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Privately owned James Island again topped the list of South Vancouver Island's highest assessed properties, according to data from BC Assessment. (Sotheby's International Realty photo)
Seven south Island properties make list of B.C.'s top valued residences
Privately owned island at centre of lawsuit tops list, again
A handful of Greater Victoria properties made BC Assessment's list of the 500 top-valued residential properties in the province last year.
BC Assessment's 2021 report uses data on residential properties in the province as of July 1, 2020. All of the region's municipalities saw an appreciation in median property values.
The top valued Greater Victoria property was James Island off the Saanich Peninsula near Sidney – a site that's earned the top spot several times. It's also central to a lawsuit by a local First Nation. In 2018 the Tsawout Nation filed against the federal and provincial governments for the return of the island claiming it as part of an 1852 treaty.
The 770-acre property was valued at $57,980,000 in July 2020, up more than $1.2 million from the year prior. The land contains a one-storey house with four bedrooms and five bathrooms valued at roughly $6.5 million. The property's assessed value is the third highest in the province.
READ ALSO: Home values surge across Greater Victoria
A North Saanich acreage at 1850 Lands End Road valued at roughly $14 million comes in at 195 on the list. The 25-acre piece of land features a three-bedroom, three-bathroom house built in 1983. In 2020 its assessed value jumped nearly $2 million from 2019.
A single-family residence in Oak Bay comes in at 199, the property at 3160 Humber Rd. has a $13.9 million assessed value – with more than $10 million attributed to the 1.87-acre plot of land. The custom two-storey house on the property has five bedrooms and seven bathrooms. It was built in 1996.
In the Gulf Islands, an acreage on Domville Island takes spot 357 and an acreage on Forrest Island takes spot 434.
Two other Oak Bay properties made the top 500 – a 1.13-acre property at 963 Beach Dr. and a 2.2-acre property at 3150 Rutland Rd. The Beach Drive property is valued at $10.7 million and the Rutland Road property is valued at $10.8 million.
For more news from Vancouver Island and beyond delivered daily into your inbox, please click here.
READ ALSO: Don't agree on your property assessment? Here's what to do
Expectant B.C. mom dodges branches, elk and an empty gas tank to deliver New Year's baby
Returning travellers no longer eligible for the Canada Recovery Sickness Benefit: Trudeau


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Browning Funeral Home
738 Diamond Ave.
Monday, Dec. 3, 2018
St. Paul's Lutheran Church
100 East Michigan Street
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More Obituaries for Victor Schuler
Victor Schuler
Victor Elmer Schuler
Evansville, Ind.
On Friday, November 30, 2018, Jesus called Victor Elmer Schuler home to Him in heaven at Braun's Nursing Home in Evansville.
Victor was born on August 22, 1922, to the late Gale and Theodora (Wilkening) Schuler in Thawville, Illinois. He was baptized into Christ at St. Paul's Lutheran Church in Woodworth, IL. Victor was drafted into the U.S. Army in 1945 and, because of his fluency in German, Victor served as a special agent in the Army's Counterintelligence Corps in Germany during WWII. Victor was a graduate of University of Evansville where he earned his master's degree. He served at St. Martin's Lutheran Church and School in Clintonville, WI, and as a teacher and principal at St. Paul's Lutheran School and Evansville Lutheran School. Victor was a faithful member of St. Paul's Lutheran Church where he was the organist and choir director.
In 1952 he married Darlene Ann Garling of Blairstown, Iowa, who had also been a student at Concordia, River Forest. Their marriage of 62 plus years was blessed with five children, all born in the space of five and a half years! Darlene had her hands full on Sunday mornings supervising all five children in the pew while Victor carried out his music ministry from the organ bench.
Victor is survived by his children, Mark Schuler (Rhoda), Paul Schuler (Pam), Sarah Scheidt (Dan), David Schuler (Carolyn), and Ann Courter (Terry); 9 grandchildren; and 12 great-grandchildren.
Victor was preceded in death by his wife, Darlene, in 2015; his parents; and a sister, Elsie Teske.
A service celebrating God's grace in the life of Victor will be held at 10:00 AM on Monday, December 3, 2018 at St. Paul's Lutheran Church, 100 East Michigan Street, Evansville, IN 47711. A private entombment will be held at Sunset Memorial Park Cemetery.
Friends may visit from 4:00 PM until 7:00 PM on Sunday, December 2, 2018 at Browning Funeral Home, 738 E. Diamond Ave., Evansville, IN 47711 and again from 9:00 AM until service time on Monday at the church.
Memorial contributions may be made to Evansville Lutheran School, 111 E. Virginia St., Evansville, IN 47711 or St. Paul's Lutheran Church.
Together Victor and Darlene are now celebrating the marriage feast of the Lamb in the heavenly Jerusalem as they await the resurrection pledged to them at their baptisms by the death and resurrection of their Savior, Jesus.
Condolences may be made online at www.browningfuneral.com.
Published in Courier Press on Dec. 1, 2018
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We are a team with a long experience in travelling around Ecuador, and especially in National Parks and Protected Reserves, we are to offer an improved and differentiated service to all tourists arriving in Ecuador. Our team is composed of some of the best authorized professional guides; some of them are English, German and French speaking. Our guides, together with our team of cooks, porters and office staff, are the key to make our clients´ trip an unforgettable lifetime experience.
Dracaena offers new routes to discover, for those people who really love travelling and are in search of something different, apart from the usual tourist programs.
Dracaena has been set up with a double objective: Answer our clients' needs in the best way possible. Our clients´ satisfaction is the most important for us. No matter the request, we have to be able to provide the best solution.
It is to offer a top class service at an accessible price, of course we are not the cheapest, but we are convinced that one pays for what one gets, and good service has definitely a moderate price.
Our ambition is NOT to operate a lot of groups, but to operate excellent quality groups. We believe that massive operation usually goes in detriment of a high quality in the operation. We are very aware of our capacity to operate in order to ensure the top service we aim at. Besides this, all our groups are small, since this aspect has shown proven satisfaction by our clients so far. Due to our tourist Reports help us enormously: our service is constantly evaluated, and the Tourist report survey is designed in such a way that identifies our strengths as well as our weaknesses very easily.
Our wish is to keep on growing at a controlled pace, being the trustful operator of more clients worldwide. We would like you to relax knowing that we are taking as much care of your clients as you would, since our objectives are the same: to give the best service available to your clients which are also ours. We are responsible because we know that our operation runs through the environment, culture and communities that are fragile and sensitive of being impacted.
Our goal is to be a real help to the local communities we work with, providing income and helping them to develop in a natural way, to provide positive cultural exchanges and operate in such a way that we not only try to maintain, but also improve the environment.


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Demonstrators crowd Broad Street in front of the Tennessee Aquarium during the Chattanooga Women's March on Saturday, Jan. 20, 2018, in Chattanooga, Tenn. Thousands of demonstrators gathered at Coolidge Park and marched across the Market Street Bridge through the city's tourist district to show solidarity with a national women's rights movement.
Thousands of women and supporters marched in Chattanooga Saturday afternoon in solidarity with a national movement supporting women's rights, speaking against sexual abuse and decrying the Trump administration on the anniversary of the president's inauguration.
"I am out here for my mother, for my daughter and for everyone who feels their rights are being stripped by this presidency," Monteagle resident Mary Clark, 61, said as she listened to speakers in Coolidge Park after the march.
Marchers gathered this weekend in hundreds of cities across the country and the world, as they tried to build on a movement that has only grown in its ambition.
The movement extended from last year's Women's March, when millions of women protested President Donald Trump's inauguration and advocated for women's rights and other issues.
A deluge of revelations about powerful men abusing women, leading to the #MeToo moment, has galvanized activists to demand deeper social and political change. And in the United States, progressive women are eager to translate their enthusiasm into electoral victories in this year's midterm elections.
Melody Shekari spoke on the topic at the Chattanooga event, urging attendees to be politically active. The former Congressional candidate warned of the low representation from women at the state and local level.
"It is time for us to make history here in southeast Tennessee," she said. "Women have not had an equal seat at the table. We need to vote and to volunteer, and we need to run for office to make that happen."
The local march was a least as big as last year's, which had an estimated 3,000 people, event organizers said.
"It has gone fantastically," event coordinator the Rev. Alaina Cobb said. "We have succeeded in elevating the voices of the real women of Chattanooga, who have experienced various forms of discrimination but refused to be silenced."
Marchers said they wanted to see policy changes while advocating for equal treatment for all, and the event brought a range of representation from people of all ages.
Local mother Amethyst Bogart was not able to come last year but brought her 3-month-old son Damien on Saturday.
"I wanted to see everyone come together and work together," she said. " Even though he's so young, I wanted him to be part of such a big movement in Chattanooga."
Across the region, thousands of people marched in Nashville, while more than 1,000 did the same in Memphis.
Chattanooga Mayor Andy Berke was encouraged by the "huge energy" animating the women's movement and said it showed that "women in Tennessee are really pushing for a new direction."
Jenny Sheridan Pecoraro of Nashville told The Tennessean that "the whole point is that you do something with this energy and this feeling." She said it gave those disappointed in the 2016 election results an outlet for their anger and a way to push for change.
President Donald Trump tweeted that it was a "perfect day" for women to march to celebrate the "economic success and wealth creation" that's happened during his first year in office — while women across the nation rallied against him and his policies.
"Get out there now to celebrate the historic milestones and unprecedented economic success and wealth creation that has taken place over the last 12 months," Trump wrote Saturday afternoon. "Lowest female unemployment in 18 years!"
But people participating in rallies and marches in the U.S. and around the world Saturday denounced Trump's views on immigration, abortion, LGBT rights, women's rights and more.
Mark Pace can be reached at 423-757-6659 or mpace@timesfreepress.com.
The Associated Press and New York Times News Service contributed to this report.


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Bipolar disorders and Wilson's disease
Mauro Giovanni Carta1,
Orazio Sorbello1,
Maria Francesca Moro1,
Krishna M Bhat2,
Enrico Demelia1,
Alessandra Serra1,
Gioia Mura1,
Federica Sancassiani1,
Mario Piga1 &
Luigi Demelia1
BMC Psychiatry volume 12, Article number: 52 (2012) Cite this article
The aim of this study was to determine the risk for Bipolar Disorder (BD) in Wilson's disease (WD) and to measure the impaired Quality of Life (QL) in BD with WD using standardized psychiatric diagnostic tools and a case control design.
This was a case control study. The cases were 23 consecutive patients with WD treated at the University Hospital in Cagliari, Italy, and the controls were 92 sex- and age-matched subjects with no diagnosis of WD who were randomly selected from a database used previously for an epidemiological study. Psychiatric diagnoses according to DSM-IV criteria were determined by physicians using structured interview tools (ANTAS-SCID). QL was measured by means of SF-12.
Compared to controls, WD patients had lower scores on the SF-12 and higher lifetime prevalence of DSM-IV major depressive disorders (OR = 5.7, 95% CI 2.4–17.3) and bipolar disorders (OR = 12.9, 95% CI 3.6–46.3). BD was associated with lower SF-12 in WD patients.
This study was the first to show an association between BD and WD using standardized diagnostic tools and a case control design. Reports in the literature about increased schizophrenia-like psychosis in WD and a lack of association with bipolar disorders may thus have been based on a more inclusive diagnosis of schizophrenia in the past. Our findings may explain the frequent reports of loss of emotional control, hyperactivity, loss of sexual inhibition, and irritability in WD patients. This study was limited by a small sample size.
Wilson's disease (WD) is an inherited autosomal recessive disorder that affects copper metabolism. It is caused by mutations in a gene on chromosome 13 that encodes ATP 7B, an adenosine triphosphatase involved in copper transportation across cell membranes [1, 2]. The prevalence of WD is approximately 1:30,000, with a carrier prevalence of 1:90 [3]. Prompt diagnosis and treatment is critical; the disease is fatal unless treated, and effective treatment is available [4]. The clinical manifestations of WD result from gradual accumulation of free copper in tissues, which can damage many organs. Most WD patients have signs of liver and central nervous system involvement. WD at presentation can have diverse clinical features, including hepatic, neurological, and psychiatric manifestations. WD is usually diagnosed in patients between 6 and 8 years of age when symptoms first become clear [5]. Onset in patients >40 years is rare [6].
The psychiatric manifestations of WD have been reported frequently since the original paper by S.A.K Wilson was published in 1912 [7]. In his report, Wilson describes psychiatric symptoms in 8 of 12 cases, and "schizophrenia-like psychosis" in 2 of the cases. Other reports describe a wide spectrum of psychiatric disorders, including cognitive impairment [8], dementia [9], mental retardation [10], anxiety [11], "schizophrenia-like states" [12], and behavior abnormalities and personality disorders [13].
Depression is extremely common in WD patients, affecting 30–60% of those with WD [13, 14]. An association between the degree of disability and the presence of depression has not been established, however. Furthermore, the prevalence of depression is higher in WD than in other chronic disabling diseases, such as rheumatic arthritis, even when there is a similar level of disability [15].
Other mood disorders, such as hypomania and frank mania have also been reported in WD in recent years in two large case series [16, 17] and there is some evidence of bipolar disorder in WD in descriptions of two cases in which a manic episode preceded the onset of neurological symptoms [18, 19].
Costa-Machado and colleagues [18] suggested that there may be a higher association between bipolar disorder and WD than has been reported in literature.
A study confirming the case series evidence with using standardized diagnostic criteria and a matched case controls methodology will be of interest in terms of clinical practice, and probably in accordance with the broadening of the concept of bipolar disorder in present day psychiatry [20]. Indeed, recent studies indicate that higher levels of copper, similar to several other trace elements such as zinc, cadmium, and thallium, may play a role in the pathophysiology of bipolar disorder, which is consistent with the neurodegenerative hypothesis of such a disorders [21].
The objectives of this study were to determine the frequency of bipolar disorders and mood disorders in a consecutive series of WD inpatients using standardized diagnostic tools and to compare the risk for bipolar disorder in WD patients with the risk in controls. Data were collected from the controls for use in a large epidemiological study [22, 23].
The subjective perception of quality of life is a construct that is very relevant to measures of outcomes in chronic disease [24, 25], particularly in patients with diseases that impact heavily the daily life of the affected patients and their families [26], such as WD. Thus, the secondary objective of this study was to evaluate the impairment of quality of life and the relationship between mood disorders and impaired quality of life in WD.
This was a case control study.
The cases were 23 consecutive WD patients seen between January and September 2010 at the Gastroenterology Unit at the University Hospital in Cagliari, Italy, a center of excellence that cares WD patients from all regions in Italy. The controls included 92 subjects with no diagnosis of WD who were randomly selected from a database used for an epidemiological study of health conditions in Italy [22, 23]. The selection of sex- age-and residence matched controls from the 3498-subject database from six Italian regions (2 from the North, 1 from the Center, 2 from the South plus Sardinia) was performed using a randomized block design. A block was constructed for each case that included all eligible age-matched (± 1 year),sex-matched and residence-matched (North 1 Case 4.3%, South 1 Case 4.3%, Center 0% Italy and Sardinia 21 Cases = 82.6%) controls in the database. Four individuals per block were extracted for each case, automatically excluding them from remaining blocks.
Psychiatric diagnosis interview, tools, and psychiatric assessment
The psychiatric interviews were conducted using several standardized tools. First, we used a standard form to record basic demographic data. Second, the "Advanced Neuropsychiatric Tools and Assessment Schedule" (ANTAS) [22], a semi-structured clinical interview derived in part from the non-patient version (SCIDI/NP) for DSM-IV [27] (First et al. 2001), was used to assess the presence of full or sub-threshold psychiatric disorders. The ANTAS tool was administered by physicians, which was necessary for it to be administered according to the study protocol. A preliminary reliability study of the diagnoses derived from ANTAS and SCID was carried out, and the results were published previously. The reliability in terms of mood and anxiety diagnoses using ANTAS vs. SCID was measured, and the mean K was 0.85 [20]. Third, the Mood Disorder Questionnaire (MDQ; Italian version) [28] was used to assess bipolar spectrum disorders. The adopted MDQ cut off was 7 (Bipolar Cases identified by score of 7 or more) [28].
Fourth, quality of life was evaluated with the Short Form Health Survey (SF-12) [29]. The SF-12 includes the following dimensions: physical activity, physical health limitations on roles or activities, emotional state, physical pain, self-evaluation of general state of health, vitality, social activity, and mental health. The period of measurement was the month prior to evaluation. Higher scores on the SF-12 correspond to better conditions and quality of life. Finally, the interviewers asked the interviewees to show them the packages of drugs they used and then retained all of the psychotropic drug box covers in a folder provided for this purpose.
Diagnosis of WD
The diagnosis for each WD patient was made by evaluating the clinical symptoms, laboratory test results, and results of mutation analysis [30]. Confirmation of the clinical diagnosis included decreased serum ceruloplasmin concentration, high serum non-ceruloplasmin-bound copper concentration, low serum copper concentration, elevated 24-h urinary copper excretion, elevated hepatic copper content (>250 μg/g dry weight), the presence of Kayser-Fleischer rings by slit lamp examination, and ATP7B mutation.
Liver function tests were performed, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and g-glutamyl transpeptidase (GGT) tests. Quantitative determination of serum ceruloplasmin concentrations was performed using automated clinical chemistry analyzers (Array Protein System 360, Beckman Instruments, California, USA) using a nephelometric assay. The reference range for serum ceruloplasmin is between 200–600 mg/liter. Serum copper and urinary copper concentrations were measured using an inductively coupled plasma optical emission spectrometer. The reference range for serum copper is 10–22 μmol/liter. In WD, the urinary copper output is >1.5 μmoles/24 h. Liver copper concentration in dried liver tissue was measured by flame atomic absorption spectroscopy (Instrumentation Laboratory Video 22). Liver copper content >250 μg/g dry weight is diagnostic for WD.
Screening controls for WD
During the interviews of the controls, each was asked about general well being, the presence of illness, consultation with physicians, and medical tests they underwent both routinely (e.g., work or driver license eligibility tests) or to help diagnose or monitor medical issues. Diagnosis of physical illness was reported using a structured form.
Lifetime prevalence for DSM-IV major depressive disorder, bipolar disorder, panic disorder, and "at least a diagnosis of anxiety by DSM-IV" was calculated for the case and control groups, as was lifetime positivity (a score >12) on the MDQ as an indicator of bipolar spectrum disorder. The odds ratio association (univariate analysis) for DSM-IV diagnosis (dependent variable) was calculated using the control group as "pivot". Statistical significance was calculated using the χ 2 test in 2 × 2 tables. Odds ratio 95% confidence intervals (OR 95% CI) were calculated using the method of Miettinen [31]. The comparisons between the scores at SF-12 in the study groups were calculated using the ANOVA one-way statistic, in alternative, particularly when the size of the samples did not allow the use of parametric test, the U Mann Whitney test was used.
Each study subject provided informed consent for the use of anonymous data for an aggregate study. The community study (involving the controls) was approved by the ethics committee of the Italian National Health Institute (Rome), and the present study was approved by the ethics committee at the Università Europea del Mediterraneo ONLUS. Data were not nominal at the source, and each subject was identified with a code number.
The demographic characteristics of the study subjects are shown in Table 1. Age and sex were homogeneous in cases and controls due to the matching method. The mean time on illness for WD patients was about 12 years. Patients with WD had lower SF-12 scores than controls (Table 2), a higher lifetime prevalence of manic/hypomanic episodes (with positivity as assessed on the MDQ), and a higher prevalence of lifetime DSM-IV major depressive disorders and bipolar disorders as detected by the ANTAS interview. The differences between cases and controls in terms of the frequency of panic disorders and total anxiety disorders were notable but not statistically significant: 8.7% vs. 5.4% for panic disorders, and 17.3% vs. 6.5% for all anxiety disorders in cases and controls, respectively.
Table 1 Demographic Data and SPECT positivity in the sample
Table 2 Lifetime Prevalence of Psychiatric Disorders and Quality of Life in Cases and Controls
Table 3 compares Subjective Quality of Life (measured as SF-12 score) in WD patients with Bipolar Disorders (N = 7) – column left; and MDD (N = 11) column right; WD with Bipolar Disorder patients had SF-12 mean score worse than WD patients without Bipolar Disorders (N = 16, 11 of which had MDD) [F (1,21,22 df) = 4.75, P = 0.041 ANOVA 1 way]; had a worse mean SF-12 of WD patients without MDD or Bipolar diagnosis (23WD – 11 (MDD) – 7 (BD) = 5 cases) but the difference not reach the statistically significance [U = 8, Z = -1,54, P = 0.159, using Mann-Withney test due to the not applicability of parametric test]; had SF-12 mean score worse than WD patients with MDD (N = 11), [F(1,16,17) =3.31, P = 0.087, Anova 1 way]. WD with MDD patients had SF-12 mean score higher than WD patients without MDD (N = 12, 7 of which had BD), but without any statistically significance [F(1,21,22) = 0.43, P = 0.519, ANOVA 1 way]; had a worse mean SF-12 of WD patients without MDD or Bipolar diagnosis (23WD – 11 (MDD) – 7 (BD) = 5 cases) but the difference not reach the statistically significance [U = 24,Z = -0,40, P = 0.74, using Mann-Withney test due to the not applicability of parametric test];
Table 3 Quality of Life (SF-12 mean ± standard deviation score) and Mood Disorders in Wilson's Diseases Patients
This study is the first to use a standardized epidemiological case–control design and standardized diagnostic tools (DSM-IV SCID-ANTAS) for studying the association between mood disorders and WD. The results indicated that the lifetime prevalence of DSM-IV bipolar and major depressive disorders is higher in people with WD than in sex- and age-matched controls. The OR was 12.9 for bipolar disorders and 6.7 for major depressive disorders. Notably, there was a difference in prevalence even though (due the random hazard method) the randomized control sample had a particularly high prevalence of bipolar and major depressive disorders than the population from which it was drawn [22]. For example, MDQ positivity was 3.0% in the database population, but 9.8% in the random control sample. These differences were in part due to the fact that MDQ frequencies are highly influenced by sex, age and, in particular residency, and a high frequency in the control group is likely because of these variables. While the controls had a higher prevalence of MDQ (and BP detected by SCID-ANTAS thus, with another method) than in the population from which it was extracted, cases of WD had higher prevalence of MDQ + and BP-DSMIV at statistically significant level than the controls.
According to the algorithm of DSM-IV MDD diagnosis excludes BP and vice versa, and 11 (47.8%) cases had MDD and 7 (30.4%) had BD. The percentage of cases with depressive disorder is in the same range as previous studies cited in the introduction (30–60% for depression as noted in the review of Akil and Brewer [13]). In general, the previous case series showed about 60–80% of comorbidity between WD and psychiatric disorders [17], similar to our data considering that out of 4 cases of Anxiety Disorders, 1 had co-morbidity with MDD and 2 had comorbidity with PD, and only 1 was independent of the mood disorder. Thus, the total psychiatric cases were 19 (82.6%).
The association with bipolar spectrum disorders was confirmed using this more inclusive method, i.e. the MDQ questionnaire, which is capable of including a wider spectrum of bipolar disorders in the "positives" compared to the DSM-IV criteria. The reliability of the diagnosis of Bipolar Disorder using structured tools and the clinical judgment in a clinic is in fact controversial, with some researchers viewing them as reliable [32, 33] and others considering them as not reliable [20, 34].
Our study shows an association between Bipolar Disorder and WD using the strict algorithm of DSM-IV or using the more comprehensive "spectrum" subject detected by MDQ.
Our study showed an association between bipolar disorders and lower quality of life as measured using SF-12. However, the design of the study did not allow us to clarify whether the bipolarity caused the lower quality of life or whether this was a confounding factor due to another factor (as cerebral damage) causing both bipolarity and lower quality of life.
The strong association between bipolar disorders and WD should be interpreted, keeping in mind the modification of the diagnostic criteria and the evolution of the concept of "Bipolar Spectrum Disorders" in the last few decades [35]. It seems likely that literature reports in the past of "schizophrenia-like psychosis" in WD were due to use of a different definition of schizophrenia compared to current psychiatric diagnostic criteria. In contrast, the association of WD and bipolar disorder may explain the frequent descriptions of "loss of emotional control, hyperactivity, or loss of sexual inhibition, irritability" reported in WD patients [4, 16]. A high risk of bipolar disorders in WD may also be related to the higher incidence of suicidal behavior, which is present in 4% to 16% of patients with WD across studies [13, 36].
Machado and colleagues [16] suggested that there was a higher association between bipolar disorder and WD than has been reported in the literature. In their case series, which describes the neurological manifestations of 119 patients with WD, the authors observed the psychiatric disorders catatonia, agitation, aggression, delusional thoughts, and mania. The same group, noting that there are few reports in the literature of WD patients with typical bipolar affective disorder [18], described a patient with WD whose initial manifestation was a manic episode followed by depression. Tremors in the upper limbs appeared one year after the onset of symptoms. The diagnosis of WD was established three years after the first symptoms appeared, based on the neuropsychiatric picture, detection of Kayser-Fleischer rings, and the results of diagnostic tests that indicated chronic liver disease and excess copper. Another case of mania as the first manifestation of WD was described earlier by Kumar Chand et al. [19] in an 18-year-old boy who presented to a psychiatric clinic with manic syndrome and a high propensity for extrapyramidal symptoms due to a neuroleptic. The author concluded that psychiatrists need to recognize that WD can rarely present as an isolated psychiatric symptom, including mania. Thus, early and severe extrapyramidal symptoms secondary to neuroleptic exposure in an adolescent warrant a detailed evaluation to rule out underlying neuropsychiatric conditions. Our results, which underline the strong association between bipolar disorder and WD, support this idea.
It is interesting to consider these results in light of the pathogenic hypothesis.
Early studies showed that women affected by chronic depression sometimes have copper, zinc, and cesium deficiencies [37, 38]. Later studies suggest that the presence of depression and other neuropsychiatric symptoms is due to the deposit of copper in the central nervous system [39]. Eggers et al. [40] used SPECT to demonstrate a reduction in thalamic-hypothalamic presynaptic dopamine and serotonin transporters due to the accumulation of copper. There was a negative correlation between the density of presynaptic dopamine transporters and the severity of depression as assessed using the Hamilton Rating Scale for Depression.
It was recently hypothesized that trace elements play an important role in the pathogenesis of bipolar disorders by causing neurodegeneration [41]. Moreover, essential elements like vanadium have been implicated as a causative factor for bipolar mood disorder, while elevated vanadium and molybdenum levels have been reported in serum samples from bipolar mood disorder patients [41]. This latter study showed, using DSM-IV standard diagnostic criteria and classification into types I, II, and V according to the concept of Young and Klerman, that Na, K, P, Cu, Al, and Mn were elevated significantly in Bipolar I (Mania) (P < 0.001). In Bipolar II hypomania, Na, S, Al, and Mn were increased significantly (P < 0.02), while in Bipolar II depression, Na, K, Cu, and Al were increased significantly (P < 0.001). Finally, in Bipolar V, Na, Mg, P, Cu, and Al were increased significantly (P < 0.002) compared to a control group [41]. A recent study by Gonzales-Estecha and colleagues [21] found higher serum copper and zinc, blood lead and cadmium, and urine lead, cadmium, and thallium concentrations in patients diagnosed with bipolar disorders compared to a control group.
Increased neuronal oxidative stress (OxS) induces deleterious effects on signal transduction, structural plasticity and cellular resilience, mostly by inducing lipid peroxidation in membranes, proteins and genes [42]. It has been hypothesized that these pathological processes occur in critical brain circuits that regulate affective functioning, emotions, motoric behavior and pleasure involved in bipolar disorder (BD) [43, 44].
The brain is particularly vulnerable to oxidative damage since it contains large amounts of polysaturated fatty acids and possesses low antioxidant capacity [45]. Several studies have demonstrated altered OxS parameters in the pathophysiology and therapeutics of BD, including changes in the levels of enzymes superoxide dismutase (SOD), catalase (CAT) and thiobarbituric acid reactive substances (TBARS) [46]. The well-known stabilizing agent Lithium was found to limit the enzyme activity, potentially lowering hydrogen peroxide and hydroxyl radical formation. Similarly, lithium was also shown to reverse increased OxS parameters in BD [43, 47]. For instance, a decline in lipid peroxidation and an increase in CAT levels were observed in valproate and lithium-treated rats [42, 48]. Accumulation of copper was shown to increase oxidative stress in bivalve species [49]. In skeletal muscle of Broilers Under Heat Stress, copper decreases because of dietary Selenium, Vitamin E, and their combination with an increase in antioxidant defense [50]. In humans accumulation of copper was associated with oxidative stress in allergic asthma patients, and introduction of nutritional supplement therapy accompanies improved oxidative stress, immune response, pulmonary function, and decrease in copper plasma levels [51]. On the other hands copper levels were elevated in several brain areas in a degenerative disease such as Niemann-Pick C [52]. Interestingly, Nieman-Pick C disease was specifically indicated to be associated with Bipolar Disorders [53]. If the results of our study are further confirmed, it will lend significant support to the hypothesis that minerals such as copper play an etiological role in psychiatric disorders, and WD may serve as a pathogenic model for the bipolar disorder.
This study was limited by its small sample size. Further research is warranted to confirm the results and the role that neurological lesions play in the pathogenesis of bipolar disorders. In addition, the link between neurological lesions, bipolar disorders, and low level of quality of life in WD awaits further clarification.
In agreement with the literature [11], this study indicated a high risk for panic disorder (OR = 1.7) and for anxiety disorders as a whole (OR = 4.5) in WD, although there was no statistically significant difference between cases and controls. The finding that WD patients did not have an increased risk of anxiety disorders must be interpreted with caution since the power of the study was insufficient in terms of revealing low-level risk.
In this study, the diagnosis of WD in the cases was made using standardized tools and clinical and laboratories assays. In contrast, the data bank used for extraction of control data reported a WD diagnosis only on the basis of the anamnesis of the subject in the 'general health' section of the questionnaire. Thus, there may be a slight risk of false negatives in the group of controls, although this risk was very low due to the rarity of WD in the community (1:30,000; thus the probability of a control subject not reporting WD would be 30,000/92). Even if there was a false negative among the control subjects, this would reinforce the null hypothesis of no increased risk for mood disorders in WD. This limitation therefore does not invalidate the results of the study.
In general, reliability and validity of diagnosis of Bipolar Disorders using standardized tools (as ANTAS-SCID) and self-administered questionnaire (as MDQ) [18], may be problematic, however, this is a general limitation of the epidemiological research in psychiatry more than a specific limit of this study. We have tried to address this limitation, at least partially, by using a clinician for the interview and a semi-structured tool as opposed to a medically lay person with rigid and structured interview and by using both methodologies (interviews and self-reporting tools).
This study may have inducted a Berskon's Bias due to the case control design, on the other hand, the study was carried out in a general hospital setting without a psychiatric ward, therefore this risk is relatively low.
This study was the first to show an association between BD and WD using standardized diagnostic tools and a case control design. Reports in the literature about increased schizophrenia-like psychosis in WD and a lack of association with bipolar disorders may thus have been based on a more inclusive diagnosis of schizophrenia in the past. Our findings may explain the frequent reports of loss of emotional control, hyperactivity, loss of sexual inhibition, and irritability in WD patients.
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The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-244X/12/52/prepub
University of Cagliari, Italy, Cagliari, Italy
Mauro Giovanni Carta, Orazio Sorbello, Maria Francesca Moro, Enrico Demelia, Alessandra Serra, Gioia Mura, Federica Sancassiani, Mario Piga & Luigi Demelia
Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, TX, USA
Krishna M Bhat
Mauro Giovanni Carta
Orazio Sorbello
Maria Francesca Moro
Enrico Demelia
Alessandra Serra
Gioia Mura
Federica Sancassiani
Mario Piga
Luigi Demelia
Correspondence to Mauro Giovanni Carta.
MGC participated in the design and coordination of the study, in the acquisition and analysis of the data and drafted the manuscript. MP participated in the analysis of the data and drafted the manuscript. LD participated in the design and coordination of the study and critical revision of the manuscript. KMB participated in the analysis of the data and drafted the manuscript. MFM, OS, ED, AS, GM, FS participated in the design of the study, in the acquisition and analysis of the data and drafted the manuscript. All authors read and approved the final manuscript.
Carta, M.G., Sorbello, O., Moro, M.F. et al. Bipolar disorders and Wilson's disease. BMC Psychiatry 12, 52 (2012). https://doi.org/10.1186/1471-244X-12-52
DOI: https://doi.org/10.1186/1471-244X-12-52
Serum Copper
Case Control Design


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Simon Jones has a rich background with the guitar, which has come full circle with his role with the Yamaha Guitar Group. As a teenager he played, and even built his own guitar to play with his friends. He continued to play in college and took an interesting path within the pro audio and recording fields first by working for EMI, taking him to experience the mobile studio in Norway and jobs at Abbey Road Studios in London. For a time Simon worked closely with David Martin, the founder of Martin Audio, on sound reinforcement technology and helped launch the first company's club speakers.  In 1995 Simon was hired by JBL and later worked with the TC Group, RKS Guitars and Line 6. When Yamaha purchased Line 6 in 2014, Simon focused on marketing of the guitar gear, which would later include the Ampeg line as well as the Yamaha guitar line. He proudly oversees many projects near and dear to his passion for the guitar and enjoys the team he is a part of.
Yamaha Guitar Group
British Music Industry
Music Manufacturing
If you have updated information, contact or demographic details on this person, please contact Dan Del Fiorentino
Find out more about NAMM!


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Philadelphia Funds Digital Literacy to Prep for the Census
With the 2020 Census deadline growing closer, the city will use its digital inclusion grant-making program to educate citizens about the importance of being counted, and to help train census workers.
by Zack Quaintance / May 23, 2019
Philadelphia City Hall Shutterstock/Marco Rubino
Philadelphia's Digital Literacy Alliance — a coalition that works to ensure city residents have access to technology and the skills to use it — will focus its annual grant-making on the upcoming 2020 U.S. Census.
This mark's the Alliance's third round of grant making, having previously given out a total of $350,000 — generally between $10,000 and $25,000 — to community groups, schools and others who work toward digital equity. According to Andrew Buss, Philadelphia's deputy CIO for innovation management, a change made this year will concentrate efforts on the forthcoming census.
In coming months, the city will give roughly $200,000 to push digital literacy and help with census counting. Examples include: educating citizens on why they should get counted, or preparing census workers for the unique challenges of 2020, which marks the nation's first digital census. The grants will be between $10,000 and $25,000 for single applicants, with up to $40,000 available for collaborative efforts. The city will spend the next couple of months soliciting proposals, with the first recipients to be announced in August.
SXSW 2019: Local Gov Data Scientists Vital for 2020 Census2020 Census Process to Lean Heavily on Smartphone TechDetroit Counts on Tech to Prep for the 2020 Census
Linking digital literacy and census preparation makes sense since this is the nation's first digital collection of information about its population. But there are other reasons too. Statistically, the percentage of people Philadelphia estimates went uncounted in the 2010 Census is roughly equivalent to the number of its residents who don't have high-speed Internet connections at home, said Stephanie Reid, who is leading the city's census work as the executive director of Philly Counts 2020.
That doesn't mean that it's the same people, however. Reid noted that a key factor in a successful count is understanding the unique qualities of communities, and in that context, those numbers are important to think about.
Organizers aren't entirely sure which projects — and their organizations — to back with the grants. Both Reid and Buss said that receiving creative ideas that hadn't yet occurred to the city would be an ideal scenario. One thing Philadephia will be looking for is census-related digital literacy projects that have the potential to continue developing the city's digital inclusion infrastructure — now roughly eight years in the making — after the census has ended. This could, for example, take the form of a new public computer lab aimed at helping census workers complete digital training that would transition into helping community members learn computing skills they could use to boost their employment prospects.
"It would be a real shame to have all these resources for a year and a half, but when the census is over, everything goes away," said Reid.
The census is always an important undertaking that can impact both how many congressional seats a given region has and how much funding it gets from the federal government. Philadelphia, for example, receives $3.3 billion from the federal government, all of which is dependent on the census. A substantial undercounting could cost the city vital money for crucial tasks like repairing roads.
One area of concern this year is training census workers. According to Reid, these workers need to be intimately familiar with the communities they are working to count; they need to know the culture, the vernacular, and the other little things that someone from elsewhere cannot. In order to work with this first digital census, individuals must complete 14 hours of webinar training on their own, all of which must be done on a computer, rather than a tablet or phone.
This can be a major challenge in neighborhoods with a low percentage of residents who have access to broadband at home. To that end, Philadelphia is currently identifying computer labs in neighborhoods that people can use.
These are just some of the challenges Philadelphia faces. The city must keep things local while adhering to federal requirements, all with substantially less funding than they had in 2010. Tech can be a blessing when it comes to counting more Internet-savvy residents, but also a challenge for those on the wrong side of the digital divide.
More information about applying for the Digital Literacy Alliance's new round of grants can be found on its website.
SXSW 2019: Local Gov Data Scientists Vital for 2020 Census
2020 Census Process to Lean Heavily on Smartphone Tech
Detroit Counts on Tech to Prep for the 2020 Census


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ProjectsAnne D Pham2022-10-03T01:02:32+00:00
ALSFAC has contributed to major scientific progress in our understanding of the underlying biology behind ALS. As a direct result of the funded projects, research teams helped develop over 130 pre-clinical models and collect more than 4,440 patient medical records, and more than 8,300 samples. They also have helped identify 2 new ALS genes and validate one new ALS imaging biomarker.
Answer ALS
Principal Investigator(s):
Jeff Rothstein
Merit Cudkowicz
Clive Svendsen
Collaborators involved: Leslie Thompson, PhD, Steve Finkbeiner, MD/PhD, Ernest Fraenkel, PhD, Jenny van Eyk, PhD
Overview and description:
The Answer ALS project has four components:
To collect 1000 ALS patient's clinical data and biosamples
a) Including biofluids, tissue, blood, autopsy, DNA, PBMC's, and
b) Digital data from smart phone-based applications
To generate stem cells from every patient
To use these stem cells to perform comprehensive biological analytics (generating extensive data on each patient)
To analyze these data and make the data widely available to the community
The ultimate goal of the Answer ALS initiative is to be able to identify distinct disease subpopulations to better enable future precision medicine approaches and designer drugs.
Funding: ALSFAC, Packard Center, the ALS Association, and others
Web site: Answer ALS – Answer ALS
Publications related to Answer ALS: Answer ALS | Data Portal
Bloom/DiAntonio submission (Washington University in St. Louis):
Aaron DiAntonio, MD, PhD, Developmental Biology
Joseph Bloom, Assistant Professor of Genetics and Assistant Director of the Needleman Center for Neurometabolism and Axonal Therapeutics
Jeffrey Milbrandt, MD, PhD
Coleman/Sreedharan submission (Cambridge University/Kings College London):
Michael Coleman, PhD, University of Cambridge
Jemeen Sreedharan, MBBS, MRCP, PhD
Freeman lab submission (Vollum Institute, Oregon Health Sciences):
Marc Freeman, PhD, Director and Senior Scientist at OHSU's Vollum Institute
Lagier-Tourenne/Ward submission (Harvard/NIH)
Clotilde Lagier-Tourenne, MD, PhD, Associate Professor of Neurology at Massachusetts General Hospital and Harvard Medical School
Michael Ward, MD, PhD, National Institutes of Health
Arrest ALS – In collaboration with the ALS Association, we are pleased to announce the recent funding of four new grants designed to elucidate the biological linkages between key drivers of active axonal degeneration and ALS. ALS Finding a Cure® and the ALS Association are pleased to further scientific advances in this important area of research, which are sure to lead to future therapeutic insights. The four projects funded through the Arrest ALS collaboration include:
Bloom/DiAntonio submission (Washington University in St. Louis)
Coleman/Sreedharan submission (Cambridge University/Kings College London)
Freeman lab submission (Vollum Institute, Oregon Health Sciences)
Funding: ALS Finding a Cure and Leandro P. Rizzuto Foundation
Website: Arrest ALS
Developing a Novel TDP43 PET Agent (Co-Funded ALSFAC and the ALS Association)
Yuna Ayala
Nigel Cairns
Paul Kotzbauer
TDP43 is the dominant neuropathology in ALS, found in 97% of brains studied during autopsies. This project, the winner of a $1M Challenge collaboratively funded by the ALS Association and ALSFAC, is focused on developing a PET imaging agent that binds selectively to abnormally aggregated TDP43, for use in imaging patients with suspected or diagnosed ALS. Such an imaging agent would be a powerful tool for use in both ALS clinical trials, as well as diagnosis.
Funding: ALSFAC, the ALS Association, and the Association for Frontotemporal Degeneration
Accelerating the Identification of Gene Suppressors (Brown University, UMass, MGH)
Bob Brown, MD/DPhl
Justin Fallon, PhD
Anne Hart, PhD,
Diane Lipscombe, PhD
Robert Reenan, PhD
Brian Wainger, MD/PhD
Kristi Wharton, PhD
Brown University, University of Massachusetts and Massachusetts General Hospital
The goal of the Accelerating ID Project is to identify the earliest detectable disease changes and to look for genes with the ability to suppress disease changes across 4 different animal and human-based models of ALS. This collaboration across 7 laboratories is specifically focused on:
Using unbiased screens to look for disease suppressors in worm and fly models of ALS
Performing sensitive new behavioral analyses in mice to detect early and subtle changes,
Exploring abnormal firing patterns in human stem cell-derived motor neurons from different genetic backgrounds
Disseminating the novel research tools that have been generated through the project
The labs have been generating novel genetic ALS models in flies and worms in order to look for disease suppressors across both models, and are now beginning to assess these suppressors in mouse and human-derived stem cells in hopes of identifying novel drug targets.
Web site: Brown.edu
ALERT (ALS Early Recognition Timeline) Project
Katherine Nicholson MD
Nazem Atassi MD
People with ALS often seek evaluation from multiple providers prior to diagnosis, with an average time from symptom onset to diagnosis of 11.5 months. The goal of this study is to accelerate ALS diagnosis by developing a natural language processing-based algorithm to identify people at risk for ALS and a scale to help physicians identify people with ALS at early stages of the disease. We aim to scale up these early ALS diagnostic tools for use in many US hospitals, with the ultimate goal to identify and treat people with ALS early in the disease when chances of drug success are higher. This project is co-funded by ALS Finding a Cure and Biogen.
Application of MultiOmyx to iPSC Models of ALS
Clive Svendsen PhD
Induced pluripotent stem cell technology (iPSC) holds great promise for accelerating our understanding of the molecular mechanisms and pathways leading to motor neuron degeneration in ALS. In vitro cellular model systems generated from patient-derived iPSC lines can recapitulate many aspects of in vivo cellular pathology, and beyond basic disease research may serve as a powerful test bed to screen potential therapies. Therapeutic screening on iPSC-derived models will likely be complementary to, and in some aspects superior to other approaches, including animal models in terms of human-predictivity and speed. GE developed a unique technology platform allowing the in vitro analysis of cells and tissues to an extent not previously possible (MultiOmyx, or "MO"). An iterative labeling process allows repeated immunocytochemical visualization of 60 or more protein markers in a single sample, as well as RNA and DNA. Precision hardware and custom software for imaging and analytics enable extensive characterization of single cell structure and function as well as relationships with neighboring cells and environment. Application of this technology to ALS iPSC systems is likely to advance the utility of these models and provide new insights into neurodegenerative pathways and mechanisms.
AT HOME Study (Barrows Neurological Institute and Beth Israel Deaconess Medical Center )
Jeremy Shefner MD, Barrow Neurological Institute
Seward Rutkove, Harvard Medical School
Jeremy Shefner, Deaconess Medical Center
Collaborators involved: Barrows Neurological Institute, Beth Israel Deaconess Medical Center
Only a small percentage of patients with ALS participate in clinical trials. A major reason is that trials are conducted in a limited number of academic medical centers, and that in-person visits are required on a frequent basis. At these visits, trial outcome measures are obtained, with trained evaluators performing these measures. Our study will test the hypothesis that ALS patients can perform clinically meaningful outcome assessments at home, thus obviating a major need to come to the study center. We will provide simple tools for assessment, train subjects via webinars, and patients will enter their data to an online portal. For a sample of participating patients, we will compare AT HOME measures with those obtained at regular study visits by trained evaluators. We will also assess the extent to which frequent sampling of measures can reduce the variability of measurement; we expect that such sampling will increase reliability of measurement and potentially reduce the sample size required to see meaningful changes in response to experimental therapies.
Web site: ClinicalTrials.gov, Northeast Amyotrophic Lateral Sclerosis Consortium (NEALS)
Combined Stem Cell and Gene Therapy
Gretchen Thomsen (Cedars Sinai)
This study combined two exciting new areas in clinical development: Stem Cells and Gene therapy. Stem cells have the ability to divide and adapt to new environments. This project took advantage of these capabilities to transplant brain support cells that were genetically modified to express the growth factor GDNF. ALSFAC funded initial studies testing this approach in animals and the investigators then advanced to transplanting these cells into the spinal cords of ALS patients to assess their safety and whether they could promote any benefit/stabilization of disease.
Web site: https://www.cedars-sinai.org/newsroom/cedars-sinai-awarded-1199-million-for-als-clinical-trial/
Presymptomatic Biomarkers in Dominantly Inherited ALS (DIALS)
Katharine Nicholson, MD
Tim Miller, MD/PhD
James Berry, MD
Collaborators involved: Massachusetts General Hospital and Washington University
DIALS was a multi-center initiative to follow pre-symptomatic ALS mutant gene carriers longitudinally in order to identify biomarkers at (or as close as possible to) the point of conversion to disease. The study not only used traditional clinical assessments, but also incorporated the novel strength measures ATLIS (measure of upper and lower limb strength) and the Iowa Oral Performance Instrument (IOPI) (a measurement of bulbar muscle strength) as well as the assessment of several potential fluid-based biomarkers. This project was originally funded to enroll 20 patients, but received additional funding from Target ALS to add another 40 patients, and Biogen to add an addition 25 patients.
Imaging Axonal Transport
Robert Brown D.Phil., MD
Collaborators involved:
Merit Cudkowicz MD, Massachusetts General Hospital
Clive Svendsen PhD, Cedars-Sinai Regenerative Medicine Institute
Robert Brown D.Phil., MD, University of Massachusetts Medical School
The field of ALS needs a tool, often called a biomarker, by which the activity of this disease can be gauged. This is potentially important not only for diagnosing the disease, but also for identifying factors causing ALS and for gauging the efficacy of putative ALS treatments. One such biomarker is to quantify a parameter that directly reflects the health of the motor neuron. One property that is promising in this regard is axonal transport, the process by which a nerve cell moves cargoes such as proteins and organelles up and down its long processes known as axons. It is clear in ALS mice that as ALS progresses, axonal transport fails. There is no way yet to quantify rates of axonal transport in living mammals. The goal of this project is to use a non-toxic fragment of tetanus toxin to record rates of axonal transport in human motor nerves. Our group has long-standing experience studying this fragment of tetanus (called TTC) for this purpose. In the present study, we will test ways to label TTC so that we can visualize and quantify its movement using either MRI scans or a method called PET scanning.
Impact of Study
We believe this study can potentially have a high impact. This is in part because of the urgent need for a quantitative biomarker in ALS. It is also because a measure of axonal transport should be useful in many other disorders of the motor nerve, including motor neuropathies, some types of muscular dystrophy, and traumatic nerve injury.
Common Goals
Finding a common biomarker is a goal shared by many ALS investigators, including others in the ALS Finding A Cure Foundation. In this regard, our work dovetails well with the studies in this consortium using PET ligands to visual neuroinflammation. Moreover, these biomarkers should prove useful in gauging success of any ALS treatment trials that emerge from this consortium.
Microbiome in ALS (MGH)
Katharine Nicholson MD
Collaborators involved: Massachusetts General Hospital, Harvard School of Public Health, The Broad Institute
There is growing interest in how the interplay between the intestinal microbiota (i.e., bacteria in the gut) and its host influence the onset and course of neurodegenerative diseases, potentially mediated by immune mechanisms that modulate the microglial environment. No studies have previously examined whether the overall composition of the intestinal microbiota, or specific bacterial species, are associated with ALS. In this pilot study, the intestinal microbiota of 100 people with ALS and 100 healthy controls was compared. The study used novel technology and was a collaboration project among the Harvard School of Public Health, Broad Institute, and the Neurological Clinical Research Institute at Massachusetts General Hospital, involving leading epidemiologists, microbiome analysts, and ALS clinical researchers.
NEALS Biorepository (Co-Funded by ALSFAC and the ALS Association)
Nazem Atassi, Ph.D., University of Massachusetts in Worcester, Mass
James Berry MD, Massachusetts General Hospital
James Berry, MD, Massachusetts General Hospital
The NEALS Biorepository project encompassed three sub-projects: 1) NEALS Biorepository Infrastructure Improvements, 2) Cross-Sectional ALS Biofluid Biomarker (CABB) Study, and 3) Longitudinal ALS Biofluid Biomarker (LABB) Study.
The Biorepository Infrastructure Improvements included procedural, physical, and information technology improvements to the NEALS Biorepository to improve sample security, encourage sharing, and reduce turnaround time. The infrastructure improvements enabled the distribution of over 4300 vials of biofluids over the course of the project.
The CABB Study was a new study conducted at multiple NEALS clinical sites to collect blood, DNA, and clinical information from a large group of people with ALS to expand the biorepository.
The LABB Study was a study aimed at collecting blood, DNA, RNA, spinal fluid, and clinical information from patients every four months over the course of their disease, as this type of longitudinal sample collection plus clinical data is enormously helpful for biomarker and diagnostic identification.
Funding: ALSFAC and the ALS Association
Web site: Northeast Amyotrophic Lateral Sclerosis Consortium (NEALS)
NeuroBANK as an Accelerated Clinical Research Environment
Meric Cudkowicz MD, Massachusetts General Hospital
Alex Sherman, Massachusetts General Hospital
NeuroBANK™ is a patient-centric clinical research platform that allows for the capture and aggregation of clinical and clinical research data from simultaneously-running research projects and the linking of these data with biospecimen repositories, image banks and genetic information. Embedded Global Unique patient Identifier (GUID) technology allows for the generation of patient-specific ID's that uniquely and securely identify a patient without a risk of exposure of that patient's true identity. Unlike any other existing platform for ALS clinical research, NeuroBANK™ makes it possible for the information captured from a patient participating in multiple clinical studies to be captured and linked within in a single system, thus enabling a deeper assessment of patient data.
The development of NeuroBANK™ allows for a standardized patient-centric approach to clinical research in ALS with information linked across studies, locations and modalities. Standard Common Data Elements, standard operating procedures and GUID technology enables accelerated study review, approval, deployment, and patient enrollment, as well as improving the ALS clinical research community's ability to leverage precious clinical data.
Papers summarizing results and findings:
Web site: neurobank.org
Nonclinical Safety Evaluation of AMX0035 to Support Translation to Clinical Trials
Joshua Cohen, Amylyx Pharmaceuticals
Justin Klee, Amylyx Pharmaceuticals
Shayne Gad PhD, Gad Consulting Services
Dexter Sullivan MS, Gad Consulting Services
Neurodegeneration and neurotoxic inflammation are hallmarks of ALS and together form a vicious cycle that is one of the key drivers of functional decline in patients. Our lead candidate, AMX0035, is a proprietary combination of two compounds that is designed to break this cycle, thereby halting clinical progression. Based on strong in-vitro and in-vivo results, we now seek to evaluate our promising therapeutic in patients with ALS.
Nonclinical safety studies, also called toxicology studies, are the essential FDA-required battery of tests needed to translate a therapy from the lab to the clinic. We met with the FDA in a pre-IND meeting and received consent that our safety program would be sufficient to support our first clinical trial. As of September 16, 2015, we are approximately halfway through these safety studies, and have completed:
1) The Ames Test
2) Evaluation of Maximum Tolerated Dose in Rat and Mini-pig
3) Dose Range Finding in Rat (mini-pig is currently underway)
4) Development of Bioanalytical Methods
Following completion of our nonclinical safety program in early 2016, we will file an IND with the FDA to run a first-in-human clinical trial. We are very grateful to ALS Finding a Cure for their support for these pivotal studies that will bring AMX0035 to patients in need.
The FDA Advisory Committee recently voted 7-2 supporting approval for for Amylyx. The following link has details: https://www.the-scientist.com/news-opinion/independent-fda-advisory-panel-recommends-approving-als-drug-70466
ALS Finding a Cure Providing the Initial Funding for Amylyx
Web site: http://www.fiercebiotech.com/biotech/als-upstart-amylyx-gains-3m-grant-to-start-combo-trial
http://www.prnewswire.com/news-releases/the-als-association-and-als-finding-a-cure-announce-joint-funding-support-for-amylyx-clinical-trial-of-amx0035-for-the-treatment-of-als-300300955.html
http://www.businesswire.com/news/home/20160822005017/en/Amylyx-Announces-5-Million-Series-Financing-Support
Nuclear Pore
Jeff Rothstein (JHU)
Clotilde Lagier-Tourenne (MGH)
To investigate the biology of nuclear pore dysfunction in autopsied brain tissue from ALS patients, stem cells derived from ALS patients, and within new rodent models, and ultimately to use these tools to probe new candidate therapies targeting nucleocytoplasmic transport.
SPINE ALS
Nazem Atassi MD, Massachusetts General Hospital
The goal of this project is to measure spinal cord inflammation using [11C]PBR28-PET in 10 people with ALS compared to 5 healthy volunteers. Positron emission tomography (PET) is a technology that allows accurate measurement of certain proteins or metabolites in living people. We are using a PET tracer (contrast) called PBR28 that binds to active inflammatory cells and allows us to measure and localize brain inflammation. We were able to demonstrate increased inflammation in the areas that control voluntary muscle movements (e.g., motor cortex) in people with ALS. Zucher N, Lawson R, Loggia M, Chonde DB, Izquierdo D, Akeju O, Catana C, Rosen B, Cudkowicz ME, Hooker J, Atassi N. Microglial Activation in Individuals with Amyotrophic Lateral Sclerosis. Neuroimage Clin 2015 (PMC 25685708)
The SPINE ALS project will build on our previous findings in the brain and demonstrate feasibility and relevance of imaging spinal cord inflammation as a molecular biomarker of lower motor neuron degeneration in people with ALS. A positive signal in this pilot study will provide the needed data to scale up and conduct a larger multi-center study in collaboration with General Electric (GE) using GE-180. This would nicely dovetail the ongoing TRACK ALS project and leverage the exciting collaboration between these sites and GE.
Target ALS collaboration
A collaborative project with Target ALS, launched in 2016-7 to co-fund 5 academic-industry consortia on the following topics
Project to optimize drug-like properties of a drug company's proprietary compounds that rescue TDP43, FUS, and C9orf72-derived di-peptide repeat toxicity in yeast, neurons, C. Elegans, and human iPSCs
Project to identify small molecules that inhibit the formation or accelerate the resolution of stress granules using patient derived iPSCs and determine their effects on neuronal viability and then use these to identify potential lead compounds with drug-like properties
To develop robust preclinical data supporting an inhibitor of nucleocytoplasmic transport in order to advance to Phase I/II clinical trial
To develop a gene therapy approach targeting non-sense mediated decay as a therapy against TDP43 and FUS-mediated toxicity
Developing human antibodies against di-peptide repeats as a therapeutic approach to C9 ALS
Web site: https://www.targetals.org/research/funded-consortia
TRACK-ALS: Imaging and Biofluid Biomarkers in Amyotrophic Lateral Sclerosis (MGH, GE, Methodist, Cedars)
Nazem Atassi MD,
Joseph Masdeu, MD, PHD
A. Nadeem Ishaque PhD
Suma Babu, MGH
Investigator(s):
A. Nadeem Ishaque PhD, Vladimir Reiser PhD, Luca Marinelli PhD, Merit Cudkowicz MD, Nazem Atassi MD, Stanley Appel MD, Joseph Masdeu MD, PHD, Clive Svendsen PhD
Collaborators involved: The Methodist Hospital Research Institute, Massachusetts General Hospital, GE, and Cedars-Sinai Medical Center, ALS Association
The overall goal of this project is to identify new imaging markers of ALS that can be used to accelerate ALS diagnostic timelines and the pace of ALS drug development.
The study is focused on comparing MRI signals between 50 people with ALS and 50 healthy volunteers, and to study these MRI signals over time in relationship with ALS clinical presentation, disease progression, and comprehensive biomarkers profiling including DNA, IPSC lines and inflammatory blood-based markers. A subset of these patients are also undergoing positron emission tomography (PET) to show the location and degree of brain inflammation in people with ALS. Lastly, a related study (SPINE ALS) uses MRI and PET technology to explore the ability to detect signals in the spinal cord of ALS patients. These studies leverage GE Healthcare's work in TBI and bring GE's imaging expertise to a study in ALS.
Web site: ClinicalTrials.gov
Traumatic Brain Injury (TBI) in ALS
Gretchen Thomsen, PhD, Cedars-Sinai Medical Center
Eric Ley, MD, Cedars-Sinai Medical Center
Collaborators involved: Robert Baloh, MD/PhD, Cedars-Sinai Medical Center
The hypothesis behind this study was that the brain plays a critical role in ALS disease onset and therefore if one could prevent brain cell death this could delay disease onset and enhance survival of spinal motor neurons. This hypothesis was tested through a series of experiments in both SOD1G93A rat and C9orf72 mouse models. The study found that administering a controlled chronic traumatic brain injury did exacerbate disease progression and decrease time to disease onset in the rat SOD1 ALS model, however an acute TBI did not exacerbate death. The C9orf72 studies are ongoing under a no-cost extension.
Understanding SOD1 Kinetics in ALS
Tim Miller (WashU)
NIH also co-funded this study
Novel therapies are being developed for Amyotrophic Lateral Sclerosis (ALS) caused by changes in the gene superoxide dismutase 1 (SOD1). This study assessed how quickly SOD1 protein was normally cleared from the cerebrospinal fluid (CSF) that bathes the brain and spinal cord in humans. These data helped determine the optimal time to administer drugs targeting SOD1, including the ALSFAC-funded study of AAV10 SOD1 silencing, and also Biogen's Tofersen study.
Web site: https://clinicaltrials.gov/ct2/show/NCT03449212?term=SOD1+Kinetics&draw=2&rank=1
Validating/Identifying Biomarkers (Co-Funded by the ALS Association and ALS Finding A Cure)
Tim Miller, Washington University
Noah Zaitlen, UCSF
Shan Sockanathan, Johns Hopkins
The exact cause of amyotrophic lateral sclerosis remains unknown, and there are no tests to diagnose the disease or follow its progression. Such tests, known as biomarkers, would be invaluable to speed the development of novel therapies for ALS. In recent years, ALS scientists have begun to identify promising potential biomarkers in the blood and spinal fluid of people with the disease. The next step to build on these discoveries, in many cases, is to test larger numbers of biofluid samples to confirm the findings. Therefore, a multi-foundation collaboration spearheaded by the ALS Association issued a global call for letters of intent from academia and pharma for ideas of ways to identify and/or validate ALS biomarkers, building on our investment in developing a large repository of well annotated, quality controlled cross-sectional and longitudinally collected biosamples. ALS Finding a Cure funded 3 biomarker projects at UCSF, Johns Hopkins, and Washington University through this collaborative mechanism.
Funding: The ALS Association and ALSFAC
Web site: Biomarkers | The ALS Association, ALS Accelerated Therapeutics (ALS ACT) | The ALS Association


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The Board of Directors of Jacobs has declared a quarterly cash dividend payable to shareholders in the amount of $0.19 per share of Jacobs common stock.
KPMG's Manny Fernandez Named to Jacobs Board of Directors
After more than 36 years advising both public and private companies, Fernandez is retiring from KPMG LLP on September 30, 2020 and joining the Jacobs board effective Oct. 5, 2020.
Jacobs Completes Successful Test Campaign of KeyRadar in AgilePod
The radar system combines multiple bands with sophisticated processing and detection/recognition software to find concealed targets in the most challenging operational environments.
UK Water Net Zero Carbon: Quantifying the Benefits of Biosolids to Land
By quantifying the carbon benefits of biosolids to land, the U.K. water industry has a key opportunity to support a fair and balanced narrative around biosolids, to better recognise benefits and to develop a future looking framework for sustainable, circular resource use.
A High-Flying New Addition to One of Ohio's Busiest Freeways
Much like playing Tetris, find the answer to how Jacobs designed a bridge more than 200-feet-tall and 4,150-feet-long built in the 90-foot space between two existing bridges.
Dr. John W. Mogge Jr. Honored with Environmental Lifetime Achievement Award
John began his 45-year environmental career as an instructor on active duty to the U.S. Air Force Institute of Technology (AFIT) in Dayton, Ohio. He currently serves as the Solutions and Technology Director for Jacobs' Federal Buildings & Infrastructure business. Read more about his incredible journey.
Jacobs Plays Key Role in First Multi-state Truck Pilot Exploring Mileage-based User Fees in US
Looking to impress your circle at the next virtual trivia night? Try this fact: did you know Jacobs served as prime consultant for the premier multi-state truck pilot exploring innovative mileage-based user fees in the U.S.? Score some bonus points with the full details in this article.
Jacobs and WIFIA: Reinventing Water Infrastructure Financing
Jacobs Strategic Consulting Business & Finance Leader Dennis Jackson discusses the ins-and-outs of the Water Infrastructure and Finance Innovation Act, and how Jacobs can help secure funding to bring critical projects to fruition in this piece.
Jacobs Secures Place on Highways England's Technical Advisor Framework
With investments totaling more than $1.27 billion (£1 billion) over the six-year framework, it is hoped that the road schemes in the framework will boost the economy and make the network safer and more reliable.
Jacobs Transit Leader Recognized with American Public Transportation Association (APTA) Outstanding Public Transportation Business Member of the Year Award
What if we showed you how APTA's Outstanding Public Transportation Business Member of the Year Award-winner, Freddie Fuller, blends leadership and diversity to make the transit industry better? Read about Freddie's latest recognition and how he makes the transit industry better role by role.
Ever Wonder What an Internship During a Pandemic Looks Like?
Thanks to our intern class of 2020 for their flexibility, positivity and contributions to our first-ever virtual #internship program. Hear about their experience at Jacobs in this article.
Innovation as a Service Tool Scores Impact Award Nod for Best New Initiative
Jacobs has been chosen as a finalist for Innovation Leader's 2020 Best New Initiative Awards. Explore more about our finalist and tool for organizational innovation, Innovation as a Service.
Jacobs Helps NASA Streamline NEPA Compliance for Nuclear-enabled Space Missions
Missions into deep space and extended missions to distant planetary surfaces use radioisotope heater units (RHUs) for heat, due to the functional limitations of solar heat and the limited life capabilities of electrical heat from batteries. The Jacobs team, working in partnership with NASA, the U.S. Department of Energy, U.S. Air Force and the Federal Aviation Administration, developed a first-of-its-kind Programmatic Environmental Assessment for the use of RHUs in spacecraft launched from Kennedy Space Center and Cape Canaveral Air Force Station in Florida.
Jacobs Helps Devise Semi-Autonomous Scouting System for British Army to 'Map the Gap'
Jacobs is part of the team selected by the U.K.'s Ministry of Defence to devise a new system to help the British Army cross water more safely. Discover how our 6th Sense data analytics system is a key part of the solution in helping units to carry out vital reconnaissance tasks without putting personnel at risk:
Wheels Up (Soon) for National Aviation Day 2020
Celebrated in the U.S. on Orville Wright's – one of aviation's pioneers – birthday, National Aviation Day is the oldest aviation-themed holiday. What President Franklin D. Roosevelt began in 1939, is recognized today in airports and museums across the country to celebrate the advancements in the industry and look to the future skies. Jacobs' Vice President of Aviation for the Americas Steve Pelham reflects on why he's drawn to the aviation industry and how Jacobs is playing a role in helping the industry pivot toward tomorrow.
Retired Four-Star General Vincent K. Brooks Named to Jacobs Board of Directors
Widely respected as a speaker and leader of innovative organizations within and beyond the military, his areas of expertise include leadership in complex organizations, inclusion and diversity, national security, international relations, military operations, combating terrorism and countering the proliferation of weapons of mass destruction.
Jacobs Releases Blueprint for Creating Social Value Through Infrastructure Investments
What if infrastructure could be planned, delivered, built and operated to generate enduring social value at scale to help overcome some of the most entrenched social issues in our communities?
Jacobs Appointed to Transport for London's Professional Services Framework
The contract enables the whole of the TfL organization, the Greater London Authority and London's Borough Authorities to access contemporary consultancy support to enable greater efficiency and effectiveness in project and program delivery.


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Closing the gap between rhetoric and reality on race
By MetaNews June 8, 2020 335
The death of George Floyd has prompted soul-searching across the US, not least in boardrooms. Big companies have rushed out messages saying that they, too, believe black lives matter. Those messages have been met with an understandably cynical response, with critics pointing to the near-complete absence of black people at the top of large corporates and the longstanding relative underrepresentation of the African-American population. The contrast between public professions of support and the reality of US business life has reignited the debate about the dearth of ethnic minorities in boardrooms.
Just four Fortune 500 companies are run by black chief executives. In the UK, the picture is similarly bleak; the Parker review, set up to improve ethnic diversity on the boards of UK-listed businesses, in February revealed that 37 per cent of companies in the FTSE 100 had no non-white board members. Sharon White, chairman of department store chain John Lewis, is an oft-cited example of a rare black woman at the top of a large British company.
Today's outcry is far from the first time that the US has had to confront its poor record on black economic empowerment. After the Civil Rights Act of 1964, which made racial and religious discrimination illegal, many companies set up diversity programmes. They have waxed and waned, but the numbers do not lie — only 17 black people have led Fortune 500 companies since the turn of the century, a pitiful return given that blacks make up nearly 14 per cent of the population.
If more companies are alert to the issue and executives are committed to advancing diversity, why the reality gap? Studies show that despite good intentions of employers they often fall short of creating equitable workplaces for black employees; a recent study by the Center for Talent Innovation found nearly one in five black professionals felt someone of their ethnicity would never achieve a top position in their company. The same report identified a brain drain of black executives opting to start their own businesses.
One of the challenges has been that in many cases companies' diversity initiatives have focused simply on getting numbers through the door. A greater emphasis on gender diversity has meant that progress on other forms — such as racial or nationality — has suffered. Critics have also voiced concerns that companies have tended to focus on "tokenism" for the sake of diversity, believing that by simply appointing a black person to the board the issue has been addressed. True diversity will only come if change happens lower down.
There are reasons to be hopeful. More organisations are promising to hire a greater number of people of colour. A millennial workforce has shown it looks beyond mere financial rewards to other issues such as the treatment of minorities. Investors, too, must play their part; multiple studies show that racial equality, like gender equality, is not just a moral issue but makes business sense. Research has shown that diverse and inclusive teams outperform their peers. Reporting also matters; investors should push for greater disclosure of racial and ethnic diversity.
Company executives should acknowledge the influence they can wield to drive meaningful policy change. Many have found their voices in recent days to comment on what are deep-rooted social issues. They should use their lobbying power to support policies and politicians that advance diversity — and campaign against those that do not.
French Shares Up By Close, CAC 40 Rose .34%
By Billy Houghton December 5, 2020
CAC 40 Index Up .23% As Part of An Upward Trend
Three "Penny Shares" To Buy Today
Peloton Shares Hit Huge Surge At Close of Trade
USD Stops Fall After Feds Halt Emergency Talks
DOW Jones Industrial Climbs To New Highs Today