Fetal hemodynamic response to aortic valvuloplasty and postnatal outcome: a European multicenter study.

OBJECTIVE: Fetal aortic stenosis may progress to hypoplastic left heart syndrome. Fetal valvuloplasty (FV) has been proposed to improve left heart hemodynamics and maintain biventricular (BV) circulation. The aim of this study was to assess FV efficacy by comparing survival and postnatal circulation between fetuses that underwent FV and those that did not. METHODS: This was a retrospective multicenter study of fetuses with aortic stenosis that underwent FV between 2005 and 2012, compared with contemporaneously enrolled natural history (NH) cases sharing similar characteristics at presentation but not undergoing FV. Main outcome measures were overall survival, BV-circulation survival and survival after birth. Secondary outcomes were hemodynamic change and left heart growth. A propensity score model was created including 54/67 FV and 60/147 NH fetuses. Analyses were performed using logistic, Cox or linear regression models with inverse probability of treatment weighting (IPTW) restricted to fetuses with a propensity score of 0.14-0.9, to create a final cohort for analysis of 42 FV and 29 NH cases. RESULTS: FV was technically successful in 59/67 fetuses at a median age of 26 (21-34) weeks. There were 7/72 (10%) procedure-related losses, and 22/53 (42%) FV babies were delivered at < 37 weeks. IPTW demonstrated improved survival of liveborn infants following FV (hazard ratio, 0.38; 95% CI, 0.23-0.64; P = 0.0001), after adjusting for circulation and postnatal surgical center. Similar proportions had BV circulation (36% for the FV cohort and 38% for the NH cohort) and survival was similar between final circulations. Successful FV cases showed improved hemodynamic response and less deterioration of left heart growth compared with NH cases (P ≤ 0.01). CONCLUSIONS: We report improvements in fetal hemodynamics and preservation of left heart growth following successful FV compared with NH. While the proportion of those achieving a BV circulation outcome was similar in both cohorts, FV survivors showed improved survival independent of final circulation to 10 years' follow-up. However, FV is associated with a 10% procedure-related loss and increased prematurity compared with the NH cohort, and therefore the risk-to-benefit ratio remains uncertain. We recommend a carefully designed trial incorporating appropriate and integrated fetal and postnatal management strategies to account for center-specific practices, so that the benefits achieved by fetal therapy vs surgical strategy can be demonstrated clearly. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Natural history of 107 cases of fetal aortic stenosis from a European multicenter retrospective study.

OBJECTIVES: Fetal aortic valvuloplasty (FV) aims to prevent fetal aortic valve stenosis progressing into hypoplastic left heart syndrome (HLHS), which results in postnatal univentricular (UV) circulation. Despite increasing numbers of FVs performed worldwide, the natural history of the disease in fetal life remains poorly defined. The primary aim of this study was to describe the natural history of fetal aortic stenosis, and a secondary aim was to test previously published criteria designed to identify cases of emerging HLHS with the potential for a biventricular (BV) outcome after FV. METHODS: From a European multicenter retrospective study of 214 fetuses with aortic stenosis (2005-2012), 107 fetuses in ongoing pregnancies that did not undergo FV were included in this study and their natural history was reported. We examined longitudinal changes in Z-scores of aortic and mitral valve and left ventricular dimensions and documented direction of flow across the foramen ovale and aortic arch, and mitral valve inflow pattern and any gestational changes. Data were used to identify fetuses satisfying the Boston criteria for emerging HLHS and estimate the proportion of these that would have been ideal FV candidates. We applied the threshold score whereby a score of 1 was assigned to fetuses for each Z-score meeting the following criteria: left ventricular length and width > 0; mitral valve diameter > -2; aortic valve diameter > -3.5; and pressure gradient across either the mitral or aortic valve > 20 mmHg. We compared the predicted circulation with known survival and final postnatal circulation (BV, UV or conversion from BV to UV). RESULTS: Among the 107 ongoing pregnancies there were eight spontaneous fetal deaths and 99 livebirths. Five were lost to follow-up, five had comfort care and four had mild aortic stenosis not requiring intervention. There was intention-to-treat in these 85 newborns but five died prior to surgery, before circulation could be determined, and thus 80 underwent postnatal procedures with 44 BV, 29 UV and seven BV-to-UV circulatory outcomes. Of newborns with intention-to-treat, 69/85 (81%) survived ≥ 30 days. Survival at median 6 years was superior in cases with BV circulation (P = 0.041). Those with a postnatal UV circulation showed a trend towards smaller aortic valve diameters at first scan than did the BV cohort (P = 0.076), but aortic valve growth velocities were similar in both cohorts to term. In contrast, the mitral valve diameter was significantly smaller at first scan in those with postnatal UV outcomes (P = 0.004) and its growth velocity (P = 0.008), in common with the left ventricular inlet length (P = 0.004) and width (P = 0.002), were reduced significantly by term in fetuses with UV compared with BV outcome. Fetal data, recorded before 30 completed gestational weeks, from 70 treated neonates were evaluated to identify emerging HLHS. Forty-four had moderate or severe left ventricular depression and 38 of these had retrograde flow in the aortic arch and two had left-to-right flow at atrial level and reversed a-waves in the pulmonary veins. Thus 40 neonates met the criteria for emerging HLHS and BV circulation was documented in 13 (33%). Of these 40 cases, 12 (30%) had a threshold score of 4 or 5, of which five (42%) had BV circulation without fetal intervention. CONCLUSIONS: The natural history in our cohort of fetuses with aortic stenosis and known outcomes shows that a substantial proportion of fetuses meeting the criteria for emerging HLHS, with or without favorable selection criteria for FV, had a sustained BV circulation without fetal intervention. This indicates that further work is needed to refine the selection criteria to offer appropriate therapy to fetuses with aortic stenosis. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Fetal aortic valvuloplasty: investigating institutional bias in surgical decision-making.

OBJECTIVES: Fetal aortic valvuloplasty may prevent the progression of aortic stenosis to hypoplastic left heart syndrome and allow biventricular rather than univentricular postnatal treatment. This study aimed to investigate whether blinded simulation of a multidisciplinary team approach aids interpretation of multicenter data to uncover institutional bias in postnatal decision-making following fetal cardiac intervention for aortic stenosis. METHODS: The study included 109 cases of prenatally diagnosed aortic stenosis from 13 European countries, of which 32 had undergone fetal cardiac intervention. The multidisciplinary team, blinded to fetal cardiac intervention, institutional location and postnatal treatment, retrospectively assigned a surgical pathway (biventricular or univentricular) based on a review of recorded postnatal imaging and clinical characteristics. The team's decisions were the numerical consensus of silent voting, with case review when a decision was split. Funnel plots showing concordance between the multidisciplinary team and the local team's surgical choice (first pathway) and with outcome (final pathway) were created. RESULTS: In 105 cases the multidisciplinary team reached a consensus decision regarding the surgical pathway, with no decision in four cases because the available imaging records were inadequate. Blinded multidisciplinary team consensus for the first pathway matched the decision of the surgical center in 93/105 (89%) cases, with no difference in agreement between those that had undergone successful fetal cardiac intervention (n = 32) and no (n = 74) or unsuccessful (n = 3) valvuloplasty (no fetal cardiac intervention) (κ = 0.73 (95% CI, 0.38-1.00) vs 0.74 (95% CI, 0.51-0.96)). However, funnel plots comparing multidisciplinary team individual decisions with those of the local teams displayed more discordance (meaning biventricular-univentricular conversion) for the final surgical pathway following fetal cardiac intervention than they did for cases without such intervention (36/74 vs 34/130; P = 0.002), and identified one outlying center. CONCLUSIONS: The use of a blinded multidisciplinary team to simulate decision-making and presentation of data in funnel plots may assist in the interpretation of data submitted to multicenter studies and permit the identification of outliers for further investigation. In the case of aortic stenosis, a high level of agreement was observed between the multidisciplinary team and the surgical centers, but one outlying center was identified.

Hypermobility among school children aged five to eight years: the Hospital del Mar Criteria gives higher prevalence for hypermobility than the Beighton score.

OBJECTIVES: The purpose was to investigate the distribution of hypermobility among school children aged five to eight years. METHODS: One hundred and twenty-eight participants were assessed using the Beighton score and the Hospital del Mar criteria. RESULTS: With the Beighton score using the cut-off ≥4, the prevalence was 12%, and with the Hospital del Mar criteria the prevalence was 34%. There were significantly higher scores for females on both the Beighton (p=0.01) and Hospital del Mar criteria (p<0.0001). The youngest children aged five to six years scored higher compared with the seven- and eight-year-olds (p=0.016). The knee flexion was most likely to be hypermobile (97%), followed by shoulder rotation (80%), thumb (31%), elbow (27%), metatarsal-phalangeal (16%), hip (15.5%), fingers (10%) or knee (10%), ankle (6%), trunk (4%) and patella (2%). CONCLUSIONS: Gender and probably age must be taken into account when children are assessed for hypermobility. The Hospital del Mar criteria need to be modified for some of the motions.

A population-based investigation of the autoantibody profile in mothers of children with atrioventricular block.

The objective of the study was to investigate the antigen specificity and occurrence of individual autoantibodies in mothers of children diagnosed with atrioventricular (AV) block in a nation-wide setting. Patients with AV block detected before 15 years of age were identified using national quality registries as well as a network of pediatric and adult cardiologists and rheumatologists at the six university hospitals in Sweden. Patients with gross heart malformations, surgically or infectiously induced blocks were excluded. Blood samples were obtained from the mothers and maternal autoantibody profile, including the occurrence of antibodies against Ro52, Ro60, La, SmB, SmD, RNP-70k, RNP-A, RNP-C, CENP-C, Scl-70, Jo-1, ribosomal RNP and histones was investigated in 193 mothers of children with AV block by immunoblotting and ELISA. Autoantibody reactivity was detected in 48% (93/193) of the mothers of children with AV block. In autoantibody-positive mothers, the vast majority, 95% (88/93), had antibodies against Ro52, while 63% (59/93) had autoantibodies to Ro60 and 58% (54/93) had autoantibodies to La. In addition, 13% (12/93) of the autoantibody-positive mothers had antibodies to other investigated antigens besides Ro52, Ro60 and La, and of these anti-histone antibodies were most commonly represented, detected in 8% (7/93) of the mothers. In conclusion, this Swedish population-based study confirms that maternal autoantibodies may associate with heart block in the child. Further, our data demonstrate a dominant role of Ro52 antibodies in association with AV block.

The serotonin transporter gene polymorphism (5-HTTLPR) and affective symptoms among women diagnosed with borderline personality disorder.

Gene variants of the serotonin transporter have been associated with vulnerability to affective disorders. In particular, the presence of one or two copies of the short (s) allele of the 5-HTTLPR polymorphism has been associated with reduced serotonin transporter expression and function, and vulnerability to affective disorders. To test for an association between variants of the serotonin transporter gene polymorphism (5-HTTLPR) and relevant clinical features of borderline personality disorder (BPD), a psychiatric disorder with symptoms characteristic for serotonin dysfunction, 77 women with BPD were genotyped in the 5-HTTLPR polymorphism. They rated their subjective experience of borderline-specific, depressive, anxious and obsessive-compulsive symptoms, and were interviewed about lifetime incidence of suicide attempts and self-harming acts. Carriers of two s alleles of the 5-HTTLPR reported more symptoms of borderline, depression, anxiety and obsessive-compulsive behaviours, but not of suicidal and self-injury behaviour, compared to carriers of a long (l) allele. This indicates that the 5-HTTLPR ss homozygous genotype might influence serotonin function affecting susceptibility to both borderline-specific, depressive, anxious and obsessive-compulsive symptoms in BPD, and leading to a more severe symptomatology related to these clinical features. Further, this suggests that 5-HTT gene variants may not be as influential on suicidal and self-injury behaviour in BPD.

Radiation doses in examination of lower third molars with computed tomography and conventional radiography.

OBJECTIVES: To measure organ doses and calculate effective doses for pre-operative radiographic examination of lower third molars with CT and conventional radiography (CR). METHODS: Measurements of organ doses were made on an anthropomorphic head phantom with lithium fluoride thermoluminescent dosemeters. The dosemeters were placed in regions corresponding to parotid and submandibular glands, mandibular bone, thyroid gland, skin, eye lenses and brain. The organ doses were used for the calculation of effective doses according to proposed International Commission on Radiological Protection 2005 guidelines. For the CT examination, a Siemens Somatom Plus 4 Volume Zoom was used and exposure factors were set to 120 kV and 100 mAs. For conventional radiographs, a Scanora unit was used and panoramic, posteroanterior, stereographic (scanogram) and conventional spiral tomographic views were exposed. RESULTS: The effective doses were 0.25 mSv, 0.060 mSv and 0.093 mSv for CT, CR without conventional tomography and CR with conventional spiral tomography, respectively. CONCLUSIONS: The effective dose is low when CT examination with exposure factors optimized for the examination of bone structures is performed. However, the dose is still about four times as high as for CR without tomography. CT should therefore not be a standard method for the examination of lower third molars. In cases where there is a close relationship between the tooth and the inferior alveolar nerve the advantages of true sectional imaging, such as CT, outweighs the higher effective dose and is recommended. Further reduction in the dose is feasible with further optimization of examination protocols and the development of newer techniques.

'If I don't smoke, I'm not a real man'--Indonesian teenage boys' views about smoking.

With a lack of tobacco control and regulation at the national level, Indonesia has been targeted by many national and transnational tobacco companies. The prevalence of youth smokers in Indonesia in 2005 was 38% among boys and 5.3% among girls. The aim of this study was to describe and analyse beliefs, norms and values about smoking among teenage boys in a rural setting in Java, Indonesia. Six focus group discussions with boys aged 13-17 years were conducted using a thematic discussion guide. Four themes were derived from the descriptive content analysis: (i) smoking as a culturally internalized habit, (ii) striving to become a man, (iii) the way we smoke is not dangerous and (iv) the struggle against dependency. Cultural resistance against women smoking in Indonesia remains strong. The use of tobacco in the construction of masculinity underlines the importance of gender-specific intervention. National tobacco control policy should emphasize a smoking-free society as the norm, especially among boys and men, and regulations regarding the banning of smoking should be enforced at all levels and areas of community. A comprehensive community intervention programme on smoking prevention and cessation should be a major focus of tobacco control policies in Indonesia.

Pre-operative radiographic evaluation of lower third molars with computed tomography.

OBJECTIVES: To report radiographic findings of examinations with computed tomography (CT) of impacted lower third molars with an intimate relation to the mandibular canal and to investigate how findings of a dark band across the roots of the lower third molar on panoramic views correspond to the CT findings. METHODS: CT images of 90 lower third molars (64 patients, mean age 34.6 years) in which plain radiography was insufficient to allow determination of the precise anatomical relations were reviewed retrospectively. Panoramic views of 88 teeth existed; these images were interpreted independent of the CT examinations with respect to presence of a dark band across the roots. RESULTS: In 31% of the CT images, the course of the mandibular canal was buccal, in 33% lingual, in 26% inferior, and in 10% inter-radicular. The tooth was in contact with the mandibular canal in 94% and with the lingual cortex in 86%. In 23%, grooving of the root by the canal was judged to be present. In 63% of the cases where a dark band across the roots was observed on panoramic radiographs, CT revealed grooving of the root. CONCLUSIONS: Pre-operative CT of lower third molars is motivated in selected cases when plain radiography is inconclusive. The finding of a dark band across the roots on panoramic radiographs is an indicator of grooving of the tooth by the canal and justifies a pre-operative CT examination. The absence of dark bands on panoramic views does not exclude grooving of the roots.

School achievements and schizophrenia: a case-control study.

OBJECTIVE: To compare school performance during middle childhood and adolescence among subjects later diagnosed with schizophrenia and their peers. METHOD: School records were ascertained from archives in 76 acutely symptomatic schizophrenic patients and 146 controls matched for gender and graded by the same teachers. RESULTS: At age 9, no differences in yearly graded school subjects were found. At 12, cases had higher marks in drawing/art and a tendency to excel in language and religion. At 15, the proficient performance in drawing/art remained, but cases performed worse than controls in gymnastics. The cases reported high frequency of school adaptation problems. Severity of psychotic symptoms at admission was associated with lower and declining marks. CONCLUSION: Schizophrenic patients seem to perform as well as their classmates in most subjects taught in compulsory basic school. Findings indicating specific talents in artistic ability and impairments in motor development need to be further investigated.

Nonconscious fear conditioning, visceral perception, and the development of gut feelings.

When people are presented with backward-masked images of fear-relevant stimuli and only some of these images are paired consistently with electric shocks, they can predict the occurrence of shocks even though they do not consciously know which images they have seen. We postulated that they may use the perception of visceral cues from the conditional fear response to facilitate the prediction of shocks. In this study, ability to detect heartbeats was used to index sensitivity to visceral cues. The results showed that subjects who could detect their heartbeats performed better than chance in predicting whether or not they would receive a shock during the conditioning task. The findings support the notion that hunches, or "gut feelings," are based in part on the perception of visceral cues.

Emotion drives attention: detecting the snake in the grass.

Participants searched for discrepant fear-relevant pictures (snakes or spiders) in grid-pattern arrays of fear-irrelevant pictures belonging to the same category (flowers or mushrooms) and vice versa. Fear-relevant pictures were found more quickly than fear-irrelevant ones. Fear-relevant, but not fear-irrelevant, search was unaffected by the location of the target in the display and by the number of distractors, which suggests parallel search for fear-relevant targets and serial search for fear-irrelevant targets. Participants specifically fearful of snakes but not spiders (or vice versa) showed facilitated search for the feared objects but did not differ from controls in search for nonfeared fear-relevant or fear-irrelevant, targets. Thus, evolutionary relevant threatening stimuli were effective in capturing attention, and this effect was further facilitated if the stimulus was emotionally provocative.

Fears, phobias, and preparedness: toward an evolved module of fear and fear learning.

An evolved module for fear elicitation and fear learning with 4 characteristics is proposed. (a) The fear module is preferentially activated in aversive contexts by stimuli that are fear relevant in an evolutionary perspective. (b) Its activation to such stimuli is automatic. (c) It is relatively impenetrable to cognitive control. (d) It originates in a dedicated neural circuitry, centered on the amygdala. Evidence supporting these propositions is reviewed from conditioning studies, both in humans and in monkeys; illusory correlation studies; studies using unreportable stimuli; and studies from animal neuroscience. The fear module is assumed to mediate an emotional level of fear learning that is relatively independent and dissociable from cognitive learning of stimulus relationships.

The face in the crowd revisited: a threat advantage with schematic stimuli.

Schematic threatening, friendly, and neutral faces were used to test the hypothesis that humans preferentially orient their attention toward threat. Using a visual search paradigm, participants searched for discrepant faces in matrices of otherwise identical faces. Across 5 experiments, results consistently showed faster and more accurate detection of threatening than friendly targets. The threat advantage was obvious regardless of whether the conditions favored parallel or serial search (i.e., involved neutral or emotional distractors), and it was valid for inverted faces. Threatening angry faces were more quickly and accurately detected than were other negative faces (sad or "scheming"), which suggests that the threat advantage can be attributed to threat rather than to the negative valence or the uniqueness of the target display.

Measuring the negative mood component of stress experiences: description and psychometric properties of a short adjective check-list of stress responses.

Negative Mood (NM) is a 19-items adjective check-list developed to assess negative mood and stress responses. The items of the scale reflect dimensions such as depressed mood, anxiety, anger and time urgency. The data were collected from four different samples, two random population samples and two smaller selective samples. The psychometric properties of the NM showed high internal consistency (Cronbach's Alpha). When analysed with principal components analysis, three factors emerged, anxiety/depression, time pressure, and anger. The factors emerged in all four samples, within samples and between gender. The NM factors were tested for convergent and discriminative validity by correlating them with other more established measures of different aspects of negative mood. The results showed high convergent and discriminative validity for two of the NM factors, i.e., anxiety/depression, and anger, whereas the results for the third factor, time pressure, were more ambiguous. This scale has proven to be useful in capturing some vital dimensions of negative affect across different kinds of populations.

[Inventory of geriatric psychiatry in Sweden. In short supply where demand does not determine resource allocation]. / Aldrepsykiatrin inventerad i Sverige. En bristvara där efterfrågan inte styr resurstilldelningen.

In 1999 The Swedish Society for Old Age Psychiatry conducted an investigation in all Swedish counties in order to survey existing organizations and resources for medical services intended for elderly people with psychiatric complaints. In some counties there were no out-patient units specifically aimed at elderly people with psychiatric diseases, while more than half had no out-patient units for the large group of elderly with psychiatric ailments other than dementia. The total number of beds was far less than international recommendations. Less than 5 per cent of the total number of Swedish psychiatrists and geriatricians hold positions exclusively for geriatric psychiatry. Access to geriatric psychiatry resources appears to be unevenly distributed, and may be found mainly in or near university cities.

Fear and anxiety: animal models and human cognitive psychophysiology.

The aim of this paper is to explicate what is special about emotional information processing, emphasizing the neural foundations that underlie the experience and expression of fear. A functional, anatomical model of defense behavior in animals is presented and applications are described in cognitive and physiological studies of human affect. It is proposed that unpleasant emotions depend on the activation of an evolutionarily primitive subcortical circuit, including the amygdala and the neural structures to which it projects. This motivational system mediates specific autonomic (e.g., heart rate change) and somatic reflexes (e.g., startle change) that originally promoted survival in dangerous conditions. These same response patterns are illustrated in humans, as they process objective, memorial, and media stimuli. Furthermore, it is shown how variations in the neural circuit and its outputs may separately characterize cue-specific fear (as in specific phobia) and more generalized anxiety. Finally, again emphasizing links between the animal and human data, we focus on special, attentional features of emotional processing: The automaticity of fear reactions, hyper-reactivity to minimal threat-cues, and evidence that the physiological responses in fear may be independent of slower, language-based appraisal processes.

Two-year results of a controlled study of residential rehabilitation for patients treated with percutaneous transluminal coronary angioplasty. A randomized study of a multifactorial programme.

AIMS: In a multifactorial lifestyle behaviour programme, of 2 years duration, to study the maintenance of achieved behaviour and risk factor-related changes. METHODS AND RESULTS: Out of a consecutive population of 151 patients treated with percutaneous transluminal angioplasty under 65 years of age, 87 were randomly allocated to an intervention group (n=46) or to a control group (n=41). The programme started with a 4 week residential stay, which was focused on health education and the achievement of behaviour change. During the first year of follow-up, a maintenance programme included regular contacts with a nurse, while no further rehabilitative efforts were offered during the second year. One patient died (control). During the second year the proportion of hospitalized patients was lower in the intervention group (4% vs 20%;P<0.05). Patients in the intervention group improved several lifestyle dependent behaviours: diet (index at 0, 12 and 24 months): 10.5+/-3. 4, 12.9+/-2.5 and 12.4+/-2.6 in the intervention group (I) vs 10. 1+/-3.2, 10.7+/-3.0 and 11.8+/-3.2 in the control group (C);P<0.05, exercise sessions per week: 2.5+/-2.3, 4.5+/-1.9 and 4.4+/-2.1 (I) vs 3.1+/-2.2, 3.5+/-2.3 and 3.7+/-2.7 (C);P<0.05, and smoking; 18%, 6% and 9% (I) vs 12%, 21% and 18% (C);P<0.05. This corresponded to improvement in exercise capacity (0, 12 and 24 months): 156+/-42, 174+/-49 and 165+/-47 W (I) vs 164+/-40, 163+/-49 and 156+/-48 watts (C);P<0.05. There were no significant differences between the two groups with regard to serum cholesterol levels at 0 and 24 months: 5. 4+/-0.8 and 5.2+/-0.9 mmol. l(-1)(I) vs 5.4+/-1.0 and 4.9+/-0.9 mmol. l(-1)(C); ns, low density lipoprotein cholesterol level: 3.6+/-0.8 and 3.4+/-0.8 mmol. l(-1)(I) vs 3.7+/-0.9 and 3.3+/-0.7 mmol. l(-1)(C); ns, triglyceride level: 2.2+/-1.6 and 1.8+/-1.3 mmol. l(-1)(I) vs 2.2+/-1.4 and 1.6+/-0.6 mmol. l(-1)(C); ns, body mass index (0, 12 and 24 months): 27.5+/-4.5, 27.0+/-4.3 and 27.4+/- 4.5 kg. m(-2)(I) vs 26.8+/-2.8, 26.9+/-2.7 and 26.9+/- 3.2 kg. m(-2)(C); ns, waist/hip ratio or blood pressure. The two groups did not differ in quality of life, or psychological factors. Return to work after 12 and 24 months was 74% and 78% (I) vs 68% and 61% (C); ns. CONCLUSION: This rehabilitation programme influenced important lifestyle behaviour and reduced some, but not all, important risk factors