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OBJECTIVES/GOALS: To develop feasible screening methods for activity of the enzyme Glucose-6-phosphate dehydrogenase (G6PD) with point of care applicability. METHODS/STUDY POPULATION: Current knowledge establishes the relevance of G6PD as a critical therapeutic determinant for effective antimalarial therapy due to the occurrence of mutations that lead to post-treatment severe adverse effects. We present our findings on development of cost effective point-of-care screening methodologies to ascertain G6PD deficiency. RESULTS/ANTICIPATED RESULTS: Using Patient Cohort Explorer and data from the Department of Pathology, we established the prevalence of G6PD deficiency at the University of Mississippi Medical Center, Jackson, MS as high as 11.8% (African-American males in all population, n = 2518). Next, for selection of potential target groups, we set up a protocol for recruitment of volunteers based on ethnic background, parental ethnicity, and medical history. G6PD activity was evaluated using point of care methods [Trinity Biotech test or CareSTART Biosensor], and Gold Standard quantitative spectrophotometric assay (LabCorp). Determinations in >20 subjects have showed comparable concordance. If used with a conservative interpretation of the signal, the Trinity Biotech test showed superior potential for use in the field relative to the CareSTART Biosensor. DISCUSSION/SIGNIFICANCE OF IMPACT: We established the prevalence of G6PD deficiency in our medical center. We have also setup tests for point-of-care assessment of G6PD. Pending evaluation of the relative tests performance, we will be in position to screen individuals and select them for a prospective clinical trial to evaluate the safety of antimalarial agents on scope of G6PD deficiency.
There are two major forms of long-term depression (LTD) of synaptic transmission in the central nervous system, which require activation of either N-methyl-D-aspartate receptors (NMDARs) or metabotropic glutamate receptors (mGluRs). In synapses in the perirhinal cortex we have directly compared the Ca2+ signalling mechanisms involved in NMDAR-LTD and mGluR-LTD. Whilst both forms of LTD involve Ca2+ release from intracellular stores the Ca2+ sensors involved are different; NMDAR-LTD involves calmodulin, whilst mGluR-LTD involves the neuronal Ca2+ sensor (NCS) protein NCS-1. In addition, there is a specific requirement for IP3 and PKC as well as protein interacting with C-kinase (PICK-1) in mGluR-LTD. NCS-1 binds directly to PICK1, via its BAR domain, in a Ca2+-dependent manner. Furthermore, the NCS-1-PICK1 association is stimulated by activation of mGluRs, but not NMDARs, and introduction of a PICK1 BAR domain fusion protein specifically blocks mGluR-LTD. Thus, NCS-1 is a component of a novel mechanism involved in mGluR-LTD.
There have been many changes in the treatment of bipolar disorder.
It is necessary to develop guidelines that can more aptly respond to cultural issues and specifics in different countries.
The Korean Medication Algorithm for Bipolar Disorder (KMAP-BP) was firstly published in 2002, with updates in 2006 and 2010. This third update reviewed the experts' consensus of opinion on the pharmacological treatments of bipolar disorder.
The newly revised questionnaire composed of 55 key questions about clinical situations including 223 sub-items was sent to the experts.
Combination of mood stabilizer (MS) and atypical antipsychotic (AAP) was the first-line treatment option in acute mania. For the management of severe psychotic bipolar depression, combination of MS and AAP, combination of AAP and LTG, combination of MS, AAP and AD or LTG, combination of AAP and AD, and combination of AAP, AD and LTG was the first-line treatments. Combination of MS and AAP was the treatment of choice for management of mixed features. Combination of MS and AAP, MS or AAP monotherapy was the first-line options for management of maintenance phase after manic episode. For maintenance treatment after bipolar I depression, combination of MS and AAP, combination of MS and LTG, combination of AAP and LTG, MS or LTG monotherapy, and combination of MS, AAP and LTG were the first-line options.
Despite the limitations of expert consensus guideline, KMAP-BP 2014 may reflect the current patterns of clinical practice and recent researches.
: Human impulsivity is a complex multidimensional construct encompassing cognitive, emotional, and behavioral aspects. Previous animal studies have suggested that striatal dopamine receptors play a critical role in impulsivity. in this study, we investigated the relationship between self-reported cognitive impulsiveness and dopamine D2/3 receptor availability in striatal subdivisions in healthy subjects using high-resolution positron emission tomography (PET) with [11C]raclopride.
Twenty-one participants completed 3-Tesla magnetic resonance imaging and high-resolution PET scans with [11C]raclopride. The trait of impulsiveness was measured using the Barratt Impulsiveness Scale (BIS-11). Partial correlation analysis was performed between BIS-11 scores and D2/3 receptor availability in striatal subregions, controlling for the confounding effects of temperament characteristics that are conceptually or empirically related to dopamine, which were measured by the Temperament and Character Inventory.
The analysis revealed that the non-planning (p = 0.004) and attentional (p = 0.007) impulsiveness subscale scores on the BIS-11 had significant positive correlations with D2/3 receptor availability in the pre-commissural dorsal caudate. There was a tendency toward positive correlation between non-planning impulsiveness score and D2/3 receptor availability in the post-commissural caudate.
These results suggest that cognitive subtrait of impulsivity is associated with D2/3 receptor availability in the associative striatum that plays a critical role in cognitive processes involving attention to detail, judgment of alternative outcomes, and inhibitory control.
The aim of this study was to monitor changes of prescription trends for bipolar disorder in inpatient settings in one university hospital.
A retrospective chart review was performed and data of 188 cases (2009–2012) and 118 cases (1998–2001) with a diagnosis of bipolar disorder were collected. Data on demographic variables, duration of hospitalization, kinds of psychotropic medications and the patterns of prescription over each four-year period were analyzed.
The proportion of patients with manic episode was decreased, whereas those of mixed and depressive episodes were increased. The use of lithium was decreased with the increased use of valproate. Increased use of lamotrigine in depressive episode was prominent. The use of combination treatment with mood stabilizers and antipsychotics was almost same level in both periods. The use of typical antipsychotics was significantly decreased and that of atypical antipsychotics was increased. Especially, the use of quetiapine showed great increase. In bipolar depression, the use of antidepressant was increased.
Data showed that quetiapine monotherapy had favorable effect on acute manic symptoms and well tolerated. Also this result suggests that quetiapine monotherapy may improve the self-perceived quality of sleep without any daytime impairment following sleep in acute manic patients.
Despite the advance in pharmacotherapy for posttraumatic stress disorder (PTSD), poor treatment adherence to pharmacotherapy for PTSD is a critical issue.
We intended to evaluate the predictors of premature discontinuation of psychiatric outpatient treatment after discharge for noncombat-related PTSD.
This study aimed to examine the sociodemographic and disease-related variables associated with the premature discontinuation of psychiatric outpatient treatment after discharge among patients with non-combat-related posttraumatic stress disorder.
We retrospectively reviewed the medical records of patients who were discharged with a diagnosis of posttraumatic stress disorder.
Fifty-five percent of subjects prematurely discontinued outpatient treatment within 6 months of discharge. Comparing sociodemographic variables between the 6-month non-follow-up group and 6-month follow-up group, there were no variables that differed between the two groups. However, comparing disease-related variables, the 6-month follow-up group showed a longer hospitalization duration and higher Global Assessment of Function score at discharge. The logistic regression analysis showed that a shorter duration of hospitalization predicted premature discontinuation of outpatient treatment within 6 months of discharge.
The duration of psychiatric hospitalization for posttraumatic stress disorder appeared to influence the premature discontinuation of outpatient treatment after discharge.
This study examined the prescribing patterns for medications to treat bipolar disorder in outpatient-based psychiatric practice focusing on atypical antipsychotics.
Retrospective chart review of patients admitted to a university hospital with a primary diagnosis of bipolar disorder in a period from January 2008 to December 2012 was conducted. We reviewed Diagnostic and Statistical Manual of Mental Disorders, fourth edition diagnosis and detailed clinical information at index episode. Psychotropic medications were grouped into six categories; atypical antipsychotics, typical antipsychotics, lithium, anticonvulsants, antidepressants, and minor tranquilizers. Severity, rapid cycling type, psychiatric comorbidity and disease duration were computed focusing on atypical antipsychotics.
In 344 patients who were prescribed major psychotropic medications, atypical antipsychotics were prescribed in 70.9% of subjects, anticonvulsants in 73.3%, lithium in 36.9%, antidepressants in 41.9%, and typical antipsychotics in 0.9% of subjects. About 12.5% of subjects were treated with the monotherapy. Atypical antipsychotics prescription was favored in subjects with manic and mixed episodes or severe episode. Prescribing trend is independent of rapid cycling type. Prescription of antidepressants were more frequent in subjects who were recently diagnosed as bipolar disorder or prescribed new medications or existed psychiatric comorbidity.
The development of bipolar disorder's psychopharmacology has been reflected in the prescription pattern of psychotropic medications in Korea. This study suggests that atypical antipsychotics have played major role in treatment of bipolar disorder.
We evaluated the difference in sleep skills between patients with and without need of hypnotics after sleep CBT.
Total 131 insomnia patients' sleep disturbances were assessed by visual analogue scales. Patients received 9 sessions of sleep CBT and were prescribed hypnotics for prn during 3 months. Sleep CBT was focused on the sleep hygiene and sleep stimulus-control guidelines. Sleep hygiene guidelines were Limit the time spent in bed (SH1), Get regular exercise (SH2), Avoid light at night (SH3), Avoid heavy meals or drinking (SH4), Quiet, dark, and comfortable bedroom (SH5), Avoid caffeine, alcohol, and nicotine (SH6), Relaxing bedtime routine (SH7),Llight bedtime snack (SH8), Remove the bedroom clock (SH9). Sleep stimulus-control guidelines were Go to bed only when sleepy (SSC1), Use the bed for sleeping or sex (SSC2), Get out of bed when unable to sleep (SSC3), Get up at the same time (SSC4), Avoid napping (SSC5). Each sleep skill state was evaluated by Likert scale, and they were compared between before and after CBT. Patients were divided into two groups: still need of hypnotics and no need of hypnotics after 3 months.
Forty-six (35.1%) patients replied they needed not hypnotics any more, but 85 (64.9%) patients replied they still needed hypnotics after CBT. Sleep VAS (25.26±8.52 vs. 32.64±8.95, p<0.001), SH2 (3.67±0.92 vs. 2.76±1.06, p=0.030), SH7 (4.08±0.55 vs. 2.76±0.76, p<0.001) were different in two groups.
Among several CBT skills, regular moderate exercise in daytime and a relaxing bedtime routine seem to be key components.
The Internet is commonly used in modern society; however, Internet use may become a problematic behaviour. There is an increasing need for research on problematic Internet use (PIU) and its’ associated risk factors.
This study aims to explore the prevalence and health correlates of problematic Internet use among South Korean adults.
We recruited the participants aged between 18 and 84 years old among the online panel of an online research service. The sample size of the survey was 500. Of these 500 participants, 51.4% (n = 257) were men and 48.6% (n = 243) were women. A participant was classified as a problematic Internet use (PIU) if his/her total score of Young's Internet Addiction Scale (YIA) was above 50. Stress Response Index (SRI), Fagerstrom test for nicotine dependence, lifetime average caffeine consumption, and sociodemographic query form were used in the collection of data. The t test and chi-square test were used for data analysis.
One hundred ninety-seven (39.4%) of the participants was classified into the PIU group. There was no difference of gender and education between PIU and normal users. However, PIU group was younger (mean 39.5 years) than normal users (mean 45.8 years). PIU group was more likely to have high levels of perceived stress, nicotine dependence, and drink more often caffeinated beverages (P < 0.05).
These data indicate that problematic Internet use is associated with perceived stress level, nicotine and caffeine use in South Korean Internet users. More research is needed to better understand the relationship between Internet use and mental health issues.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Studies suggest that alcohol consumption and alcohol use disorders have distinct genetic backgrounds.
We examined whether polygenic risk scores (PRS) for consumption and problem subscales of the Alcohol Use Disorders Identification Test (AUDIT-C, AUDIT-P) in the UK Biobank (UKB; N = 121 630) correlate with alcohol outcomes in four independent samples: an ascertained cohort, the Collaborative Study on the Genetics of Alcoholism (COGA; N = 6850), and population-based cohorts: Avon Longitudinal Study of Parents and Children (ALSPAC; N = 5911), Generation Scotland (GS; N = 17 461), and an independent subset of UKB (N = 245 947). Regression models and survival analyses tested whether the PRS were associated with the alcohol-related outcomes.
In COGA, AUDIT-P PRS was associated with alcohol dependence, AUD symptom count, maximum drinks (R2 = 0.47–0.68%, p = 2.0 × 10−8–1.0 × 10−10), and increased likelihood of onset of alcohol dependence (hazard ratio = 1.15, p = 4.7 × 10−8); AUDIT-C PRS was not an independent predictor of any phenotype. In ALSPAC, the AUDIT-C PRS was associated with alcohol dependence (R2 = 0.96%, p = 4.8 × 10−6). In GS, AUDIT-C PRS was a better predictor of weekly alcohol use (R2 = 0.27%, p = 5.5 × 10−11), while AUDIT-P PRS was more associated with problem drinking (R2 = 0.40%, p = 9.0 × 10−7). Lastly, AUDIT-P PRS was associated with ICD-based alcohol-related disorders in the UKB subset (R2 = 0.18%, p < 2.0 × 10−16).
AUDIT-P PRS was associated with a range of alcohol-related phenotypes across population-based and ascertained cohorts, while AUDIT-C PRS showed less utility in the ascertained cohort. We show that AUDIT-P is genetically correlated with both use and misuse and demonstrate the influence of ascertainment schemes on PRS analyses.
To investigate the association between parity and the risk of incident dementia in women.
We pooled baseline and follow-up data for community-dwelling women aged 60 or older from six population-based, prospective cohort studies from four European and two Asian countries. We investigated the association between parity and incident dementia using Cox proportional hazards regression models adjusted for age, educational level, hypertension, diabetes mellitus and cohort, with additional analysis by dementia subtype (Alzheimer dementia (AD) and non-Alzheimer dementia (NAD)).
Of 9756 women dementia-free at baseline, 7010 completed one or more follow-up assessments. The mean follow-up duration was 5.4 ± 3.1 years and dementia developed in 550 participants. The number of parities was associated with the risk of incident dementia (hazard ratio (HR) = 1.07, 95% confidence interval (CI) = 1.02–1.13). Grand multiparity (five or more parities) increased the risk of dementia by 30% compared to 1–4 parities (HR = 1.30, 95% CI = 1.02–1.67). The risk of NAD increased by 12% for every parity (HR = 1.12, 95% CI = 1.02–1.23) and by 60% for grand multiparity (HR = 1.60, 95% CI = 1.00–2.55), but the risk of AD was not significantly associated with parity.
Grand multiparity is a significant risk factor for dementia in women. This may have particularly important implications for women in low and middle-income countries where the fertility rate and prevalence of grand multiparity are high.
The Young Adolescent Project (YAP) is an ongoing longitudinal study investigating the effects of abuse and neglect on adolescent development. It is a multidisciplinary study guided by a developmental, ecological perspective, and designed to consider the physical, social, and psychological effects of childhood maltreatment through the transition from childhood to adolescence. Four waves of data collection have been completed, ranging from early (Mean age = 10.95) to late adolescence (Mean age = 18.24). Members of the maltreated group (n = 303) were selected from new cases that had been opened by the Department of Child and Family Services, whereas the comparison group (n = 151) were not involved with child welfare but lived in the same neighborhoods as the maltreated group. The study assessed a wide variety of domains including physical development (e.g., height, weight, body mass, pubertal development); physiological reactivity (e.g., cortisol); cognitive abilities; mental health (e.g., symptoms of depression, anxiety, trauma, and aggression); risk behavior (e.g., sexual activity, delinquency, or substance use); social development (e.g., self-esteem, competence, and social support); family environment; and exposure to community violence. Overall, our findings demonstrated the pervasive and persistent adverse effects of child maltreatment both within and across domains, but they also identified maltreated youth with positive functioning. Our hope is that this work will help move us toward identifying targets for intervention to cultivate resilience and positive adaptation after early maltreatment experiences.
To analyse how the auditory brainstem response changes in patients with sudden sensorineural hearing loss.
Data were collected via retrospective medical chart review.
Forty-three patients were included in this study. The mean latency of auditory brainstem response wave 1 was significantly longer for the affected side than for the unaffected side (p = 0.003). The mean latency of auditory brainstem response wave 1 was significantly shorter, and the mean amplitude of auditory brainstem response wave 1 was significantly larger, in the good response group compared to the poor response group. In forward conditional logistic regression analysis, auditory brainstem response wave 1 latency was an independent predictor of a good response (odds ratio = 34.37, 95 per cent confidence interval = 1.56–757.15, p = 0.025).
In patients with sudden sensorineural hearing loss, the latency of wave 1 of the auditory brainstem response was significantly increased and was related to prognosis.
Abnormal Ca homeostasis has been associated with impaired glucose metabolism. However, the epidemiological evidence is controversial. We aimed to assess the association between circulating Ca levels and the risk of type 2 diabetes mellitus (T2DM) or abnormal glucose homeostasis through conducting a systematic review and meta-analysis. Eligible studies were identified by searching electronic database (PubMed, Embase and Google Scholar) and related references with de novo results from primary studies up to December 2018. A random-effects meta-analysis was performed to estimate the weighted relative risks (RR) and 95 % CI for the associations. The search yielded twenty eligible publications with eight cohort studies identified for the meta-analysis, which included a total of 89 165 participants. Comparing the highest with the lowest category of albumin-adjusted serum Ca, the pooled RR was 1·14 (95 % CI 1·05, 1·24) for T2DM (n 51 489). Similarly, serum total Ca was associated with incident T2DM (RR 1·25; 95 % CI 1·10, 1·42) (n 64 502). Additionally, the adjusted RR for 1 mg/dl increments in albumin-adjusted serum Ca or serum total Ca levels was 1·16 (95 % CI 1·07, 1·27) and 1·19 (95 % CI 1·11, 1·28), respectively. The observed associations remained with the inclusion of a cohort study with ionised Ca as the exposure. However, data pooled from neither case–control (n 4) nor cross-sectional (n 8) studies manifested a significant correlation between circulating Ca and glucose homeostasis. In conclusion, accumulated data from the cohort studies suggest that higher circulating Ca levels are associated with an augmented risk of T2DM.
To define optimal thromboprophylaxis strategy after stent implantation in superior or total cavopulmonary connections.
Stent thrombosis is a rare complication of intravascular stenting, with a perceived higher risk in single-ventricle patients.
All patients who underwent stent implantation within superior or total cavopulmonary connections (caval vein, innominate vein, Fontan, or branch pulmonary arteries) were included. Cohort was divided into aspirin therapy alone versus advanced anticoagulation, including warfarin, enoxaparin, heparin, or clopidogrel. Primary endpoint was in-stent or downstream thrombus, and secondary endpoints included bleeding complications.
A total of 58 patients with single-ventricle circulation underwent 72 stent implantations. Of them 14 stents (19%) were implanted post-superior cavopulmonary connection and 58 (81%) post-total cavopulmonary connection. Indications for stenting included vessel/conduit stenosis (67%), external compression (18%), and thrombotic occlusion (15%). Advanced anticoagulation was prescribed for 32 (44%) patients and aspirin for 40 (56%) patients. Median follow up was 1.1 (25th–75th percentile, 0.5–2.6) years. Echocardiograms were available in 71 patients (99%), and advanced imaging in 44 patients (61%). Thrombosis was present in two patients on advanced anticoagulation (6.3%) and none noted in patients on aspirin (p = 0.187). Both patients with in-stent thrombus underwent initial stenting due to occlusive left pulmonary artery thrombus acutely post-superior cavopulmonary connection. There were seven (22%) significant bleeding complications for advanced anticoagulation and none for aspirin (p < 0.001).
Antithrombotic strategy does not appear to affect rates of in-stent thrombus in single-ventricle circulations. Aspirin alone may be sufficient for most patients undergoing stent implantation, while pre-existing thrombus may warrant advanced anticoagulation.
The oriental armyworm, Mythimna separata is an important crop pest in eastern Asia. Nocturnal insects, including nocturnal moths, have phototactic behavior to an artificial light source. Phototactic behavior in insects is species-specific in response to different wavelengths of light sources. Our previous study showed that green (520 nm) light emitting diode (LED) light resulted in a significantly higher phototactic behavior in M. separata moths compared to the other wavelength LED lights. The goal of the present study is to investigate the influence of green light illumination on biological characteristics of different developmental stages in M. separata. Our results revealed that when different developmental stages of M. separata were exposed to the green light illumination in a dark period, several biological characteristics in all developmental stages except for egg stage were positively changed, but those of F1 generation M. separata which are next generation of the adults exposed to the green light did not significantly change compared with the control level. These findings suggest that green light illumination at night (or dark period) has a positive effect on the development and longevity of M. separata.
Background: The Endoscopic endonasal approach (EEA) has become increasingly popular in the treatment of suprasellar meningiomas, which often cause visual symptoms due to compression of the anterior optic apparatus. Methods: We performed a retrospective chart review on patients who underwent EEA optic nerve decompression and resection of suprasellar meningiomas between January 1st 2005 and December 1st 2018 at McMaster University. Results: The mean age of our patients was 59.8 years. We treated 9 male and 23 female patients, with a mean follow up of 6.29 years. 23 patients (71.9%) presented with visual symptoms, with a mean duration of 8.65 months. In our patient cohort, 95.5% had stable or improved visual acuity postoperatively. Less than six months of visual decline was more likely to be associated with postoperative improvement of visual acuity, with an odds ratio (OR) of 0.0222 (95% CI: 0.0017–0.289, p<0.05); as well as visual field (OR:0.0625; 95% CI, 0.0042–0.915, p<0.05). Additionally, the absence of RAPD was associated with improved postoperative visual acuity (OR: 0.0675; 95% CI, 0.0354–0.706, p<0.05). Conclusions: Endoscopic endonasal approach can achieve good visual outcome in patients harboring suprasellar meningiomas. Symptom duration of less than six months and absence of RAPD were positive predictor of postoperative visual outcome.
Background: Canadian Stroke Guidelines recommend that Transient Ischemic Attack (TIA) patients at highest risk of stroke recurrence should undergo immediate vascular imaging. Computed tomography angiography (CTA) of the head and neck is recommended over carotid doppler because it allows for enhanced visualization of the intracranial and posterior circulation vasculature. Imaging while patients are in the emergency department (ED) is optimal for high-risk patients because the risk of stroke recurrence is highest in the first 48 hours. Aim Statement: At our hospital, a designated stroke centre, less than 5% of TIA patients meet national recommendations by undergoing CTA in the ED. We sought to increase the rate of CTA in high risk ED TIA patients from less than 5% to at least 80% in 10 months. Measures & Design: We used a multi-faceted approach to improve our adherence to guidelines including: 1) education for staff ED physicians; 2) agreements between ED and radiology to facilitate rapid access to CTA; 3) agreements between ED and neurology for consultations regarding patients with abnormal CTA; and 4) the creation of an electronic decision support tool to guide ED physicians as to which patients require CTA. We measured the rate of CTA in high risk patients biweekly using retrospective chart review of patients referred to the TIA clinic from the ED on a biweekly basis. As a balancing measure, we also measured the rate of CTA in non-high risk patients. Evaluation/Results: Data collection is ongoing. An interim run chart at 19 weeks shows a complete shift above the median after implementation, with CTA rates between 70 and 100%. At the time of submission, we had no downward trends below 80%, showing sustained improvement. The CTA rate in non-high risk patients did also increase. Disucssion/Impact: After 19 weeks of our intervention, 112 (78.9%) of high risk TIA patients had a CTA, compared to 10 (9.8%) in the 19 weeks prior to our intervention. On average, 10-15% of high risk patients will have an identifiable lesion on CTA, leading to immediate change in management (at minimum, an inpatient consultation with neurology). Our multi-faceted approach could be replicated in any ED with the engagement and availability of the same multi-disciplinary team (ED, radiology, and neurology), access to CTA, and electronic orders.
Ehrlichiosis is a zoonotic illness caused by Ehrlichia pathogens transmitted by ticks. Case data from 1999 to 2015, provided by the Missouri Department of Health and Senior Services (DHSS), were used to compare the seasonality and the change in incidence over time of ehrlichiosis infection in two Missouri ecoregions, Eastern Temperate Forest (ETF) and Great Plains (GP). Although the number of cases has increased over time in both ecoregions, the rate of change was significantly faster in ETF region. There was no significant difference in seasonality of ehrlichiosis between ecoregions. In Missouri, the estimated ehrlichiosis season begins, on average, in mid-March, peaks in June, and concludes in mid-October. Our results show that the exposure and risk season for ehrlichiosis in Missouri is at least 7 months long.