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In view of the complex wellbore dynamics associated with liquid/vapor CO2 in the Containment and Monitoring Institute (CaMI) of Carbon Management Canada (CMC) CO2 injection wellbore, a Static Gradient Survey was conducted with the focus on the verification of in-tubing pressures and temperatures at various depths in the wellbore. Specifically, the knowledge sought was to learn about the temperature profile in the regions above and below the gas-liquid interface as well as the temperature profile below the Distributed Temperature Sensing (DTS) fiber termination point in the well, where there is no temperature measurement. For the static gradient survey, four surveys (passes) were conducted over a span of 6 hours, using tandem pressure/temperature recorders. For the first and second passes, lowering and raising the wireline string in and out of the well at a steady rate was undertaken. The third pass involved stopping the gauges at specified depths for approximately 10 minutes prior to extracting them out of the wellbore. Recognizing that the responses of the gauges to temperature were much slower than to pressure, the duration of the stops varied at different depths, depending on the location of interest. The final pass took place some 6 hours after the initial run. The location of the liquid level in the well was identified, not only by the change in pressure gradients but also by a change in temperature gradients. At the gas-liquid interface, the liquid was boiling and caused localized cooling around the interface. This cooling event was registered in the DTS data where the temperature departed from the baseline temperature gradient. Another cooling event was observed near the base of the wellbore where the recorded temperature profile cooled before it again approached the normal thermal gradient. We interpreted the cause of this cooling event to be that some of the injected CO2 has migrated up-section into the shallower formation. The corresponding decrease of pressure caused a phase change and evaporation of CO2 which resulted in a reduction in the CO2 temperature. The temperature anomaly at the base of the injection well is consistent with the geophysical monitoring results from vertical seismic profiles (VSP) and the borehole electrical resistivity tomography (ERT) surveys. Understanding of the thermal processes related to Geologic Carbon Storage(GCS) is crucial for a successful deployment of projects. Our observations of temperature anomalies within the reservoir will contribute to the feasibility of employing temperature signals as a monitoring tool for the subsurface migration of the CO2 plume.

Most women develop MS before menopause. Menopausal hot flashes can worsen MS symptoms, and could be relieved with hormone therapy. Our objective was to evaluate feasibility, tolerability and symptom response of Duavee® (bazedoxifene + conjugated estrogen) in a Phase Ib/IIa double-blind randomized controlled clinical trial.We randomized 24 peri/postmenopausal women with MS and symptomatic hot flashes 1:1 to Duavee® versus placebo. Evaluations occurred at baseline and 2 months.Groups were balanced for age (mean 51.2 ± 3.6 years), EDSS [median 3 (IQR:2.5, 4.5)], and MS duration. 21/24 participants completed the study.Enrollment was protracted (34 months), partially due to concerns about hormone therapy safety.treatment group participants reported greater satisfaction and fewer missed doses; one participant (placebo) developed new MRI lesions; liver function testing remained normal for all patients.Hot Flash Related Daily Interference scale at 2 months was lower in treatment vs. placebo group [median (IQR) of 4 (0.5, 14) vs. 9 (0, 33)]. Between-group differences were not statistically significant.Despite perceived benefits in MS, estrogens have perceived risks that represent a hurdle to enrollment. With appropriate education and screening of participants, the favorable study retention (87%) and treatment satisfaction observed in the current study support the feasibility of a longer, powered trial to evaluate whether a proven treatment for menopausal symptoms, Duavee®, could also improve MS-related function in menopausal women with MS.

Background: There is an unmet need to develop therapeutic interventions directed at the neurodegeneration that underlies progression in multiple sclerosis. High-dose, pharmaceutical-grade biotin (MD1003) might enhance neuronal and oligodendrocyte energetics, resulting in improved cell function, repair, or survival. The MS-SPI randomised, double-blind, placebo-controlled study found that MD1003 improved disability outcomes over 12 months in patients with progressive multiple sclerosis. The SPI2 study was designed to assess the safety and efficacy of MD1003 in progressive forms of multiple sclerosis in a larger, more representative patient cohort. Methods: SPI2 was a randomised, double-blind, parallel-group, placebo-controlled trial done at 90 academic and community multiple sclerosis clinics across 13 countries. Patients were aged 18-65 years, had a diagnosis of primary or secondary progressive multiple sclerosis fulfilling the revised International Panel criteria and Lublin criteria, a Kurtzke pyramidal functional subscore of at least 2 (defined as minimal disability), an expanded disability status scale (EDSS) score of 3·5-6·5, a timed 25-foot walk (TW25) of less than 40 s, evidence of clinical disability progression, and no relapses in the 2 years before enrolment. Concomitant disease-modifying therapies were allowed. Patients were randomly assigned (1:1) by an independent statistician using an interactive web response system, with stratification by study site and disease history, to receive MD1003 (oral biotin 100 mg three times daily) or placebo. Participants, investigators, and assessors were masked to treatment assignment. The primary endpoint was a composite of the proportion of participants with confirmed improvement in EDSS or TW25 at month 12, confirmed at month 15, versus baseline. The primary endpoint was assessed in the intention-to-treat analysis set, after all participants completed the month 15 visit. Safety analyses included all participants who received at least one dose of MD1003. This trial is registered with ClinicalTrials.gov (NCT02936037) and the EudraCT database (2016-000700-29). Findings: From Feb 22, 2017, to June 8, 2018, 642 participants were randomly assigned MD1003 (n=326) or placebo (n=316). The double-blind, placebo-controlled phase of the study ended when the primary endpoint for the last-entered participant was assessed on Nov 15, 2019. The mean time in the placebo-controlled phase was 20·1 months (SD 5·3; range 15-27). For the primary outcome, 39 (12%) of 326 patients in the MD1003 group compared with 29 (9%) of 316 in the placebo group improved at month 12, with confirmation at month 15 (odds ratio 1·35 [95% CI 0·81-2·26]). Treatment-emergent adverse events occurred in 277 (84%) of 331 participants in the MD1003 group and in 264 (85%) of 311 in the placebo group. 87 (26%) of 331 participants in the MD1003 group and 82 (26%) of 311 participants in the placebo group had at least one serious treatment-emergent adverse event. One (

Purpose The purpose of this paper is to describe the development of Compass workers: a commissioned peer support model to support those caring for someone with dementia. Design/methodology/approach The paper offers a descriptive summary of how Compass workers came to be and is informed by consultations with key stakeholders and a service evaluation encompassing both quantitative and qualitative aspects. Findings The findings suggest that it is possible to make use of a peer support model to support those caring for someone with dementia in the context of support being provided to the cared for by statutory services. Both quantitative and qualitative data supported improvements in the quality of life for carers. Originality/value Both health and social care are facing increasing pressures. This paper offers a positive approach to addressing these pressures utilising a peer support model to support carers that may be of value to others facing similar challenges.

IntroductionFor over half a century, the Korean Peninsula has posed a foreign-policy dilemma for every American president. During this time, continuity, rather than change, has been the prevailing characteristic of U.S. foreign policy. Since President Reagan's "Modest Initiative" in 1988, the United States and the Democratic People's Republic of Korea (DPRK, or North Korea) have attempted to normalize their relations through dialogue and negotiations.1 In 1994, North Korea and the United States signed an agreement by which Pyongyang pledged to freeze and eventually dismantle its nuclear weapons program. In return, the United States pledged to provide a package of nuclear, energy, economic, and diplomatic benefits. The U.S. support of the Agreed Framework has been inconsistent. Since then North Korea has launched several rockets and missiles, and has increased its nuclear weapon arsenal. In recent years six-party talks have been used as a vehicle for change in regard to the North Korean nuclear issue. The major players-China, South Korea, Japan, Russia and the United States-have worked to collectively implement their national initiative with regard to North Korea. The result has been that these negotiations have yet to result in a concrete solution and direction for forward progression and movement. These sessions of dialogue and negotiations have proceeded without altering the underlying configuration of the United States and North Korea's Cold War postures towards each other, such as armed deterrence. Nonetheless, the persistent duality of diplomacy exercised by U.S. leaders has largely contributed to the inability to resolve their differences. The recent Bush administration, in relation to its policy towards North Korea, has been characterized by its dualism -believing in the same goal, but divided over goal achievement actions. These divisions took place within the administration, which consisted of an influential coalition of Pentagon officials and advisers, among them Secretary of Defense Donald Rumsfeld, officials of Vice President Dick Cheney's office, and proliferation experts in the State Department and White House led by Undersecretary of State John Bolton.2Unfortunately, the internal division of policy at home has resulted in the North Korean nuclear issue being in a worse shape today than it was eight years ago after the Clinton-Bush regime change. After President Bush refused to follow Clinton's engagement path, North Korea significantly increased its plutonium stockpile, tested nuclear bombs and announced itself a "nuclear weapons state." With his election as president, Barack Obama inherited not only difficult issues and initiatives on the home front but also internationally. The new Obama administration is inundated with a plethora of policy issues ranging from economics to foreign policy. President Obama has his hands full dealing with the current dismal economic situation at home and with equally important foreign policy issues, especially when it comes to North Korea.Without UN involvement, the North Korean communists held their own elections in September 1948, and under the tutelage of Russia, Kim Il Sung established the so-called Democratic People's Republic of Korea.3 Thus, the 38th parallel became Korea's "Berlin Wall." Since then, the country has been a troubled issue for every American president. Since Obama took office, North Korea has attempted to make a statement to the new president through a series of missile tests. In the past few years, many experts in North Korean policy have juxtaposed various strategies that have been used and should be included with relation to North Korea. This paper will underline motives for North Korea's actions, updates of previously communicated policy options with real-time information and offer a unique twist, with truths that are often overlooked, on how they should be implemented in the new Obama era, moving forward.North Korean MotivationSince the early 1990s, North Korea has dealt with a harsh economic and food crisis that has left the country desperate to earn hard currency. …

The Controlled High Risk Subjects Avonex Multiple Sclerosis Prevention Study (CHAMPS) showed that IM interferon beta-1a (IFNbeta-1a) significantly slows the rate of development of clinically definite multiple sclerosis (CDMS) over 2 years in high-risk patients who experience a first clinical demyelinating event. This report highlights the primary results of a 5-year, open-label extension of CHAMPS (the Controlled High Risk Avonex Multiple Sclerosis Prevention Study in Ongoing Neurologic Surveillance [CHAMPIONS Study]).To determine if the benefits of IFNbeta-1a observed in CHAMPS are sustained for up to 5 years.CHAMPS patients at participating CHAMPIONS sites were enrolled in the study. All patients were offered, but not required to take, IFNbeta-1a 30 microg IM once weekly for up to 5 years (from CHAMPS randomization). Patients who received placebo in CHAMPS were considered the delayed treatment (DT) group, and patients who received IFNbeta-1a in CHAMPS were considered the immediate treatment (IT) group. The primary outcome measure was the rate of development of CDMS. Additional outcomes included disease state classification at 5 years, annualized relapse rates, disability level at 5 years (Expanded Disability Status Scale), and MRI measures at 5 years.Fifty-three percent (203/383) of patients enrolled in CHAMPIONS (n = 100, IT group; n = 103, DT group) and 64% (32/50) of CHAMPS study sites participated in CHAMPIONS. The median time to initiation of IFNbeta-1a therapy in the DT group was 29 months. The cumulative probability of development of CDMS was significantly lower in the IT group compared with the DT group (5-year incidence 36 +/- 9 vs 49 +/- 10%; p = 0.03). Multivariate analysis suggested that the only factors independently associated with an increased rate of development of CDMS were randomization to the DT group and younger age at onset of neurologic symptoms. Few patients in either group developed major disability within 5 years.These results support the use of IM interferon beta-1a after a first clinical demyelinating event and indicate that there may be modest beneficial effects of immediate treatment compared with delayed initiation of treatment.

Objectives Multicentre randomized trials frequently encounter difficulties in meeting their recruitment targets, resulting in extension of the trial and delays in implementation of the findings. We report on recruitment strategies implemented in a randomized evaluation of computer-aided detection in women attending routine screening in the UK Breast Screening Programme. Setting The target population for the trial was identified from an existing NHS database of women aged 50–70 invited for routine mammography in Coventry, Manchester and Nottingham, UK. Women were asked to consent to their mammograms being randomly allocated (in a ratio of 28:1:1) to one of three film-reading protocols. Trial information was mailed to women, along with the invitation to attend screening, and informed consent was obtained at the mammography appointment. Several strategies were implemented to increase recruitment rates. Results Recruitment rate increased significantly over time in the study ( P < 0.0010 in all centres) with an overall acceptance rate of 46% of those attending screening. Mailing of the trial information sheet separate from the screening invitation in Coventry and Nottingham increased the recruitment rate, even after adjustment for the trend over time and for socioeconomic status of the attendees ( P < 0.001). Extension of recruitment to mobile screening units in Nottingham, and the presence of an additional member of staff also improved recruitment ( P < 0.001). Simplification of the trial information sheet had little effect. Increases in recruitment rate were not attributable to socioeconomic status of the attendees. Conclusions In multicentre trials, monitoring of local recruitment protocols is required to ensure that each centre can maximize accrual targets.

The complexity and cost of injection treatment can represent a formidable challenge for patients affected by a chronic illness, particularly those whose treatment is primarily preventative and only modestly effective on the more conspicuous symptomatic aspects of the disease process. The aim of this investigation was to identify which factors most influenced nonadherent behavior with the available diseasemodifying injection therapies for multiple sclerosis (MS). A multicenter, observational (threewave) study using surveys was developed and administered to patients with MS through the World Wide Web. Healthcare providers at 17 neurology clinics recruited patients for the study. A total of 798 patients responded to the baseline wave of the study (708 responded to all three waves). The nonadherence rates for all patients (missing one or more injections) across these waves remained relatively stable at 39 %, 37 %, and 36 %, respectively. The most common reason participants listed for missing injections was that they simply forgot to administer the medication (58 %). Other factors including injection-site reactions, quality of life, patients’ perceptions on the injectable medications, hope, depression, and support were also assessed in relation to adherence. This study characterizes factors that are associated with failure to fully adhere with disease modifying injection therapy for MS and underscores the principles associated with optimizing adherence and its implications for effective treatment of the disease process in MS.

The objective of this work was to assess the effect of interferon beta-1a (Avonex) on the rate of development of clinically definite multiple sclerosis and brain magnetic resonance imaging changes in subgroups based on type of presenting event, baseline brain magnetic resonance imaging parameters, and demographic factors in the Controlled High-Risk Subjects Avonex Multiple Sclerosis Prevention Study (CHAMPS) trial. After the onset of a first demyelinating event, 383 patients with brain magnetic resonance imaging evidence of subclinical demyelination were treated with corticosteroids and randomly assigned to receive weekly intramuscular injections of 30 microg interferon beta-1a or placebo. The treatment effect within subgroups was assessed in proportional hazards models both for the development of clinically definite multiple sclerosis and for a combined outcome of development of clinically definite multiple sclerosis or >1 new or enlarging T2 lesions on brain magnetic resonance imaging. A beneficial effect of treatment was noted in all subgroups evaluated. Adjusted rate ratios for the development of clinically definite multiple sclerosis in the optic neuritis, brainstem-cerebellar, and spinal cord syndrome subgroups were 0.58 (p = 0.05), 0.40 (p = 0.03), and 0.30 (p = 0.01) and for the development of the combined clinically definite multiple sclerosis/magnetic resonance imaging outcome were 0.50 (p < 0.001), 0.41 (p = 0.001), and 0.40 (p = 0.004), respectively. A treatment benefit on both outcome measures also was seen in subgroups based on baseline brain magnetic resonance imaging parameters, gender, and age. Interferon beta-1a is beneficial when initiated at the first clinical demyelinating event in patients with brain magnetic resonance imaging evidence of subclinical demyelination. The beneficial effect is present for optic neuritis, brainstem-cerebellar syndromes, and spinal cord syndromes.

Ictal aphasia in adults is a rare phenomenon, with the majority of reported cases showing a nonfluent Broca's or mixed aphasic speech pattern associated with disturbances of level of consciousness. There is usually only one prolonged episode of aphasia with evidence of lateralized neurological findings and structural pathology on CAT scan. We describe a patient with intermittent episodes over a 10-year period of a fluent Wernicke's aphasia associated with paroxysmal posterior temporoparietal spike-wave activity on the EEG. Interictally, the patient was clear of neurologic signs and symptoms. These episodes were repeatedly misdiagnosed as psychotic breaks and treated with antipsychotic medication and psychiatric hospitalization. Unless language performance is assessed, these cases of focal epilepsy may be diagnosed as schizophrenic "word-salad," leading to delay of appropriate treatment.

Twenty-four anxious dental patients requiring emergency extractions for the relief of pain were offered inhalation sedation with 25 per cent nitrous oxide as an alternative to general anaesthesia. The treatment of 22 patients was successfully completed by 2 final year dental students. Twenty patients (83 per cent) expressed a marked preference for the technique rather than general anaesthesia which they had also experienced.

Autosomal dominant motor system degeneration has been described primarily in Portuguese families from the Azorean Islands. The symptoms include various combinations of ataxia, pyramidal and extrapyramidal signs, appendicular dystonias, tics, ophthalmoplegias, and peripheral neuropathies with amyotrophy. One non Portuguese, non-Azorean black family has been described previously; this report describes a second such family affected by autosomal dominant motor system degeneration.