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Schizophrenia and Schizoaffective Disorders > Psychotic Disorders
Efficacy and Safety of a 2-Month Formulation of Aripiprazole Lauroxil With 1-Day Initiation in Patients Hospitalized for Acute Schizophrenia Transitioned to Outpatient Care: Phase 3, Randomized, Double-Blind, Active-Control ALPINE Study
Peter J. Weiden, MDa,*; Amy Claxton, PhDa; Jelena Kunovac, MDb; David P. Walling, PhDc; Yangchun Du, PhDa; Baiyun Yao, PhDa; Sergey Yagoda, MD, PhDa; Ilda Bidollari, MD, MBAa; Elizabeth Keane, BAa; and Ethan Cash, BSa
Objective: Evaluate efficacy and safety of a 2-month formulation of aripiprazole lauroxil (AL) with 1-day initiation during hospitalization for acute exacerbation of schizophrenia followed by transition to outpatient care.
Methods: The phase 3b double-blind Aripiprazole Lauroxil and Paliperidone palmitate: INitiation Effectiveness (ALPINE) study was conducted from November 2017 to March 2019. Adults with acute schizophrenia according to DSM-5 criteria were randomized (1:1) to AL (AL NanoCrystal Dispersion + oral aripiprazole 30 mg, day 1; AL 1,064 mg, day 8 and every 8 weeks [q8wk]) or paliperidone palmitate (PP 234 mg, day 1; PP 156 mg, day 8 and then q4wk) for 25 weeks. Patients remained hospitalized ≥ 2 weeks after randomization per protocol. Primary endpoint was within-group change in Positive and Negative Syndrome Scale total score (PANSST) from baseline to week 4. Secondary analyses included within- and between-group changes from baseline at various time points. Adverse events (AEs) and laboratory data were monitored.
Results: A total of 200 patients were randomized (AL, n = 99; PP, n = 101); 56.6% and 42.6%, respectively, completed the study. For AL, the mean baseline PANSST was 94.1; scores were significantly reduced from baseline at week 4 (−17.4; P < .001) and were also reduced at weeks 9 (−19.8) and 25 (−23.3). With PP, PANSST also improved significantly from baseline (94.6) at week 4 (−20.1; P < .001) and also improved at weeks 9 (−22.5) and 25 (−21.7). The 3 most common AEs over 25 weeks in the AL group were injection site pain (17.2%), increased weight (9.1%), and akathisia (9.1%). The same AEs were the most common in the PP group (injection site pain [24.8%], increased weight [16.8%], and akathisia [10.9%]).
Conclusions: AL and PP were efficacious and well-tolerated for initiating treatment of schizophrenia in the hospital and continuing outpatient treatment.
Trial Registration: ClinicalTrials.gov identifier: NCT03345979
J Clin Psychiatry 2020;81(3):19m13207
To cite: Weiden PJ, Claxton A, Kunovac J, et al. Efficacy and safety of a 2-month formulation of aripiprazole lauroxil with 1-day initiation in patients hospitalized for acute schizophrenia transitioned to outpatient care: phase 3, randomized, double-blind, active-control ALPINE study. J Clin Psychiatry. 2020;81(3):19m13207.
To share: https://doi.org/10.4088/JCP.19m13207
aAlkermes, Inc, Waltham, Massachusetts
bAltea Research, Las Vegas, Nevada
cCNS Network, LLC, Garden Grove, California
*Corresponding author: Peter J. Weiden, MD, Karuna Therapeutics, 33 Arch Street, Suite 3110, Boston, MA 02110 (pjweiden@gmail.com).
Long-acting injectable (LAI) antipsychotics provide continuous antipsychotic exposure over periods of weeks to months. It is believed that LAIs are an underused treatment option for schizophrenia.1-3 For inpatient services, starting an LAI rather than its oral counterpart may have several advantages for patients' long-term treatment plans. Once efficacy and tolerability of the LAI are established during hospitalization, the discharge plan can include continuation of the LAI during transition to outpatient treatment.1,2,4,5 One barrier to more frequent use of LAIs could be fragmentation of psychiatric services, especially between inpatient and outpatient care.6-8 Although hospitalization is an opportune time to start an LAI, other competing priorities may preclude implementation.3 Inpatient services must prioritize stabilization of acute symptoms in a relatively short time frame. These immediate concerns might distract inpatient teams from recommending or starting LAIs during this time.3 Despite these challenges, placebo-controlled studies9-11 of LAIs initiated in the hospital have shown safety and efficacy of LAIs for treatment of acute symptoms of schizophrenia.
Another challenge facing inpatient services is whether there is adequate time to fully initiate the LAI before discharge, given that the duration of short-term hospitalizations for schizophrenia treatment averages 10.5 days in the United States.12 A common initiation strategy to achieve therapeutic plasma concentrations is to use the oral antipsychotic counterpart for a prescribed period of time after the first LAI injection. However, the time needed to complete oral regimens ranges from 2 to 3 weeks and therefore extends beyond most inpatient stays.9,13,14 As a result, using oral supplementation when starting an LAI during an acute hospital stay will often result in a need to continue an oral antipsychotic after discharge, which, in turn, poses a risk of premature cessation of the oral antipsychotic before the full initiation regimen is completed. Some LAI formulations can be initiated without continued oral supplementation. Aripiprazole lauroxil (AL; Aristada; Alkermes, Inc.; Waltham, Massachusetts) and paliperidone palmitate (PP; Invega Sustenna; Janssen Pharmaceuticals, Inc.; Titusville, New Jersey) are LAIs indicated for treatment of schizophrenia in adults and can be started without need for continued oral supplementation following the first LAI injection.15,16 Both LAIs may reduce the time required to fully complete LAI initiation before discharge.
The Aripiprazole Lauroxil and Paliperidone palmitate: INitiation Effectiveness (ALPINE) study was designed to examine efficacy and tolerability of starting either AL or PP in patients with acute exacerbation of schizophrenia during hospitalization for acute phase treatment (through week 4) as well as transition to outpatient care for ongoing continuation phase therapy (through week 25). The primary objective was to evaluate efficacy of starting a 2-month AL regimen using the 1-day initiation regimen in acutely symptomatic patients at 4 weeks after initiation, with secondary efficacy endpoints at 9 weeks (corresponding with a single dose interval of the initial 2-month AL injection) and at 25 weeks (corresponding with 3 AL injections at 8-week intervals). The study included a PP arm to provide an active control for AL while avoiding use of a placebo in patients with schizophrenia in need of active medication. Secondary efficacy objectives used the same time points (weeks 4, 9, and 25) for the PP arm.
This phase 3b, randomized, double-blind, active-controlled study (Clinicaltrials.gov identifier: NCT03345979) was conducted from November 2017 to March 2019 at 16 US sites. The institutional review board/independent ethics committee for each study site approved the study protocol before patient enrollment. The study was conducted in accordance with Good Clinical Practice Guidelines and ethical principles derived from the Declaration of Helsinki. All study participants provided written informed consent before participating in study procedures.
It is widely believed that long-acting injectable (LAI) antipsychotics remain underused for the treatment of schizophrenia. One potential barrier to treatment is that starting an LAI can be a challenge in acute inpatient settings given very short lengths of stay.
The LAI aripiprazole lauroxil (AL) has a 2-month dose interval option with the 1-day initiation option. Patients started on this regimen can be discharged without a need for antipsychotic dosing for 2 months.
In this study, efficacy and safety of using 1-day initiation to start and continue patients on the AL 2-month dose interval option into outpatient treatment (total treatment time, 25 weeks) were consistent with results from previous studies of starting other AL monthly regimens using 3-week oral aripiprazole supplementation. No additional safety issues were observed, and symptoms continued to improve over 25 weeks.
Eligible patients were adults (aged 18-65 years) diagnosed with schizophrenia according to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), criteria17 (confirmed by Mini-International Neuropsychiatric Interview 7.0.2 for Schizophrenia and Psychotic Disorder Studies18) with an acute exacerbation or relapse of symptoms that began ≤ 2 months before screening and warranted hospitalization. Additional key eligibility criteria included prior history of hospitalization for schizophrenia and Positive and Negative Syndrome Scale total score (PANSST)19 of 80′ '120 (inclusive) with a score of ≥ 4 on ≥ 2 of any of the following for PANSS positive symptoms items: delusions (item 1), conceptual disorganization (item 2), hallucinations (item 3), and suspiciousness/persecution (item 6). Clinical Global Impression-Severity of Illness scale (CGI-S)20 scores ≥ 4 (moderately ill or worse) were also required.
Key exclusion criteria included current primary DSM-5 diagnosis other than schizophrenia; currently deemed to be at imminent risk of suicide; first antipsychotic treatment within the past 12 months; history of recent LAI treatment; history of treatment resistance; or history of hypersensitivity, intolerance, or inadequate response to aripiprazole, risperidone, or paliperidone.
Study Design and Treatments
The ALPINE study duration was approximately 26 weeks, with a 1-week screening period and a 25-week double-blind LAI treatment period (Figure 1). The study included an initial inpatient stay during the screening period and at least the first 2 weeks of double-blind treatment. Patients were required to stay in the hospital for ≥ 2 weeks. If doing so was clinically appropriate, patients were discharged 2 weeks after randomization but could delay discharge 1 week if needed. Post-discharge follow-up schedule began with outpatient visits at weeks 3, 4, and 5 and then changed to an every-4-weeks visit schedule until the last visit at week 25 (weeks 9, 13, 17, 21, and 25).
Inpatient LAI Initiation
Patients were randomized 1:1 to AL or PP on day 1 by interactive web response system. Before randomization (at screening), patients were stratified by prior history of exposure to aripiprazole and/or risperidone/paliperidone (stratification level 1: prior exposure to both aripiprazole and risperidone/paliperidone or exposure to none of these medications; level 2: prior exposure to either aripiprazole or risperidone/paliperidone). Those patients who had reliable histories of having received (and tolerated) both did not have any further oral antipsychotic exposure before their randomization injection visit. Those with a history of only risperidone/paliperidone exposure received oral aripiprazole 5 mg as a test dose to establish tolerability during the first 2 days of inpatient screening. Those exposed to only aripiprazole received 2 days of oral risperidone 1 mg, and those with no exposure to either received the 2 agents, 8 hours apart over 2 days. Prior antipsychotic medications were discontinued upon inpatient admission, with a washout period of 2 to 5 days.
Patients randomized to AL received the 1-day AL initiation regimen (AL NanoCrystal Dispersion [ALNCD] gluteal injection + single 30-mg dose of oral aripiprazole) with placebo deltoid injection on study day 1. The first AL 1,064-mg injection (gluteal) was administered on day 8 with a placebo deltoid injection to reflect timing of the PP initiation regimen to preserve the blind (Figure 1). The 1,064-mg AL dose was chosen because it was approved after the pivotal efficacy study9 and has the longest dose interval available among AL regimens.
Patients randomized to PP received a single PP 234-mg deltoid injection with a placebo gluteal injection and oral placebo tablet on day 1 and a PP 156-mg injection (deltoid) with placebo injection (gluteal) on day 8. After day 1, no oral antipsychotic was permitted with either treatment arm.
Outpatient LAI Treatment
After the AL 1,064-mg (gluteal) injection on day 8, AL was administered every 8 weeks (q8wk; weeks 9 and 17), with placebo injections (gluteal) administered at weeks 5, 13, and 21 to match the timing of PP injections (Figure 1) to maintain the blind.
PP 156-mg injections (gluteal) were administered q4wk after the day 8 injection (weeks 5, 9, 13, 17, and 21).
Efficacy was assessed using the PANSS at screening, randomization (day 1), day 4, weeks 1 and 2 (inpatient), and each outpatient visit. Baseline was defined as the last nonmissing assessment before the first dose of study drug on day 1. The primary efficacy endpoint was change in PANSST from baseline to week 4 within each treatment group. Secondary analyses included within-treatment group changes in PANSST from baseline to weeks 9 and 25 and between-group comparisons at weeks 4, 9, and 25. Safety and tolerability endpoints included incidence of adverse events (AEs), serious AEs (SAEs), and AEs leading to discontinuation. Additional standard safety assessments included laboratory parameters (eg, hematology, chemistry, metabolic parameters, prolactin, urinalysis), vital signs, body weight, injection site reactions, abnormal movement scales,21-23 Columbia-Suicide Severity Rating Scale,24 and side effects scales.25,26
The safety population included all patients who received ≥ 1 dose of study drug. Efficacy was assessed for all patients in the safety population with ≥ 1 post baseline PANSS assessment. No formal sample size calculations were performed. Study sites were pooled to ensure ≥ 10 patients per treatment group within each pooled site to improve estimation precision; 7 pooled sites resulted.
Change in PANSST from baseline to weeks 4, 9, and 25 was tested for AL and PP separately using 1-sample t tests (observed cases). Changes in PANSST from baseline to weeks 4, 9, and 25 were compared between treatment groups using mixed model for repeated measures (MMRM). Models included treatment, visit, treatment-by-visit interaction, baseline PANSST, stratification factor, and pooled study site as covariates and an unstructured variance-covariance matrix for within-subject variability. AEs were summarized descriptively for the first 4 weeks of treatment and cumulatively for the full treatment period (from week 0 to week 25).
In total, 200 patients were randomized and received their respective LAI initiation regimen on day 1 (AL, n = 99; PP, n = 101; Figure 2). All 200 patients were included in the safety analyses, and 195 were included in the efficacy analysis (AL, n = 96; PP, n = 99). Seventy-seven percent of patients completed the 4-week acute phase (AL, 79.8%; PP, 74.3%); 25-week completion rates were 56.6% for AL and 42.6% for PP.
The most common reasons for discontinuation in both treatment groups were withdrawal by patient, AEs, and loss to follow-up, both throughout the study (Figure 2) and among patients who discontinued during the first 4 weeks of treatment (Supplementary Table 1).
Demographic and baseline clinical characteristics were similar in both groups (Supplementary Table 2). Of the 200 patients, 162 (81.0%) had a history of prior exposure to risperidone/paliperidone, 112 (56.0%) had prior exposure to aripiprazole, and 26 (13.0%) had no prior exposure to any of these antipsychotics. Of the 99 patients randomized to the AL treatment arm, 43 were given the test dose of oral aripiprazole for 2 days and 17 were given oral risperidone for 2 days, with 12 of these patients receiving both aripiprazole and risperidone test doses. Of the 101 patients randomized to the PP arm, 45 were given the test dose of oral aripiprazole for 2 days and 21 were given oral risperidone for 2 days, with 14 of these patients receiving both aripiprazole and risperidone test doses.
A total of 138 (69.0%) of the 200 patients reported having antipsychotic exposure in the 30 days prior to the screening visit; the last antipsychotic received prior to screening is listed by treatment group in Supplementary Table 3. Overall, quetiapine was reported most commonly (18.5%), followed by olanzapine (17.0%), risperidone/paliperidone (15.0%), and aripiprazole (10.5%), with the remaining patients split between another atypical antipsychotic (4.0%) or a conventional antipsychotic (also 4.0%). Patients without any identified antipsychotic (n = 62 [31.0%]) presumably had no known exposure in the 30 days prior to screening.
Patients in the AL group achieved statistically significant improvement in PANSST from baseline to week 4, with a mean change of −17.4 based on observed cases (P < .001; Figure 3A). Continued improvement in PANSST from baseline with AL treatment was observed at weeks 9 (−19.8) and 25 (−23.3; both P < .001).
With PP, improvement in PANSST from baseline was also statistically significant at weeks 4 (−20.1), 9 (−22.5), and 25 (−21.7; all P < .001; Figure 3B).
The study was not powered to formally test between-group differences. The 95% CIs for LS mean changes in PANSST over time from the MMRM analysis overlap at each time point for AL and PP (Supplementary Figure 1). LS mean (95% CI) difference in change from baseline in PANSST with AL versus PP was 2.0 (−1.5 to 5.5) at week 4, 2.7 (−1.0 to 6.4) at week 9, and −0.9 (−5.0 to 3.2) at week 25. The 95% CIs for differences with AL versus PP all included zero.
Safety and Tolerability
Aripiprazole lauroxil adverse events. During 25 weeks of treatment, 69 (69.7%) of 99 AL-treated patients experienced ≥ 1 AE; AEs were largely mild or moderate in severity (94.2%). Most patients (57/99 [57.6%]) experienced AEs during the first 4 weeks of treatment (Table 1). AEs reported by ≥ 5% of AL-treated patients through week 25 were injection site pain, increased weight, akathisia, headache, and schizophrenia. The 3 most frequently reported AEs with AL through week 25 included injection site pain (17/99 [17.2%]), which was predominantly mild (16/17) and occurred with active and placebo injections; akathisia (9/99 [9.1%]), which was also predominantly mild (8/9); and increased weight (9/99 [9.1%]), which was mild or moderate.
SAEs occurred in 8 AL-treated patients (8.1%) (Table 1 and Supplementary Table 4), and there was no trend in time on treatment to occurrence of SAEs. Ten AL-treated patients (10.1%) discontinued because of AEs. AEs leading to discontinuation in ≥ 2 patients receiving AL were schizophrenia, injection site pain (1 associated with placebo injection), and psychotic disorders.
Paliperidone palmitate adverse events. During 25 weeks of treatment, 72 (71.3%) of 101 PP-treated patients experienced ≥ 1 AE; most AEs were mild or moderate in severity (93.1%). Most patients (60/101 [59.4%]) experienced AEs during the first 4 weeks of treatment (Table 2). AEs reported by ≥ 5% of patients through week 25 with PP were injection site pain, increased weight, akathisia, headache, dystonia, and somnolence. The 3 most frequently reported AEs with PP through week 25 included injection site pain (25/101 [24.8%]), which was predominantly mild (22/25) and occurred with active and placebo injections; akathisia (11/101 [10.9%]), which was also predominantly mild (8/11); and increased weight (17/101 [16.8%]), which was mild or moderate.
Seven PP-treated patients (6.9%) experienced SAEs (Table 2 and Supplementary Table 5), and there was no trend in time on treatment to occurrence of SAEs. There was 1 SAE with fatal outcome (road traffic accident) in the PP group that was assessed as unrelated to treatment. Eleven patients (10.9%) discontinued because of AEs. AEs leading to discontinuation in ≥ 2 patients receiving PP were akathisia and dystonia (including 1 event each of dystonia and oromandibular dystonia).
Transition from inpatient to outpatient care after acute hospitalization for schizophrenia is a critical time. One in 11 schizophrenia patients discharged from a short hospital stay in the United States is readmitted within 1 week.27 This 1-week readmission rate for schizophrenia is the highest among 20 medical and mental health conditions reported27 and speaks to the need to have prospective data evaluating interventions that start in the hospital and to assess outcomes during and after transitions of care for schizophrenia.
The ALPINE study was designed to provide prospective data on efficacy and safety of LAIs for treatment of an acute exacerbation of schizophrenia, started in the hospital and continued through transition of care, well into outpatient continuation treatment. Both LAIs used in ALPINE—aripiprazole lauroxil and paliperidone palmitate—have initiation regimens that can be completed within approximately 1 week or less of treatment initiation, well within the window of most short-term acute hospitalizations for schizophrenia.12 The 4-week retention rate of up to approximately 80% indicates that both AL and PP initiated in the acute setting were efficacious and well-tolerated for most ALPINE patients and provided support through the stressful experience of transition to outpatient care. Results from ALPINE can inform inpatient and outpatient services evaluating feasibility of starting LAI antipsychotics in hospitalized patients, where acute efficacy is required but relatively little time is available to fully initiate LAIs before transition to outpatient care.
The ALPINE study provided the first efficacy data for both the 1-day AL initiation regimen and the 2-month dose interval AL option, which were approved by the US Food and Drug Administration based on pharmacokinetic and safety studies.28-30 Acute symptom improvement in ALPINE patients who initiated AL with the 1-day initiation regimen was comparable to that previously observed in a pivotal study9 using 21-day oral aripiprazole supplementation. Turning to efficacy of the 2-month AL regimen, the trajectory of PANSST for the 1,064-mg dose continued every 8 weeks over the 25-week study was consistent with that reported with AL 441 mg and 882 mg q4wk in a previously published 12-week efficacy study9 followed by a 52-week safety study31 in which patients started on either of these AL q4wk regimens continued that regimen for up to 64 weeks. Similarly, the PP initiation regimen also effectively reduced symptoms of schizophrenia acutely, with durability of effect during continuation treatment consistent with that reported in previous studies.32-34
Concerns about safety of discharging patients on treatment with an LAI, or about potential safety issues developing after discharge, may be factors in clinicians' hesitation to prescribe LAIs in acute hospital settings.3,35 In ALPINE, safety findings for AL and PP throughout the study were consistent with the known profiles of each of these LAIs and the respective oral formulations, indicating tolerability through transitions of care.9,11,36-40 The most frequent AEs (≥ 5%) in the AL group (injection site pain, increased weight, akathisia, headache, and schizophrenia) were among those previously reported for acute treatment with monthly AL 441-mg and 882-mg regimens.9,15,36 Similarly, the most common AEs (≥ 5%) for patients in the PP group (injection site pain, increased weight, akathisia, headache, dystonia, and somnolence) were in line with other published PP trials.32-34 For both treatment arms, most AEs (including injection site pain and first instances of akathisia) occurred during the first 4 weeks after LAI initiation. These results support published findings41-43 that tolerability of atypical LAIs is consistent with that of the respective oral formulations and indicate that starting an LAI in the hospital does not seem to pose any additional safety risks after discharge for either AL or PP above and beyond their oral counterparts.
There are several important limitations of the ALPINE study. The study was not designed as or powered for a direct comparison between AL and PP. The purpose of the blinded PP arm was to provide an active control with known efficacy; the primary efficacy outcome was therefore within-group changes from baseline. The absence of a placebo arm limits interpretation of efficacy findings. The nature of a phase 3b clinical trial limits generalizability of the findings to the broader hospitalized schizophrenia population starting LAIs; enrolling patients who consent to participate in research and excluding those with major comorbidities may introduce bias. Also, rates of successful transition and continuation of LAI after discharge in ALPINE may be higher than that observed in routine clinical care and might have been driven in part by clinical trial incentives or characteristics of enrolled patients.
As is common for long-term clinical trials in schizophrenia, there was a substantial rate of early withdrawal from ALPINE: approximately 50% of the patients discontinued before the end of the study at week 25. Despite limitations of comparing across studies, we note that the discontinuation rate of about 25% at week 4 and about 50% at week 25 in ALPINE is within the expected range for LAI antipsychotic studies.38,44-47 The nature of clinical trials is such that the persistence of treatment in clinical practice might differ—in either direction—from these retention rates. The study design was limited to only 2 LAI treatments, and the particular LAIs used are alike in not requiring oral antipsychotic supplementation beyond the first day of treatment initiation. Therefore, post-discharge results may not generalize to use of the AL 21-day oral aripiprazole supplementation option or the initiation of other LAIs requiring oral supplementation.
In addition, tolerability to oral aripiprazole and/or risperidone for those patients without prior exposure was assessed using oral test doses consisting of 5 mg/d of aripiprazole and/or 1 mg/d of risperidone during the first 2 days before randomization. This method is consistent with methods used in previous phase 3 studies with LAIs9,32; however, while this approach will allow for assessment of immediate hypersensitivity, full evaluation of tolerability can take up to 2 weeks.15,16 Further, because the fixed-dose design did not allow for dose adjustments, results may not reflect safety or efficacy results for optimized dosing. Finally, the q4wk visits and LAI/placebo injection schedule was driven by considerations regarding blinding; therefore, ALPINE results do not address potential impact of starting hospitalized patients on a 2-month AL dose interval.
In the phase 3b, randomized, double-blind ALPINE study, starting acutely symptomatic patients with schizophrenia on a 2-month dose regimen of AL with the 1-day initiation regimen demonstrated safety and efficacy consistent with that seen in prior AL studies. These findings support clinical effectiveness of the 1-day initiation regimen. Also, this study demonstrated AL efficacy and tolerability in patients discharged on the AL 2-month regimen for continuation treatment. The inclusion of PP provided an active control with known safety and efficacy that can also be rapidly initiated. Both regimens can be effectively used in patients with schizophrenia through the often challenging transition from acute hospitalization to outpatient continuation treatment.
Submitted: December 10, 2019; accepted April 3, 2020
Published online: May 19, 2020.
Potential conflicts of interest: Dr Weiden is a former employee of Alkermes, Inc., and may own stock/options in the company. Drs Du, Yao, Yagoda, Bidollari, and Claxton; Ms Keane; and Mr Cash are employees of Alkermes, Inc., and may own stock/options in the company. Dr Kunovac reports research support received from Acadia; Alder; Alkermes, Inc.; Allergan; Amgen; AOBiome; Aptinyx; Astellas; Avanir; Axsome; AZTherapies; Bayer; Biohaven; Bionomics; Boehringer Ingelheim; Braeburn; Braintree Laboratories; Forest; Lundbeck; Indivior; Intra-Cellular; Janssen; Marinus; Myovant; Naurex; Ogeda; Pfizer; ROVI; Sage; SyneuRx; Takeda; Teva; Tolmar; and Tonix and reports consulting arrangements with Alkermes, Inc.; Janssen; Neurocrine; Otsuka; Shire; and Sunovion. Dr Walling reports research support received from Novartis; Johnson & Johnson PRD; Sunovion; Janssen; Alkermes, Inc.; Allergan; Astellas; Biohaven Takeda; Otsuka; Noven; CoMentis; Intra-Cellular; Lupin; Avanir; Lundbeck; Roche; ROVI; Boehringer Ingelheim; Acadia; and Sage and consulting arrangements with Otsuka and Janssen.
Funding/support: This study was sponsored by Alkermes, Inc (Waltham, Massachusetts). Medical writing and editorial support was provided by Gina Daniel, PhD, Kathleen Dorries, PhD, and Jane Phillips, PhD, at Peloton Advantage, LLC (Parsippany, NJ), an OPEN Health company, and funded by Alkermes, Inc.
Role of the sponsor: The clinical trial was conducted by Alkermes, Inc. Employees of Alkermes, Inc., reviewed the design and analysis of this study. The authors interpreted the evidence and made the decision to submit the manuscript.
Previous presentation: SIRS Annual Meeting; April 10−14, 2019; Orlando, Florida ▪ ASCP Annual Meeting; May 28−31, 2019; Scottsdale, Arizona ▪ Psych Congress; October 3−6, 2019; San Diego, California ▪ NEI Congress; November 7−10, 2019; Colorado Springs, Colorado.
Acknowledgments: The authors thank the patients who participated in the ALPINE study and all clinical personnel. We thank Kendra Mangan of Alkermes, Inc, clinical trial manager, for her substantial contribution. Kendra Mangan is a former employee of Alkermes, Inc.
Supplementary material: See accompanying pages.
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27.Fingar KR, Barrett ML, Jiang HJ. A Comparison of All-Cause 7-Day and 30-Day Readmissions, 2014: Statistical Brief #230. October 2017. Healthcare Cost and Utilization Project (HCUP) Statistical Briefs. Rockville, MD: Agency for Healthcare Research and Quality; 2017.
28.Hard ML, Mills RJ, Sadler BM, et al. Pharmacokinetic profile of a 2-month dose regimen of aripiprazole lauroxil: a phase I study and a population pharmacokinetic model. CNS Drugs. 2017;31(7):617-624. PubMed CrossRef
29.Hard ML, Wehr AY, Du Y, et al. Pharmacokinetic evaluation of a 1-day treatment initiation option for starting long-acting aripiprazole lauroxil for schizophrenia. J Clin Psychopharmacol. 2018;38(5):435-441. PubMed CrossRef
30.Hard ML, Wehr AY, Sadler BM, et al. Population pharmacokinetic analysis and model-based simulations of aripiprazole for a 1-day initiation regimen for the long-acting antipsychotic aripiprazole lauroxil. Eur J Drug Metab Pharmacokinet. 2018;43(4):461-469. PubMed CrossRef
31.McEvoy JP, Risinger R, Mykhnyak S, et al. Durability of therapeutic response with long-term aripiprazole lauroxil treatment following successful resolution of an acute episode of schizophrenia. J Clin Psychiatry. 2017;78(8):1103-1109. PubMed CrossRef
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33.Bossie CA, Sliwa JK, Ma YW, et al. Onset of efficacy and tolerability following the initiation dosing of long-acting paliperidone palmitate: post-hoc analyses of a randomized, double-blind clinical trial. BMC Psychiatry. 2011;11(1):79. PubMed CrossRef
34.Fu DJ, Bossie CA, Kern Sliwa J, et al. Paliperidone palmitate versus risperidone long-acting injection in markedly-to-severely ill schizophrenia subjects: onset of efficacy with recommended initiation regimens. Clin Schizophr Relat Psychoses. 2014;8(2):101-109, 109A. PubMed CrossRef
35.Geerts P, Martinez G, Schreiner A. Attitudes towards the administration of long-acting antipsychotics: a survey of physicians and nurses. BMC Psychiatry. 2013;13(1):58. PubMed CrossRef
36.Nasrallah HA, Aquila R, Du Y, et al. Long-term safety and tolerability of aripiprazole lauroxil in patients with schizophrenia. CNS Spectr. 2019;24(4):395-403. PubMed CrossRef
37.Gopal S, Hough DW, Xu H, et al. Efficacy and safety of paliperidone palmitate in adult patients with acutely symptomatic schizophrenia: a randomized, double-blind, placebo-controlled, dose-response study. Int Clin Psychopharmacol. 2010;25(5):247-256. PubMed CrossRef
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Gravity Forms User Registration Add-on Support: Users Insights automatically detects the custom user meta fields and makes these fields available in the user table and filters.
General Gravity Forms Support: Provides the tools to filter the WordPress users based on the forms submitted. Also lists the submitted form entries for each user in the user profile section.
With the Gravity Forms User Registration Add-on you can create custom forms that can be used as user registration or user update forms. The user registration/update form can contain various fields – you can choose from all the available Gravity Forms fields.
The Gravity Forms module of Users Insights lists all the Gravity Forms user data on the user table and makes it available in the user filters. Users Insights detects all the registered custom user fields and since there are different types of fields available, it also makes sure to provide the corresponding filtering options for each field.
The drop down and radio button fields allow the users to select one option from a predefined set of options.
For this type of fields, Users Insights automatically detects the available options and makes them available in the filters. In this way, when filtering the users by those fields, you can just choose from the list of available options instead of having to remember the exact names of the options.
The Checkboxes and Multi-Select fields allow the users to select one more options from a predefined set of options. The List field allows the user to add a list of one or more items. The common between these three field types is that they can store one or more options per field.
Users Insights also supports the Date field type, which means that when a Gravity Form user date field is detected and added to the table, you can sort the users based on this field in a chronological order. You can also apply various date filters based on those fields to narrow down your user selection. The values stored in the date fields are listed in the user table in a user friendly format – this is the format that you have chosen as standard date format for your WordPress install.
The rest of the Gravity Form field types, such as Text, E-mail or Phone fields are detected as text fields. The values of these fields are listed just in the format in which they are saved and you can sort the user table based on any of these fields in an alphabetical order. You can also apply various text search operators, such as "contains" or "starts with" to find all the users that fulfill a certain criteria.
The user profile section of Users Insights is the single place that collects all the available user data from different modules, plugins and elements, neatly organised to give you insights about each user's data and activity. Besides the Users Insights user table, all of the custom user fields registered with the Gravity Forms User Registration Add-on, are also available in the Users Insights user profile section. This makes it easy for you to review all of the stored Gravity Forms user data, as well as view the additional user data, such as the user location or user activity.
If you have Gravity Forms forms that are submitted by your WordPress users, you might also want to have an insight on how they interact with the forms. The Gravity Forms module of Users Insights can give you the information about who has or hasn't completed a certain form and also can provide you a detailed list with the form submissions for each WordPress user.
Once the Gravity Forms module of Users Insights is activated, it will automatically add two additional filters to the Users Insights filters section – "Has completed form" and "Has not completed form". As their names suggest, when using the "Has completed form" form filter, you can list all the WordPress users that have completed a certain Gravity Form. On the other hand, the "Has not completed" form filter lists all the WordPress users that haven't completed a particular form. Both filters give you the options to choose from one of the existing forms.
Here is an example where we have filtered the WordPress user list, showing only the ones who have completed our "Feature Requests" form.
In the same way you can also use the "Has not completed form" filter to find all the users who haven't completed a particular form. In this way, if for example you have a form that is very important to be completed by all users, you can find all the users that haven't submitted this form and export their e-mails in a CSV format by using the Users Insights export feature. Then you can use your favourite e-mail marketing tool to import the users (if it supports CSV import) and send emails to those users to remind them about the form.
In addition to the form filters, you can also see a detailed list of all form submissions for each user in the Users Insights user profile section. The submissions are listed separately for each form – the list includes the most recent submissions with a link to the Gravity Forms page where you can review the full list of submissions for the user. Each entry is represented by the date it was submitted and also includes a link to the detailed Gravity Forms entry page.
Users Insights provides many additional features – from various 3rd party plugins support to custom Users Insights specific features, that help you better organise and manage your WordPress users. The plugin is modular, which means that all the main features are available as separate modules, which can be optionally enabled or disabled. Moreover, you can customise the Users Insights user table, so it shows only the user fields that you need and in the order that you specify.
When using the Gravity Forms module of Users Insights, you are not limited to the features that this module provides – you can use the Gravity Forms features in a combination with all the existing Users Insights modules and features. For example, you can use the Geolocation feature to find out more about your users' locations. Or you could use the Groups feature to create custom user groups and assign them to your users. Additionally, if you are using any of the supported 3-rd party plugins, such as WooCommerce or Ultimate Member, you can combine the data that they generate with your Gravity Forms user data and use all the available user filters.
Another useful feature of Users Insights that you can use in combination with the Gravity Forms module is the Export feature. The Export feature lets you create a customised user data export in a CSV format. With this feature you can export the data just in the way it is presented on WordPress user the table, including all of the applied filters, visible columns and sorting options.
This feature can be very useful to export a customised user list to your favourite email marketing tool (such as export to Mailchimp), build custom reports or just to have it for a future reference.
If you need to analyze your Gravity Forms user data further, you can also use the Gravity Forms Reports feature. The reports create various charts to visualize the user data submitted with the User Registration add-on.
Whether you use the Gravity Forms User Registration Add-on to register and save custom user data, or just the Gravity Forms plugin by itself, if you have registered WordPress users that interact with these forms, you will always need a way to manage this data so you can know more about the WordPress user activity on your site. Users Insights can give you the tools to analyze, search and filter your user data and their related Gravity Forms activity.


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Q: Is anyone using node.js with an OAuth2.0 authentication system? Is there an OAuth2.0 library for Node.js, which is being used (or planned to be used) in a live, production system?

A: node-oauth provides some support for Oauth2.
"Also provides rudimentary OAuth2 support, tested against facebook connect and github. For more complete usage examples please take a look at connect-auth (http://github.com/ciaranj/connect-auth)"  taken from https://github.com/ciaranj/node-oauth

A: node-oauth is generally a good bet.

redpajama_set_name: RedPajamaStackExchange


ZIZ News…Feb 18 2012 — Quick work by the Criminal Investigation Department has resulted in the arrest of two persons within twenty four hours for the latest homicide.
In a release issued on Saturday it said in accordance with its mission of preventing crime and bringing to justice those who break the law The Royal St. Christopher and Nevis Police Force have laid formal charges on both Sylvester Crossley and Vance Thomas of Fort Thomas Road for the Murder of Miguel Robinson of Trafalgar Village.
Inspector Smithen in his quest to maintain the confidence of the General Public within the Criminal Investigation was able to ensure that such charges were preferred within 20 hours of this tragic event.
The Commissioner of Police acknowledges the hard work of the officers involved in the investigation but would like to publicly acknowledge you the general public for your support as without such support that you have given to us in our philosophy to regain the streets of the Federation our success would not become a reality.
As we continue to be united on our success we urge you the public to remain cognizant of the personal safety and security tips previously published and we do look forward to your continued support in other matters under investigation within the Federation at this time.
Meanwhile the Royal St. Christopher and Nevis Police Force has identified and is actively seeking a person of interest for questioning in connection with the reported incident which occurred at Justice Breyer's Home in Golden Rock, Nevis, on Thursday, February 9, 2012.
The individual is identified as one Vedel K. Browne of Webbes Ground in Gingerland, Nevis. He is a male, height 5′ 11″ and a gardener by occupation. If you have any information about the whereabouts of the subject or that which may be of assistance in this case, please contact Sgt. Alonzo Carty of the Nevis CID at 469-5391.
According to a Police release, any person found assisting, comforting, receiving or otherwise relieving this person of interest will be prosecuted in accordance with the law.
Investigations into this incident are ongoing. Further information will be provided as it becomes available.


text:
Different options for Free Translation APIs
=============

http://api.yandex.com/translate/ - 10 million limit per month

http://itranslate4.eu/en/api/docs - Paid per character, free 10000 words trial

https://developers.google.com/translate/ - paid service

http://www.microsoft.com/translator/translator-api.aspx - paid service

redpajama_set_name: RedPajamaGithub


text:
Asustek's new Eee PC to sport multitouch trackpad
By Dan Nystedt
IDG News Service |
The next generation of Eee laptop PCs from Asustek Computer Inc. will come with multitouch trackpads, larger screens, better webcams and increased data storage capacity, a company representative said today.
The Eee PC 900 boasts an 8.9-in. screen, compared with a 7-in. display on the original Eee PC 701, plus a 1.3-megapixel camera and a 12GB solid-state disk drive (SSD). The webcam on the Eee PC 701 is only a 0.3-megapixel model, and the largest SSD available on a 701 is 8GB.
The Eee PC 900 also has an oversized touchpad that's similar to the Macbook Air's touchpad in terms of the way it operates. Using two fingers, a person can zoom in and out of documents and photos, scroll up or down, and more, according to an Asustek representative.
A picture of the Eee PC 900 can be found on the Federal Communications Commission's Web site, where details were submitted for approval by the U.S. government regulator.
Despite some news reports saying otherwise, the Eee PC 900 won't have a touch screen or GPS technology, the Asustek representative said.
The Eee PC 900 will come preloaded with either Windows XP or Linux operating systems, the representative said.
The first devices will likely hit some markets by June. Pricing will vary by country, but in Europe, the new Eee PC will cost around €399 ($626 U.S.).

redpajama_set_name: RedPajamaCommonCrawl


The 114 series jig hooks are similar to the 604 but feature a lighter wire making them perfect for an array of techniques. Gamakatsu's 90 Degree Round Bend Jig Hook is the perfect blend of shaft length, gap, sharpness and strength so you get more out of your finished jigs and better results on-the-water! NS Black Finish.
They are constantly sharp and dependable.


This is a guest post from a local rifle training company Black Hat Training Corps.
They have put together a great guide for everyone out their searching for a good range to zero their weapon. This is another page that will be added to my guide index, and it will help many new shooters understand why the 200 yard zero makes so much sense. Click Here.


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> Work gets underway on £5.7million creative arts hub
Work gets underway on £5.7million creative arts hub
By Reporter - 3rd January 2018
Delighted Audrey Carlin from WASPS
Plans to create a £5.7million arts hub in the Highlands have been welcomed.
Members of the arts community are delighted by the news of the start of a project to give the Highlands its first creative hub as a 'game-changer'.
The initial £1.2 million project is the first phase of a wider £5.7 million scheme to transform the Midmills buildings (once part of the Inverness Royal Academy and later Inverness College but now empty) into a new Inverness Creative Academy.
Work on one building is due to start early in 2018, providing high quality, affordable workspaces for 39 artists and makers is expected to be complete by the summer of 2018.
Wasps Artists Studios – Workshop and Artists' Studio Provision Scotland and established in 1977 – which is leading the project, is also fundraising for work on a second building which would provide exhibition, performance and events space, a public café, workshop areas and offices for business working in the creative industries.
Matt Sillars, who will be running a community-based photographic initiative called the Inverness Darkroom at Midmills, said: 'The arts community has been hoping that Wasps would set up a major centre in Inverness for years, so the enthusiasm was overwhelming when it was announced.'
The message was reinforced by Kirsten Body, a member of the local Arts Steering Group, who said: 'I was involved in the initial demand study for a creative hub in 2015 and was struck by the responses we got – there is a desire to feel part of a wider creative community and for the possibility of more collaboration with other creative professionals.
'There is undoubtedly a strong need for a focused, vibrant space where people can come together to share ideas.
Matt Sillars (right) will be running a community-based photographic initiative
'I'm really keen to see this new hub as a place that caters for events, provides networking opportunities as well as a gallery space for emergent contemporary artists to showcase their work and take risks. The Midmills building has huge potential to function as a production centre and true meeting place highlighting the wealth of creative talent from our area.'
Lindsay Dunbar, of rural theatre innovators Play Pieces Arts, said: 'I really welcome the exciting development of the Creative Academy. Play Pieces Arts has run a successful programme of events in Inverness throughout the years however we are often placed in a vulnerable position due to venue availability as well as limited capacity spaces.
'The creative industry hub, as well as potential performance space, would be a game-changer for not only Play Pieces Arts but for the emerging and established makers of all art forms who want to base themselves in the Highlands.'
As one of the largest developments of its kind outside the Central Belt the Creative Academy is expected to play a valuable economic role by supporting jobs and providing new business opportunities.
Tenants could include everything from visual artists, theatre groups and craft makers to media companies or businesses at the cutting edge of the digital arts.
The Midmills building in Inverness
Wasps has had great success with similar hubs such as South Block in Glasgow.
The Creative Academy will be a first for the Highlands, helping the region tap into the growing importance of the creative industries, which generates £3.7 billion a year for the Scottish economy and provides 73,600 jobs.
This is in line with HIE's ambition for the creative sector to account for 7% of the economic activity – equaling the Scottish average.
Audrey Carlin, Wasps chief executive officer, said: Scotland is a powerhouse for the arts, craft making and the wider creative industries.
'But people wanting careers, or to build businesses, in these sectors have faced major obstacles in the Highlands because of an acute shortage of quality workspace and of hubs that allow them to collaborate and generate new ideas.
'The Creative Academy has a great deal of support from the large creative community in and around Inverness.
'We are very proud that this will be one of the largest projects of its kind in the whole of Scotland and we hope it will enable creative people from all across the Highlands fulfill their ambitions and dreams.'
An artist's impression of the atrium section of the building
The project supported by The Highland Council, HIE, Creative Scotland, Inverness City Heritage Trust and McCarthy and Stone Retirement Lifestyles Limited.
The phase one work is being carried out by Elgin-based Robertson Northern.
James Gibbs, area manager for HIE, said: 'Wasps is a social enterprise with an excellent track record of bringing economic benefit to cities. This facility will allow workers in the creative industries sector to share skills and ideas and promote collaboration and innovation.
'HIE assisted Wasps' development to help grow a strong creative cluster in Inverness and bring new economic activity to the city centre.'
Clive Gillman, director, creative industries at Creative Scotland, added: 'Wasps have built a strong sustainable model for supporting our creative communities the length and breadth of Scotland. We are proud to have helped them on that journey and especially through partnerships such as that in Inverness, which will see a significant building brought back to life to support the rich creative community in and around the city of Inverness.'
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New exhibition has been created on the fly
An exhibition that will catch the eye is opening in Edinburgh this weekend. Read More
Nicola Benedetti to perform at the Grammys Premiere
Scots violinist Nicola Benedetti is to perform at the Grammy Awards Premiere Ceremony next weekend. Read More
Artist Alec Galloway has a heart of glass
The colourful creations of legendary stained glass artist Alec Galloway are admired across the world from Ayrshire to the Emirates. Read More
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Kids and teens are constantly changing. They grow up quickly and before you know it, your giggly, energetic toddler is a teenager who sleeps until noon. As we grow, it's normal to change as we learn new things and our bodies transform into our adult selves. But with all these changes going on, how can we tell which changes are normal? At what point should we start worrying that our child's tantrums or teenager's mood swings are more than just "growing pains?" It can be hard to tell. The truth is, for many kids, these sudden changes aren't just a part of growing up—they're symptoms of a mental illness.
Could my child have a mental illness?
Anxiety disorders are the most common illness to affect children and youth. About 6% of kids experience an anxiety disorder at some point. Anxiety disorders can cause kids to be extremely afraid of things or situations to the point that it interferes with daily life.
Attention-deficit/hyperactivity disorder (ADHD) affects just under 5% of BC children at any given time. ADHD makes it very difficult for kids to focus their attention. A child with ADHD is also more impulsive and harder to settle down than other children.
Conduct disorder affects about 3% of BC children. It leads children to be extremely aggressive and destructive toward other people, pets or property. They may also seem like they don't care about important but basic rules, such as by doing things like regularly skipping school or running away from home.
Depression is a mood disorder that shows up most often during the teenage years. About 3.5% of young people in BC experience depression. Depression can affect a child or youth's attitudes and emotions, making them feel unusually sad or irritated for more than two weeks at a time.
Psychosis is a condition that involves loss of contact with reality. It affects 3% of the total population but most often appears later in adolescence and early adulthood. It can be seen on its own or with many of the illnesses mentioned in this info sheet.
Bipolar disorder is a mood disorder that may affect up to about 1% of young people. It usually starts during the teenage years, but in rare cases, it may be seen in younger children. Bipolar disorder can cause a young person's moods to change back and forth between extremely high moods, called mania, and extremely low moods, called depression.
Eating disorders are less common in young children, but the risk increases with age. Anorexia affects up to 1% of young males and females aged 15-24, and bulimia affects up to 3% of young people in Canada. Eating disorders involve a distorted body image along with seriously harmful behaviours to manage food and weight, making it difficult to nourish oneself properly.
Schizophrenia affects about 1% of the total population, and usually shows up between the ages of 15 and 25. Schizophrenia makes it hard for people to think and speak in an organized way. It can also cause people to lose touch with reality.
Suicide often goes alongside a mental illness. Suicide continues to be the second leading cause of death among 15 to 24 year-olds in BC, after motor vehicle accidents. Suicidal thinking or attempts are also common. A BC survey found that in one year, 5% of youth had made a suicide attempt and 12% seriously thought about suicide.
Started avoiding places or situations that others don't routinely avoid?
Recently complained of physical problems like frequent headaches or stomach aches, problems eating or sleeping, or a general lack of energy?
Started suddenly keeping to themselves?
Started to use (or is using more) alcohol or other drugs, especially when alone?
Shown signs that they're having trouble coping with regular activities and everyday problems?
Shown little regard for the feelings or property of others?
Expressed terror or disgust over their weight, or changed how they eat, in unhealthy ways?
Started making odd or repetitive movements beyond regular playing?
Deliberately hurt themselves or talked of suicide?
If your child is showing one or more of these changes, and it's impacting their daily life, the best thing to do is talk to them about how they're feeling and then talk to your family doctor to rule out other explanations. Then, it's important to connect to other supports in the school and community. Keep in mind that all talk of suicide must be taken seriously.
Unfortunately, only one in four kids and teens in Canada who need mental health treatment can get it. There are many reasons for this. Parents and caregivers can have mixed feelings about getting their children help for their mental illness. They may worry about being blamed for their child's change in behaviour, or they worry about what treatments may be tried. Mental illnesses can be frightening, and many people worry what others will think if they talk about their experiences. The good news is that mental illnesses can be treated successfully, and early treatment can help reduce the impact of a mental illness on your child's life. The kind of treatment that works best for your child will depend on your child's needs. Talk to your doctor to learn more about the different options.
Family therapy—Can help you look at what you can do as a family to help your child through their mental illness, and manage behaviours.
Interpersonal therapy—Helps young people to feel more comfortable interacting with others.
Educational interventions—Can help your child by teaching them ways to manage the time in the classroom.
There many different types of medications that are being prescribed to kids including medications for mood, for anxiety, for psychosis, and for ADHD. If you aren't comfortable with your child taking medications, then express your concerns to your doctor. They can explain which medications, if any, would be right for your child and go over the benefits and risks of medications with you. For young people, medications are usually not the first type of treatment considered. If they're suggested, they are usually meant to work in connection with other treatments or supports.
Visit www.familysmart.ca or call 1-855-887-8004 (toll-free in BC) or 604-878-3400 (in the Lower Mainland) for information and resources that support parents of a young person with mental illness.
Visit www.heretohelp.bc.ca for info sheets on child and youth mental health problems and helpful tip sheets on finding help and what to expect when you do find help for your child. Some of these sheets are also available in Chinese and Punjabi. Also see our Family Toolkit it's full of information, tips and self-tests to help you support a family member with a mental illness. It includes a special section on supporting a young person.
Visit www.anxietybc.com or call 604-620-0744 for information, tools, and community resources on anxiety. You'll find resources for parents of children who experience anxiety problems, including video, information, strategies to try at home, and tips for talking about anxiety with children. You'll also find AnxietyBC Youth, a site for young people. For AnxietyBC Youth, visit youth.anxietybc.com.
Visit www.youthinbc.com for youth resources and support. They are trained to help with crisis situations like suicide and other difficult situations. Call 1-866-661-3311 (toll-free in BC) or 604-872-3311 (in the Lower Mainland) 24 hours a day to talk by phone, or chat online at www.youthinbc.com between noon and 1.00 am Pacific Time.


SUPERIOR QUALITY LAMPS ENGINEERED FOR DIVERSE APPLICATIONS.
We supply Heraeus - Amba medium pressure UV lamps manufactured from the highest quality quartz glass which enables high levels of UV radiation to be transmitted. The seal is formed using molybdenum foil with platinum which ensures good life even at very high operating temperatures and currents, and the assemblies are furnace-cleaned to remove any traces of impurities. Extensive testing of each lamp and exacting manufacturing processes limits premature lamp failure to an absolute minimum.


Hi, Welcome to PK.4J.COM, the best place to play free online games on your pc, apple, android mobile and tablet. The page contains the top rated games on PK.4J.COM. Top rated games mean the best, high quality games. Enjoy the fun of playing these games with your friends. Please tell your friends about PK.4J.COM via facebook, twitter, google plus, youtube, instagram etc. They'll thank you.


text:
package com.abplus.qiitaly.app;

import android.app.ActionBar;
import android.app.Activity;
import android.app.ProgressDialog;
import android.content.Context;
import android.content.Intent;
import android.os.Bundle;
import android.support.v4.widget.SwipeRefreshLayout;
import android.view.Menu;
import android.view.MenuItem;
import android.widget.ListView;
import android.widget.SearchView;
import android.widget.TextView;
import butterknife.ButterKnife;
import butterknife.InjectView;
import com.abplus.qiitaly.app.utils.Dialogs;

/**
 * 検索結果のアクティビティ
 *
 * Created by kazhida on 2014/08/13.
 */
public class SearchResultActivity extends Activity {
    @InjectView(R.id.title_text)
    TextView titleText;
    @InjectView(R.id.swipe_layout)
    SwipeRefreshLayout swipeLayout;
    @InjectView(R.id.list_view)
    ListView listView;

    private static final String QUERY = "QUERY";
    private ArticleListAdapter.BySearch adapter;

    public static Intent searchIntent(Context context, String query) {
        Intent intent = new Intent(context, SearchResultActivity.class);
        intent.putExtra(QUERY, query);
        return intent;
    }

    @Override
    protected void onCreate(Bundle savedInstanceState) {
        super.onCreate(savedInstanceState);
        setContentView(R.layout.activity_search_result);
        ButterKnife.inject(this);

        String query = getIntent().getStringExtra(QUERY);

        ActionBar actionBar = getActionBar();
        assert actionBar != null;
        actionBar.setDisplayHomeAsUpEnabled(true);

        adapter = new ArticleListAdapter.BySearch(this, query);

        setTitle(getString(R.string.search_result_title, query));
        titleText.setText(getString(R.string.search_result_for, query));
        listView.setAdapter(adapter);

        swipeLayout.setOnRefreshListener(new SwipeRefreshLayout.OnRefreshListener() {
            @Override
            public void onRefresh() {
                adapter.reload(new Runnable() {
                    @Override
                    public void run() {
                        swipeLayout.setRefreshing(false);
                    }
                });
            }
        });
    }

    @Override
    public boolean onCreateOptionsMenu(Menu menu) {
        getMenuInflater().inflate(R.menu.search, menu);

        SearchView searchView = (SearchView) menu.findItem(R.id.action_search).getActionView();
        searchView.setQuery(adapter.getQuery(), false);
        searchView.setOnQueryTextListener(new SearchView.OnQueryTextListener() {
            @Override
            public boolean onQueryTextSubmit(final String query) {
                setTitle(getString(R.string.search_result_title, query));
                titleText.setText(getString(R.string.search_result_for, query));

                final ProgressDialog dialog = Dialogs.startLoading(SearchResultActivity.this);
                adapter.reload(query, new Runnable() {
                    @Override
                    public void run() {
                        dialog.dismiss();
                    }
                });
                return true;
            }

            @Override
            public boolean onQueryTextChange(String newText) {
                return false;
            }
        });

        return true;
    }

    @Override
    public boolean onOptionsItemSelected(MenuItem item) {
        switch (item.getItemId()) {
            case android.R.id.home:
                finish();
                return true;
            default:
                return super.onOptionsItemSelected(item);
        }
    }
}


With its sleek and contemporary design, the Destroyer pool table blends modern style with quality construction and unmatched play-ability. Built with solid wood top rails for added durability and a built-in ball storage alcove.
This high-styled Legacy Billiards table will be the centerpiece of your home game room for years to come.


Private property on Just over 10 acres with approx. 1.5 acre Pristine spring fed small lake! Beautiful Hilltop perfect for a homesite with mountain views of the national Park! You will be looking right at the famous Mount LeCont! Slightly rolling and Easy to walk. Absolutely fantastic location, About seven minutes from downtown Sevierville and 10 minutes the back way to pigeon Forge. Easy drive with no windy or curvy roads. Lots of beautiful hardwoods, evergreens adorn the rolling hills. It is actually two separate deeded parcels being sold together. Property is unrestricted meaning: you can create a farm, would be great for horses and other farm animals or just a private estate, subdivided, build multiple houses or just one fantastic one! Pond is large enough for canoeing, kayaking, or creating your own stocked fishing pond!


text:
Q: How to get a tag value from an XML in string I have the below variable declared
TEXT='<soapenv:Envelope xmlns:soapenv="http://schemas.xmlsoap.org/soap/envelope/" xmlns:v1="http://ws.chpconsulting.com/alfa/requestcontext/v1" xmlns:v11="http://ws.chpconsulting.com/alfa/user/v1"><soapenv:Header><v1:context></v1:context></soapenv:Header><soapenv:Body><v11:load><!--Optional:--><userId>IN2Z83</userId></v11:load></soapenv:Body></soapenv:Envelope>'

How to get the userID tag value in the shell script

A: Try this
 grep -o 'userId>.*</userId' | sed 's/^.*>//g;s/<.*$//g'

Demo:
$echo $TEXT
<soapenv:Envelope xmlns:soapenv="http://schemas.xmlsoap.org/soap/envelope/" xmlns:v1="http://ws.chpconsulting.com/alfa/requestcontext/v1" xmlns:v11="http://ws.chpconsulting.com/alfa/user/v1"><soapenv:Header><v1:context></v1:context></soapenv:Header><soapenv:Body><v11:load><!--Optional:--><userId>IN2Z83</userId></v11:load></soapenv:Body></soapenv:Envelope>
$echo $TEXT | grep -o 'userId>.*</userId' | sed 's/^.*>//g;s/<.*$//g'
IN2Z83
$

A: Assuming you're using a shell like bash that understands here string syntax, you can use a command-line XML tool like xmlstarlet:
xmlstarlet sel -t -v '//userId' <<< "$TEXT"

or hxselect from W3C's HTML-XML-Utils package:
hxselect -c userId <<< "$TEXT"

or another tool of your choice.
Otherwise, you can pipe the XML text to the tool:
echo "$TEXT" | xmlstarlet sel -t -v '//userId'


The girl was smart, pretty — and obsessed with the idea of taking her own life.
What drives a child to such a dark place — in which death seems the logical escape from unbearable suffering?
The answer is both terrifying and as common as homework. The teen, a student at a highly regarded New York City public middle school, was targeted for torment by a gang of Mean Girls.
Her classmates "made fun of her because she was skinny. Other girls were more developed," Bonnie Eaker Weil, Ph.D., a family therapist who counseled the teen and her parents, told me. Her folks were in denial.
The girl "cried herself to sleep every night." So the psychotherapist took it upon herself to call the principal of her patient's school.
That was nine months ago. The wicked teasing appears to have stopped before the new school year and the girl is fine physically. But she may endure permanent emotional scars.
Since the dawn of textbooks and cliques, schools have been veritable jungles in which the strong survive and the weak are preyed upon. But the rise of social media has made bullying organized and often anonymous. Education officials either have difficulty policing it — or try to ignore it altogether.
It happens in public and private schools throughout the United States and beyond, and continues in institutions of higher education. A group of male students at the elite, public Hunter College HS on the Upper East Side, which serves brainy youngsters in grades 7 through 12, behaved like gay-bashing, misogynist jerks, The Post's Selim Algar reported last week.
The Mean Guys, who call their band of idiots "MILK," have been using an online chat room to rate the looks of girls, hurl homophobic slurs and trash peers they despise, according to leaked screen shots. This, at a school overseen by the City University of New York that's typically ranked as among the top in the country, if not the best.
While some students applaud the person who exposed the chat room — dubbed "Snowden" after government leaker Edward Snowden — others aren't so sure.
Taking to Facebook like an electronic confessional, some questioned whether anyone should be punished for messages they intended to be private.
But words can maim. Hunter's acting director said school honchos are investigating whether any school regulations or policies were violated.
At least since Tyler Clementi, an 18-year-old freshman at Rutgers University in New Jersey, committed suicide by jumping off the George Washington Bridge in 2010, national attention has focused on cyberbullying and the struggles of lesbian, gay, bisexual and transgender youths. Three days before Clementi's death, his roommate, Dharun Ravi, and a female pal watched him kiss a man via a secret Web cam planted in the dorm room the two young men shared, and Ravi tweeted gossip about it.
But his convictions for a host of crimes were overturned by an appellate court, and Ravi, now 24, pleaded guilty last month to a count of attempted invasion of privacy. A judge sentenced him to no more time behind bars than the 20 days he had already served.
Is there more bullying today, or are members of the public simply talking about it more? It's unclear, but the fight against online tyranny has drawn an anti-cyberbullying campaign by former presidential paramour Monica Lewinsky.
Melania Trump said she intends to fight it if she becomes first lady after her husband's presidential election Tuesday. What irony!
She seems clueless that her hub, The Donald, infamously directed Twitter and real-world rants at folks from women to his fellow Republicans.
The latest studies reveal that about 1 in 3 American students reported being bullied at some point in the real world — through physical attacks, verbal taunts or gossip-spreading — and 43 percent said they were targeted in cyberspace.
Some admitted they participated in it.
It's time that school officials, all the way through those in colleges and universities, impress upon young people the urgent need to cut the crass acts. Cruelty can be a matter of life and death.


Mark Jones, the Joseph D. Jamail Chair in Latin American Studies, professor of political science, fellow in political science at Rice's Baker Institute for Public Policy and fellow at Rice's Kinder Institute for Urban Research, is featured in a CBS Evening News television broadcast and authored an op-ed in The Hill about the results of Texas' midterm elections. Jones is also quoted in numerous other articles about the subject.
Beto O'Rourke's coattails are long for Texas House Democrats, but do they reach to 2020?
How did straight-ticket voting affect this year's election?
Minor advances by Democrats in the Lege; how will that affect 2019 session?
The work of Josh Eyler, director of Rice's Center for Teaching Excellence, who authored the forthcoming book "How Humans Learn: The Science and Stories Behind Effective College Teaching," is featured.
Rice research that determined the structure of the condensin protein complex is featured.
Is the migrant caravan an invasion?
Gil Kerlikowske, a nonresident fellow at Rice's Baker Institute for Public Policy, is quoted in an article about a caravan of Central American migrants headed to the U.S.
An article mentions that Roger Scruton spoke at Rice in 2005.
An article about Texas midterm election results mentions that Julie Love's brother attended Rice.
Marie Lynn Miranda, Rice's Howard R. Hughes Provost and a professor of statistics, is quoted in an article about the Hurricane Harvey Registry, a joint venture of Rice, the Houston Health Department and the Environmental Defense Fund that is collecting and maintaining information from those affected by the storm, including health effects.
Vivian Ho, the James A. Baker III Institute Chair in Health Economics at Rice's Baker Institute's Center for Health and Biosciences, is featured in a "Spotlight" Q&A. A "Field Notes" slideshow features Natasha Kirienko, assistant professor of biosciences, who received a five-year grant for nearly $2 million to refine the understanding of a pathway in mitochondria that helps repair it when damaged.
Government-funded initiatives to address the overdose epidemic in the U.S. have targeted opioids and have neglected other drugs that are increasingly implicated in overdoses, according to Katharine Neill Harris, the Alfred C. Glassell III Fellow in Drug Policy at Rice's Baker Institute for Public Policy.
An article mentions that Rice is ranked No. 9 in the nation in terms of best value by WalletHub.
Ranked: America's Top 500 colleges and universities for 2019; who's No. 1?
Alumna Emily Jackson '13, who will perform Nov. 10 with the East Texas Symphony Orchestra at the University of Texas at Tyler, is featured.
A wedding photo taken in front of Rice's Fondren Library is featured in a slideshow.
Douglas Brinkley, the Katherine Tsanoff Brown Professor in Humanities, is interviewed on Katie Couric's podcast about the Nov. 6 midterm elections.
Could Mexico's new Congress really legalize marijuana?
High school students from Louisiana who are planning to tour Rice are featured.
Can TCJA save the corporate income tax?
Jorge Barro and Joyce Beebe, fellows in public finance at Rice's Baker Institute for Public Policy, co-authored an op-ed about the federal government's corporate income tax revenue.
Neal Lane, a senior fellow in science and technology policy at Rice's Baker Institute for Public Policy, is quoted.
Rice research that found a simple method to attach drugs or other substances to proteins central to the body's immune system is featured. Han Xiao, the Norman Hackerman-Welch Young Investigator and Assistant Professor of Chemistry, is quoted and pictured. Graduate student Chenfei Yu and postdoctoral researcher Juan Tang are pictured.
Postdoctoral research associate Rodrigo Salvatierra is quoted in an article about a study he co-authored that determined carbon nanotube films may extend the life of lithium batteries.
An article mentions that Rice has an emergency medical services (EMS) program that allows student volunteers to respond to campus crises and administer immediate care. Lisa Basgall, EMS director and adjunct lecturer in the kinesiology department at Rice, is quoted.
Alumna Colleen Fitzpatrick '76 is featured and pictured.
Alumnus Christopher Liu '13 is featured.
An op-ed authored by Daniel Cohan, associate professor of civil and environmental engineering, is featured.
Quinta Moore, a fellow in child health policy at Rice's Baker Institute for Public Policy, is quoted in an article about her research that determined being evicted leads to depression, poorer health and higher levels of stress, and the side effects can persist for years.
An article mentions that architect Randolph Martz attended Rice.
An article mentions Rice's Oshman Engineering Design Kitchen.
Rice's women's basketball team, which lost to Texas A&M University 65-54 in the season opener Nov. 7 in College Station, is featured.
An article features the Oracle Challenger Series tennis tournament Nov. 10-18 at Rice's George R. Brown Tennis Center.
An article mentions the Rice football team's 34-26 loss to the University of Texas at El Paso Nov. 3 at Rice Stadium.
State of the LSU offense: How do the Tigers view their offense after shutout to Alabama?
An article mentions that Louisiana State University's football team will play Rice later this season.
Rice is mentioned in a caption.
Is Bryce Callahan the most undervalued player on the Chicago Bears?
Mathematical models, including a model developed at Rice more than 15 years ago, allow scientists to calculate how well the flu vaccine matches the infecting viruses. The Rice model, called pEpitope, estimates vaccine effectiveness, and it has been shown to work well for several flu strains.


The discography of Misfits, a horror punk band formed in Lodi, New Jersey in , consists of Three of the songs from the album sessions were released as 3 Hits from Hell the Misfits recorded songs for their first full-length album Walk Among Us, including Static Age which was released as a separate album in The Misfits are an American punk rock band often recognized as the progenitors of the horror . Following the Static Age sessions, the Misfits began a shift in songwriting and appearance, Throughout the rest of they continued to record tracks for a full-length album, to be titled Walk Among Us. They had planned to. The Misfits are an American horror-themed punk rock band from Lodi, New Jersey. . Misfits - Walk Among Us album art Misfits - Earth A.D. / Wolfs Blood album art Misfits - Legacy Of Brutality album art Misfits - Static Age album art .
List of the best Misfits albums, including pictures of the album covers when available. Albums range from Walk Among Us () to American Psycho ( ) to The Devil's Static Age is listed (or ranked) 2 on the list The Best Misfits Albums. A true legacy of brutality. Misfits: Ranking All 7 Studio Albums From Worst To Best. A true legacy of brutality. Share · Tweet. Caroline Records. Misfits discography and songs: Music profile for Misfits, formed January Genres: Albums include Walk Among Us, Static Age, and Earth A.D. / Wolfs Blood.
Find Misfits discography, albums and singles on AllMusic. The 'Fits first proper live album since the 's is entombed in the ultimate .. Static Age is the only full-length Misfits album to feature the band's original the complete albums: "Collection I", "Collection II", "Legacy of Brutality", "Evilive", " Earth . Fiend Facts: "Walk Among Us" was the first full-length album to be " released". Misfits Articles and Media. Static Age. by: Maggie Serota. October 31 Misfits. Walk Among Us. by: Jason Heller. October 31 Misfits Pitchfork to Review 4 Key Albums by Misfits and Danzig. by: Sam Sodomsky. October 30 barechahariabhowna.com brings together thousands of 'greatest ever album' charts The best album by Misfits is Walk Among Us which is ranked number 1, in.


text:
Q: Android: layout issue with Image Views I am keeping three image views with 3 different images of the same height. My code is as mentioned below..
<LinearLayout
    android:id="@+id/LinearLayout06"
    android:layout_width="wrap_content"
    android:layout_height="wrap_content"
    android:gravity="left" android:layout_gravity="center_vertical|center_horizontal">

    <ImageView
        android:id="@+id/stopServiceButton"
        android:layout_width="wrap_content"
        android:layout_height="80dp"
        android:layout_weight="1"
        android:adjustViewBounds="true"
        android:background="@null"
        android:paddingRight="5dp"
        android:src="@drawable/stop_service_button_selector" />

    <ImageView
        android:id="@+id/calibrateButton"
        android:layout_width="wrap_content"
        android:layout_height="80dp"
        android:layout_weight="1"
        android:adjustViewBounds="true"
        android:background="@null"
        android:padding="5dp"
        android:src="@drawable/calibrate_button_selector" />

    <ImageView
        android:id="@+id/doneButton"
        android:layout_width="wrap_content"
        android:layout_height="80dp"
        android:layout_weight="1"
        android:adjustViewBounds="true"
        android:background="@null"
        android:padding="5dp"
        android:src="@drawable/done_button_selector" />

</LinearLayout>

In large layouts i was able to manage these images(i dont have to use weight parameter for it) but for small layout i have to keep the weight parameter as one to fit them in the screen, but then the height changes as shown below.

Can someone help me out in this ?

A: the  android:adjustViewBounds="true" preserves the aspect ratio of the images. since the width is to wrap content, the height gets reduced accordingly.

A: To reduce the blurring effect that you mentioned in your comment, you can try setting android:filter the attribute to the drawables.


text:
8yo boy becomes the first..
8yo boy becomes the first child with coronavirus in Australia
A boy in Queensland has become the first child in Australia diagnosed with coronavirus.
The eight-year-old Chinese national from Wuhan – the epicentre of the deadly outbreak – is the third confirmed case in the Sunshine State.
The child was a member of a tour group on board a Tiger Airways flight from Melbourne to the Gold Coast late last month.
Two other members of the group – a 42-year-old woman and 44-year-old man – have also been diagnosed with the illness.
He's being isolated at a Gold Coast hospital and is in a stable condition.
There are more than 20,000 confirmed cases of coronavirus globally, with the death toll now at 427.
There are 13 confirmed cases in Australia; four in NSW and Victoria, three in Queensland and two in South Australia.
Image: Getty/Mark Ralston
AustraliaHealthNewsQLD


text:
COMET helps farmers to measure carbon footprint
USDA's COMET-Farm and COMET-Planner help farmers know their farm's carbon footprint
By RM Bureau | December 5, 2015
USDA's COMET-Farm and COMET-Planner help farmers know their farm's carbon footprint.
As world leaders meet in Paris to discuss climate change, agriculture is one human activity that must be factored in—both as an emitter and an absorber of greenhouse gas. But how can farmers know their farm's carbon footprint?
USDA's COMET-Farm and COMET-Planner are the free, online tools allow farmers and ranchers to quantify their atmospheric outputs (emissions) and carbon benefits (sequestration) based on site-specific soils, crops, and management practices.
Farms have frequently been seen as sources of carbon emissions traced to operations such as tillage, fertilizing and methane from livestock. But farms also grow prodigious amounts of plant life—and that pulls carbon dioxide out of the atmosphere.
Balancing agriculture's net emissions and sequestrations has been a question mark. That's where the COMET tools come in, says Adam Chambers, one member of the team that developed the online tools. Chambers is with the Energy and Environmental Markets Team of USDA's Natural Resources Conservation Service (NRCS). NRCS joined forces with Colorado State University to build the tools. California's Department of Food and Agriculture, Marin Carbon Project and the California Farm Bureau lent their expertise to make the tools more user-friendly.
According to Chambers, farms improve their atmospheric benefits by implementing conservation practices such as reduced or no-tillage, cover crops, riparian buffers, hedgerows and more than 30 NRCS conservation practices that are "climate-smart," and can be calculated using the COMET tools. "The practices have long been recognized as good for soil, water and habitat," says Chambers, "now they are getting credit for keeping carbon (a.k.a. soil organic matter) underground too."
"Some farmers may be merely curious about their carbon footprint while others may be interested in tapping into carbon markets," says Chambers. While current prices are quite low, future conditions could change this, Chambers says. "This could be a further incentive to 'farm for carbon'."
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