip hop on here before leading into Rammelzee's electro classic 'Beat Bop'. Jack Wilson adds some carnival flavour whilst Bodysnatch and Unique 3 inject some old skool rave before taking it all down a notch. The Sylvers and Kid Creole add a touch of vintage soul, The Fearless Four start the uprock for those partial to a windmill or two followed by the sugar sweet voices of Leon Ware and Carroll Thompson who lead into Earth, Wind & Fire's aptly titled climax 'The Departure'.


text:
For Well's Sake
on February 27, 2018 at 5:25 pm
Chapter: Coming to Terms
Characters: Depressed Dave, Hope the cat, Just Jane
Therapy isn't just about talking. Psychologists are trained to identify potential issues, provide frameworks to ease a client out of unwanted behaviours, or help patients and clients figure out issues that might not even appear on the radar. There's a ton of work that goes on behind that.
I'm grateful to my therapist for her patience and care in dealing with me. Without her, I don't think I could even have made the progress I've made so far.


text:
Warning over deadly fish parasite
SCOTLAND - Scotland's river managers are warning that one careless angler could wipe out the country's wild salmon stocks and ruin rural communities.
It is feared an angler could accidentally introduce the parasite
They fear that a fishermen will accidentally import a deadly parasite which has already devastated stocks in 20 Norwegian rivers.
The salmon farming industry said it would be shut down within 18 months of a widespread outbreak.
The Scottish Executive is seeking new powers to reduce the risk.
Source: BBC News


text:
500 Internal Server Error
Welcomt to Krist Photography, we are Photographers-Portrait serving Machesney Park area, IL. Visit us at 623 Poppy Dr, Machesney Park, IL, 61115-1559 viewed so far 2450 times. View Location Krist Photography. photographers portrait -- Tuesday, March 24, 2009 Krist Photography reviews
Location Address:
Krist Photography
623 Poppy Dr
Machesney Park,
Contact Krist Photography
Website: www.kristphoto.com
Email: ******@kristphoto.com
Categories: Photographers-Portrait [more businesses in Photographers-Portrait]
Website: www.kristphoto.com
Email: ******@kristphoto.com
Categories: Photographers-Portrait [more businesses in Photographers-Portrait]
Krist Photography Reviews
Khiee reviewed on Krist Photography
Disclaimers: 1. I do know Neil van Niekerk 2. I use very little flash I've known Mr. Niekerk for more than a few years and there are few orotpghaphers for whom I have as much respect, personally or professionally. While I am known for my available light work I do consider a mastery of light, be it available or supplemental, to be crucial for the production of great images. Mr. Williams states, eloquently, in his foreword that we live in the age of the quick-fix during which period it really does seem to be de rigueur to eschew knowledge and learning. If you recognize that flash is your weak point, or if you desire to improve your lighting skills and knowledge then I suggest that this book should not only be on your purchase list, at the top , but also that you do spend the time reading, practicing and understanding the techniques and concepts presented in it, paying particular attention to Mr. van Niekerk's statement regarding manual exposure; You decide. Not the camera. This is of key importance and is often overlooked or neglected The book itself is very well written, using precise, unambiguous language leaving little, if any, room for misunderstanding. The chapter subjects are comprehensive. The diagrams are clear and concise and each and every photograph in the book illustrates its point very clearly. My only issue with the foreword is that Mr. William's statement this is a fantastic book is that it is not in bold print! It is indeed a fantastic book. It's not a quick fix, I don't believe it was ever intended to be one. It does require reading and practice, after all practice does make perfect! George Weir posted on Sunday, March 04, 2012