Multiple sclerosis (MS) is characterized by focal inflammatory activity in the central nervous system and a diffuse, compartmentalized inflammation that is the primary driver of neuroaxonal damage and worsening disability. It is now recognized that higher-efficacy disease-modifying therapies (HE-DMT) are often required to treat the complex neuropathological changes that occur during the disease course and improve long-term outcomes. The optimal use of HE-DMTs in practice was addressed by a Canadian panel of 12 MS experts who used the Delphi method to develop 27 consensus recommendations. The HE-DMTs that were considered were the monoclonal antibodies (natalizumab, ocrelizumab, ofatumumab) and the immune reconstitution agents (alemtuzumab, cladribine). The issues addressed included defining aggressive/severe disease, patient selection of the most appropriate candidates for HE-DMTs, baseline investigations and efficacy monitoring, defining suboptimal treatment response, use of serum neurofilament-light chain in evaluating treatment response, safety monitoring, aging and immunosenescence and when to consider de-escalating or discontinuing treatment. The goals of the consensus recommendations were to provide guidelines to clinicians on their use of HE-DMTs in practice and to improve long-term outcomes in persons with MS.

This “Evaluation of China's Energy Options” (ECEO) is a very important and informative analysis of China's energy-supply challenges. The ECEO was prepared for and with the support of the China Sustainable Energy Program. The Program links American and Chinese experts and is aimed at assisting “in China's transition to a sustainable energy future by promoting energy efficiency and renewable energy.” The ECEO was itself written by an international group of experts on energy issues. They seek to augment the Chinese Development Research Centre's 2004 “National Energy Strategy and Policy 2020” (NESP), an assessment of China's current and future energy needs and how to satisfy them. The ECEO is thus a treasure trove of data and concise analyses of the structure of China's energy demand and supply as well as the relevant institutions and organizations.

On May 21, 2009, lay citizens will join professional judges in deciding the fate of suspects of major crimes in Japan's new saibanin or lay assessor system.[1] This system, laudable for pursuing public understanding and reform in a judiciary long criticized for being distant and overly bureaucratized, contains provisions that could do as much harm as good. Among causes for concern, the new law contains a harsh secrecy provision that stands out as a potential source of problems. This provision, which threatens to imprison or fine citizens who speak too freely about their service as lay assessors, will make reporting misconduct difficult and chill the public discourse that the system ostensibly aims to foster. Such secrecy may also inflict significant psychological harm upon those affected by the disturbing details of a criminal trial. These potential ramifications should be taken into consideration as Japan makes its way through this new world of lay participation.

Like great port cities throughout history, Jaffa has always welcomed strangers; enough of them to earn its sobriquet “mother of strangers” (umm al-gharīb). The gateway to Palestine and the Levant since ancient times, Jaffa is not only the site of multiple events of biblical or broader religious significance. With the incorporation of Palestine in the late 18th century into the still developing modern world system, Jaffa became a city of culture and commerce, with winding casbahs and tree-lined boulevards, Turkish baths and Jewish bordellos, sand dunes and orange orchards—lots of them, as we'll see—and some of the most striking architecture, never mind coastline, of the Eastern Mediterranean. North African Jews, Haurani Bedouins, Afghan traders, rabbis from Beirut, troubadours from Jerusalem, divas from Mansoura, and more than a few European Christian and Jewish pilgrims, all made their way to and through Jaffa over the centuries, joining a local population that septupled to over 17,000 during the course of the 19th century. They were joined by tens of thousands of Jews for whom Jaffa was a port of entry to Palestine with the onset of Zionist colonization. Jaffa, in other words, is the perfect locale for a novel, especially when, as with award-winning architect and writer Suad Amiry's first novel, Mother of Strangers, most of it happens to be rooted in truth.

OBJECTIVES/GOALS: We are launching a multi-center prospective registry for patients with metastatic invasive lobular carcinoma (ILC), the second most common type of breast cancer, to better understand patterns of progression, imaging features of metastatic sites, and if serial cell free DNA measurements can serve as a surrogate marker of disease progression. METHODS/STUDY POPULATION: Patients with biopsy proven metastatic ILC of any receptor subtype will be included in the registry. We will exclude patients with ductal histology only or those with multiple primary malignancies. Patients will be enrolled at four large academic medical centers across the country. Cell free DNA measurements using a tumor informed assay will be obtained every 3 months concurrent with regular clinical imaging. Disease status will be determined by the patient’s medical oncologist by taking into account imaging, tumor markers, symptoms, and cell free DNA measurement. At each time point, patients will be surveyed on their quality of life and their medical oncologists will be asked to rate the clinical utility of the cell free DNA value. Patients will be followed indefinitely. RESULTS/ANTICIPATED RESULTS: We will explore whether the use of serial cell free DNA or a combination of blood-based biomarkers and clinical endpoints can reliably identify treatment response and disease progression in patients with metastatic ILC. Many patients with metastatic ILC have unmeasurable disease on imaging and are thereby excluded from clinical trials. The end goal of this registry is to determine if blood-based biomarkers can be used as a proxy for measurable disease in ILC patients and therefore increase clinical trial enrollment for this subgroup of patients. DISCUSSION/SIGNIFICANCE: The creation of this prospective registry will open the door for future studies of blood-based markers that reflect disease stability and progression, which is an unmet need specifically in ILC. Identification of such markers could lead to a novel treatment response endpoint, changing the way patients are enrolled in trials and managed clinically.

Pietraszewski misrepresents both the nature of behaviour in conflict and the ability of psychology to theorise the relational properties of group designation. At the behavioural level, he focusses exclusively on “attack,” when consolation/care in conflict is equally present and important. At the theoretical level, he ignores existing psychological work on how group perception is shaped by the meta-contrast principle.

The Canadian Multiple Sclerosis Working Group has updated its treatment optimization recommendations (TORs) on the optimal use of disease-modifying therapies for patients with all forms of multiple sclerosis (MS). Recommendations provide guidance on initiating effective treatment early in the course of disease, monitoring response to therapy, and modifying or switching therapies to optimize disease control. The current TORs also address the treatment of pediatric MS, progressive MS and the identification and treatment of aggressive forms of the disease. Newer therapies offer improved efficacy, but also have potential safety concerns that must be adequately balanced, notably when treatment sequencing is considered. There are added discussions regarding the management of pregnancy, the future potential of biomarkers and consideration as to when it may be prudent to stop therapy. These TORs are meant to be used and interpreted by all neurologists with a special interest in the management of MS.