On January 30, 2012, Stem Cells Inc. announced the publication of preclinical data demonstrating that its proprietary HuCNS-SCr cells (purified human neural stem cells) protect host photoreceptors and preserve vision in an animal model of retinal disease. The preclinical results are highly relevant to human disorders of vision loss, the most notable of which is dry age-related macular degeneration (AMD). The study is available online at and will be featured as the cover article in the February issue of the international peer-reviewed European Journal of Neuroscience.
This research was conducted in collaboration with a team of researchers led by Raymond Lund, Ph.D., Professor Emeritus of Ophthalmology, and Trevor McGill, Ph.D., Research Assistant Professor at the Casey Eye Institute, Oregon Health and Science University.
The results of the study show that photoreceptors, the key cells of the eye involved in vision, were protected from degeneration following transplantation of HuCNS-SC cells into the Royal College of Surgeons (RCS) rat. The RCS rat is a well-established model of retinal disease which has been used extensively to evaluate potential cell therapies. Moreover, the number of cone photoreceptors, which are responsible for central vision, remained constant over an extended period, consistent with the sustained visual acuity and light sensitivity observed in the study. In humans, degeneration of the cone photoreceptors account for the unique pattern of visual loss in dry AMD.
"These results are the most robust shown to date in this animal model," said Dr. Lund, one of the study's lead investigators. "One of the more striking findings is that the effect on vision was long-lasting and correlated with the survival of HuCNS-SC cells more than seven months after transplantation, which is substantially longer than other cell types transplanted into this same model. Also important, particularly for potential clinical application, was that the cells spread from the site of initial application to cover more of the retina over time. These data suggest that HuCNS-SC cells appear to be a well-suited candidate for cell therapy in retinal degenerative conditions."
Alexandra Capela, Ph.D., another of the study's investigators and a senior scientist at StemCells, commented, "This study showed that the HuCNS-SC cells persisted and migrated throughout the retina, with no evidence of abnormal cell formation, which supports our hypothesis of a single transplant therapeutic. With this research, then, we have shown that vision can be positively impacted with a simple approach that does not require replacing photoreceptors or the RPE cells. We look forward to investigating this promising approach in the clinic later this year."
Following the above announcement, the company, on February 2nd, announced that it received authorization from the U.S. Food and Drug Administration (FDA) for a Phase I/II clinical trial of the company's proprietary HuCNS-SCr product candidate (purified human neural stem cells) in dry age-related macular degeneration (AMD), the most common form of AMD.
AMD is the leading cause of vision loss and blindness in people over 55 years of age, and approximately 30 million people worldwide are afflicted with the disease. There are no approved treatments for dry AMD.
"With the approval of this trial, we have accomplished something truly unique in the stem cell field, which is the extension of clinical testing of our proprietary human neural stem cell platform to all three elements of the central nervous system: the brain, spinal cord and eye," said Martin McGlynn, President and CEO of StemCells, Inc. "The preclinical data supporting our IND is particularly compelling and we look forward to getting this trial underway."
The Phase I/II trial will evaluate the safety and preliminary efficacy of HuCNS-SC cells as a treatment for dry AMD. The trial will be an open-label, dose-escalation study, and is expected to enroll a total of 16 patients. The HuCNS-SC cells will be administered by a single injection into the space beneath the retina. Patients' vision will be evaluated using conventional methods of ophthalmological assessment at predetermined intervals over a one-year period. Patients will then be followed for an additional four years in a separate observational study.
Editor's Notes: The company has not as yet disclosed where the clinical trial will be held. But, since the pre-clinical work was done at Casey Eye (OHSU), my guess is that that's where the clinical trial will be carried out. When the company does announce this information, I will pass it along to you.
When Stem Cells Inc. does begin its clinical trial, it will be joining two other companies that have approved clinical trials using stem cells underway to treat dry AMD: Advanced Cell Technology and Centecor/J&J. ACT has Phase I/II trials underway at two U.S. sites, while awaiting approval for a site in London, while Centecor also has a Phase I/II trial underway at two U.S. sites.
For more information on these and other stem cell clinical trials, request my table, Stem Cell Therapy in Ophthalmology by Application.
Researchers at several universities and laboratories collaborated to treat dogs afflicted with the x-linked form of retinitis pigmentosa, to deliver the therapeutic RPGR gene specifically to the diseased rods and cones, which led to functional and structural recovery. This is the first proof that this condition is treatable in an animal model and the researchers feel the results are promising and relevant for translation to humans afflicted with this disease.
The results have been published in the journal, Proceedings of the National Academy of Sciences.
Members of a University of Pennsylvania research team have shown that they can prevent, or even reverse, a blinding retinal disease, X-linked Retinitis Pigmentosa, or XLRP, in dogs.
The disease in humans and dogs is caused by defects in the RPGR gene and results in early, severe and progressive vision loss. It is one of the most common inherited forms of retinal degeneration in man.
"Every single abnormal feature that defines the disease in the dogs was corrected following treatment," said lead author William Beltran, assistant professor of ophthalmology at Penn's School of Veterinary Medicine.
"We were thrilled," said senior author Gustavo Aguirre, professor of medical genetics and ophthalmology at Penn Vet. "The treated cells were completely normal, and this effect resulted from introducing the normal version of the human gene into the diseased photoreceptor cells."
The similarities between humans and dogs, in terms of both eye anatomy, physiology, disease characteristics and positive response to this gene therapy, raise hope for a clear path to human therapies.
Beltran and Aguirre collaborated with Artur Cideciyan and Samuel Jacobson at the Scheie Eye Institute, part of the University of Pennsylvania's Perelman School of Medicine. This achievement results from more than 10 years of close collaboration between the scientists at Penn's Veterinary and Medical Schools and the University of Florida.
In addition to others at Penn Vet, Scheie, and Florida, researchers at the Universities of Michigan and Massachusetts and the National Eye Institute at the National Institutes of Health contributed to the research.
The gene therapy approach used takes advantage of a viral vector - a genetically modified virus that doesn't cause disease and is unable to divide -- to deliver the therapeutic RPGR gene specifically to diseased rods and cones. In the absence of treatment, these cells malfunction and progressively die.
The research team has previously successfully applied a similar approach to two other heritable vision disorders that occur in both humans and dogs: Leber congenital amaurosis (LCA) and achromatopsia. The present study was more challenging, as it was necessary to target both main classes of photoreceptor cells.
While the exact disease mechanism of the RPGR form of XLRP is still unknown, the researchers were able to successfully treat dogs with two different RPGR mutations. The mutations disrupt photoreceptors in different ways, but both ultimately cause them to become useless for vision. While this form of blindness is rare in dogs, it is common in humans. Patients with XLRP usually begin to lose night vision as children and become almost totally blind by middle age.
This is the first proof that this condition is treatable in an animal model; a single subretinal injection administered to the diseased dogs led to functional and structural recovery. The dogs' recovery was assessed using a variety of methods that are used clinically in patients, such as electroretinography and optical coherence tomography.
The researchers feel the results are promising and relevant for translation to the clinic.
"We are intervening to treat both classes of photoreceptor cells, rods and cones, and that has never been done before in a large animal model," Beltran said. "And not only can we prevent the disease onset but also restore the remaining photoreceptors cells to normal once the disease is ongoing."
While the ability to repair both rods and cones was itself a first, the research team went further, showing that its treatment also repaired the photoreceptor connections to other retinal neurons that eventually send visual signals to the brain, another first.
"This not only provides hope for reversing XLRP but potentially for any form of photoreceptor degeneration," Aguirre said. "Altered inner retinal wiring is a common feature for these diseases that has been considered irreversible.
"The study required a combination of genetic tools and surgical technique to make sure the therapy targeted only the diseased cells. The viral vector had to be injected in the sub-retinal space so as to be in close proximity to the photoreceptors. Likewise, you need to ultimately deliver the therapy to the right location of the retina," Aguirre said.
"In the human disease, careful characterization of the areas of the retina that need to be treated is going to be critical for therapy to succeed in the clinic," Cideciyan said.
The genetic aspect of the viral vector used in this study involved a double safeguard. The first safety feature was to use a viral vector that is known to predominantly target both rods and cones but not other cells. The second safeguard involved attaching the healthy RPGR gene to a "promoter," a piece of genetic code that would "switch on" the gene only if the virus penetrated the correct cell.
Selecting the right promoter was critical; the lead researchers at the University of Florida, William W. Hauswirth and Alfred S. Lewin, had to find one that that would be turned on exclusively in rods and cones. This way, even if the virus made its way to a non-photoreceptor cell, that cell would not start activating the RPGR gene.
That both the promoter and the RPGR gene it activates are taken from humans is a strong sign that the treatment may be translatable to patients.
"While there is still much work to do to assess long-term efficiency and safety with this approach, there is hope that this vector and knowledge could be used in a few years to treat the many patients losing vision from XLRP," Jacobson said.
A new gene therapy method developed by University of Florida researchers has the potential to treat a common form of blindness that strikes both youngsters and adults. The technique works by replacing a malfunctioning gene in the eye with a normal working copy that supplies a protein necessary for light-sensitive cells in the eye to function. The findings are published today (Monday, Jan. 23) in the Proceedings of the National Academy of Sciences online.
Several complex and costly steps remain before the gene therapy technique can be used in humans, but once at that stage, it has great potential to change lives.
"Imagine that you can't see or can just barely see, and that could be changed to function at some levels so that you could read, navigate, maybe even drive - it would change your life considerably," said study co-author William W. Hauswirth, Ph.D., the Rybaczki-Bullard professor of ophthalmology in the UF College of Medicine and a professor and eminent scholar in department of molecular genetics and microbiology and the UF Genetics Institute. "Providing the gene that's missing is one of the ultimate ways of treating disease and restoring significant visual function."
The researchers tackled a condition called X-linked retinitis pigmentosa, a genetic defect that is passed from mothers to sons. Girls carry the trait, but do not have the kind of vision loss seen among boys. About 100,000 people in the U.S. have a form of retinitis pigmentosa, which is characterized by initial loss of peripheral vision and night vision, which eventually progresses to tunnel vision, then blindness. In some cases, loss of sight coincides with the appearance of dark-colored areas on the usually orange-colored retina.
The UF researchers previously had success pioneering the use of gene therapy in clinical trials to reverse a form of blindness known as Leber's congenital amaurosis. About 5 percent of people who have retinitis pigmentosa have this form, which affects the eye's inner lining.
"That was a great advance, which showed that gene therapy is safe and lasts for years in humans, but this new study has the potential for a bigger impact, because it is treating a form of the disease that affects many more people," said John G. Flannery, Ph.D., a professor of neurobiology at the University of California, Berkeley who is an expert in the design of viruses for delivering replacement genes. Flannery was not involved in the current study.
The X-linked form of retinitis pigmentosa addressed in the new study is the most common, and is caused by degeneration of light-sensitive cells in the eyes known as photoreceptor cells. It starts early in life, so though affected children are often born seeing, they gradually lose their vision.
"These children often go blind in the second decade of life, which is a very crucial period," said co-author Alfred S. Lewin, Ph.D., a professor in the UF College of Medicine department of molecular genetics and microbiology and a member of the UF Genetics Institute. "This is a compelling reason to try to develop a therapy, because this disease hinders people's ability to fully experience their world."
Both Lewin and Hauswirth are members of UF's Powell Gene Therapy Center.
The UF researchers and colleagues at the University of Pennsylvania performed the technically challenging task of cloning a working copy of the affected gene into a virus that served as a delivery vehicle to transport it to the appropriate part of the eye. They also cloned a genetic "switch" that would turn on the gene once it was in place, so it could start producing a protein needed for the damaged eye cells to function.
After laboratory tests proved successful, the researchers expanded their NIH-funded studies and were able to cure animals in which X-linked retinitis pigmentosa occurs naturally. The injected genes made their way only to the spot where they were needed, and not to any other places in the body. The study gave a good approximation of how the gene therapy might work in humans.
"The results are encouraging and the rescue of the damaged photoreceptor cells is quite convincing," said Flannery, who is on the scientific advisory board of the Foundation Fighting Blindness, which provided some funding for the study. "Since this type of study is often the step before applying a treatment to human patients, showing that it works is critical."
The researchers plan to repeat their studies on a larger scale over a longer term, and make a version of the virus that proves to be safe in humans. Once that is achieved, a pharmaceutical grade of the virus would have to be produced and tested before moving into clinical trials in humans. The researchers will be able to use much of the technology they have already developed and used successfully to restore vision.
Editor's Note: The lead author of the article about the study, Dr. William Beltran, said privately that much more pre-clinical work needs to be done before entertaining thoughts on beginning human clinical trials.
In an unexpected outcome, Dr. Pravin Dugel presented the 2-year results of the CABERNET study, evaluating the use of NeoVista's VIDION ANV epimacular brachytherapy device at the Bascom Palmer Eye Institute's (BPEI) Angiogenesis, Exudation, and Degeneration 2012 Meeting in Miami on Februay 4th.
As described in the following extensive writeup from Retina Today, the Phase 3, multicenter, prospective, randomized study did not achieve its primary endpoint after two years.
As I have previously written (see Update 4), the device has been commercialized extensively in Europe and the company was hoping that promising results in the CABERNET study would lead to FDA approval for marketing in the U.S. Those plans may now be on hold until subset analysis is completed and/if a subset of patients can be identified that would benefit from use of the device.
I asked NeoVista if they wished to comment about this development, and the company said that they would have no comment at this time.
Based on visual acuity outcomes, the CABERNET study evaluating epimacular brachytherapy for the treatment of wet age-related macular degeneration (AMD) did not achieve its primary endpoint at 2 years, according to Pravin U. Dugel, MD. Dr. Dugel presented the 2-year results of the CABERNET study at the Bascom Palmer Eye Institute's (BPEI) Angiogenesis, Exudation, and Degeneration 2012 meeting in Miami.
The phase 3, multicenter, prospective, randomized CABERNET study included 457 treatment-naïve patients who were divided into 2 arms. Patients in the treatment arm (n=302) underwent strontium-90 beta radiation with epimacular brachytherapy (NeoVista) and 2 mandatory ranibizumab (Lucentis, Genentech) injections. Patients in the control arm (n=155) received ranibizumab injections following a modified PIER protocol, which included 3 initial monthly injections followed by injections once every 3 months. In the CABERNET study, patients were seen on a monthly basis, and rescue therapy was permitted, as per the investigators' discretion.
The primary endpoint of CABERNET was visual acuity, specifically, the percentage of patients losing fewer than 15 letters of vision. In patients treated with epimacular brachytherapy, 6 injections were required at the 2-year mark for a mean 2.5 letter loss. Patients treated with ranibizumab required 11 injections and achieved a mean 4.4 letter gain.
In a post-study, unplanned subgroup analysis, the investigators identified 44% of patients in the epimacular brachytherapy group who required no rescue injections through the first 12 months and 1 rescue injection through the second 12 months, with a mean 3.3 letter gain, Dr. Dugel said.
In a similar analysis, the investigators identified 25% of patients in the epimacular brachytherapy arm who required no rescue injections throughout the 2-year course of the study, with a mean gain of 5.7 letters.
Cataract formation occurred in 48% of patients in the epimacular brachytherapy arm, which was suspected to be due to vitrectomy procedures, according to Dr. Dugel. The difference in the APTC events between the 2 study groups was not clinically significant.
At the 2-year mark, there were 10 patients with suspected radiation-based retinopathy. "There are 2 important things about these patients," Dr. Dugel said. "The first being that these 10 patients had changes that were nonproliferative and nonprogressive throughout the 2-year course of the study; the second, as a group, these patients tended to do fairly well. The mean change in visual acuity was +4.4 letters of vision. None of these patients lost significant vision, and the mean number of injections was 4."
The CABERNET demonstrated an acceptable safety profile for epimacular brachytherapy at the 2-year mark and identified a subgroup of patients that tended to respond well to the treatment. However, the CABERNET study did not achieve its primary endpoint, and it is not yet known whether the subgroup of patients who benefitted from the device can be reliably and consistently identified in clinics, Dr. Dugel concluded.
"At the end of the day, I think it is important to keep this study in proper perspective," Dr. Dugel said. "It was started in 2006 when there were few treatment alternatives. In retrospect, the CABERNET study should not have included treatment-naïve patients, but rather, should have treated previously ranibizumab-treated patients only. The CABERNET study should have [also] placed a lot more importance on probe placement."
Editor's Note: It should be noted that Dr. Dugel is a consultant to and minority shareholder of NeoVista.
In an announcement today from the Foundation Fighting Blindness, and confirmed by Oxford BioMedica, the Casey Eye Institute of the Oregan Health & Science University (OHSU) is preparing to treat the first Usher Syndrome patient under the clinical protocol designed by Oxford BioMedica using its UshStat gene therapy treatment.
March 6, 2012 - The first-ever gene therapy for Usher syndrome, a devastating condition that causes both blindness and deafness, has moved into a Phase I/IIa clinical trial at the Foundation-funded Casey Eye Institute, Oregon Health & Science University (OHSU). The research team, led by Dr. Richard Weleber, is preparing to treat its first patient.
Developed by Oxford BioMedica, a biopharmaceutical company in the U.K. and a Foundation partner, the UshStat treatment is designed to halt vision loss in people affected with Usher syndrome type 1B, which is caused by defects in the MY07A gene. Based on results in lab studies, researchers believe a single UshStat treatment may last several years, perhaps a lifetime.
"We are delighted to see Oxford's innovative gene therapy for Usher 1B move into human studies. It is a critical milestone in our campaign to overcome vision loss from a particularly challenging condition," says Dr. Stephen Rose, the Foundation's chief research officer. "UshStat is great news for the Usher syndrome community, because there are virtually no vision-related treatment options available for any form of the disease. While the treatment is for Usher 1B, success in the trial will open the door for using gene therapy to treat other forms of Usher syndrome."
UshStat is the third Oxford BioMedica gene therapy to move into a clinical trial. StarGen, the company's gene therapy for Stargardt disease, is in a Phase I/IIa human study at OHSU and the Centre Hospitalier Nationale d'Ophthalmologie des Quinze-Vingts in Paris. The company's RetinoStat, a gene therapy for wet age-related macular degeneration, is in a Phase I clinical study at Wilmer Eye Institute at Johns Hopkins Hospital in Baltimore, Maryland.
Oxford says that the first six patients in the RetinoStat trial and the first four in the StarGen study are doing well. No safety issues or adverse events have occurred. The company will report additional results for RetinoStat in the first half of 2012 and for StarGen in the second half of the year.
The two-year UshStat study will enroll 18 patients affected by Usher syndrome type 1B. One eye of each patient will be injected with the therapy. The trial will evaluate the treatment's safety as well as changes in retinal function of the treated eye versus the untreated eye.
To participate in the UshStat trial, patients will need to be 18 years or older and have had a genetic test confirming the diagnosis of Usher syndrome type 1B. For more information on trial participation, visit the clinical trials page of the Foundation's website, which requires registration.
The UshStat treatment is contained in a tiny drop of liquid that is injected beneath the retina and absorbed by retinal cells in a matter of hours. The treatment uses Oxford's LentiVector gene delivery technology, a re-engineered virus, to enable healthy copies of the MYO7A gene to penetrate the cells. A key benefit of the LentiVector technology is its ability to deliver large genes, like MYO7A, which other viral systems are not able to deliver.
Usher syndrome is the leading cause of combined deafness and blindness in the world. It affects approximately 45,000 people in the United States. There are three primary types of Usher syndrome, designated by numerals, and 12 subtypes, designated by letters.
"We are excited about the potential for our powerful gene therapy technology to save and restore vision, and we are grateful to the Foundation Fighting Blindness for playing a critical role in moving it out of the lab and into clinical trials. It has been an outstanding partnership," says Stuart Naylor, Ph.D., chief scientific officer, Oxford BioMedica.
In addition, Oxford BioMedica provided some updated information about its other ophthalmic gene therapy programs, as part of the release of its end of year report.
Six patients have been treated with RetinoStat in the on-going US Phase I study in neovascular "wet" age-related macular degeneration (AMD). Three patients received the first dose level, three received the second dose level and the third patient cohort (dose level 3) is underway. The open label, dose escalation Phase I study will enroll 18 patients with "wet" AMD at the Wilmer Eye Institute at Johns Hopkins, Baltimore (USA). Led by Professor Peter Campochiaro, the study will evaluate three dose levels and assess safety and aspects of ocular physiology. Oxford BioMedica is on track to announce first results in H1 2012.
There are currently no approved treatments for Stargardt disease and Usher syndrome type 1B and other potential strategies do not target the root cause of the disease. As such, StarGen and UshStat have received both European and US Orphan Drug Designation which brings development, regulatory and commercial benefits.
In June 2011, the first patient in the StarGen Phase I/IIa study in Stargardt disease was treated in the US.
In July 2011, the French regulatory agency (AFSSAPS) approved the opening of a second clinical site in France. In the US, the study is led by Professor David Wilson at the Oregon Health & Science University, Portland, Oregon. In France, Professor Jose-Alain Sahel leads the study at the Centre Hospitalier National D'Opthalmologie des Quinze-Vingts, Paris.
Four patients have been treated to date at the first dose level and the second cohort using dose level 1 in earlier-stage patients is underway. The open label, dose escalation Phase I/IIa study will enroll up to 28 patients and will evaluate three dose levels for safety, tolerability and aspects of biological activity. First results are expected in H2 2012.
In February 2012, the UshStat Phase I/IIa study in Usher syndrome type 1B commenced in the US at the Oregon Health & Science University's Casey Eye Institute. Led by Professor Richard Weleber as Principal Investigator, the open label, dose escalation Phase I/IIa study will enrol up to 18 patients and will evaluate three dose levels for safety, tolerability and aspects of biological activity. Initial results are expected in H2 2012.
In October 2011, Oxford BioMedica entered into a research and development collaboration with Mayo Clinic, Rochester (USA) to develop a novel gene therapy for the treatment of chronic glaucoma. Under the terms of the agreement, Mayo Clinic and Oxford BioMedica will undertake pre-clinical studies to establish the feasibility of treating glaucoma using Oxford BioMedica's proprietary LentiVector gene delivery technology expressing a COX-2 gene and a PGF-2α receptor gene to reduce intraocular pressure.
Since the start of the collaboration, the teams have successfully initiated the first pre-clinical study which aims to demonstrate gene transfer using Oxford BioMedica's LentiVector platform technology to target ocular tissues following transcorneal administration. Preliminary results from this study are encouraging and indicate effective and robust gene transfer into the target ocular tissues. A second pre-clinical study is expected to begin in Q2 2012 to evaluate the lowering of intraocular pressure following administration of the collaboration's Glaucoma-GT.
I just learned this afternoon, of a start-up company, MitoChem Therapeutics, which is apparently an outgrowth of the Vision Research program at the Ophthalmology department at the Medical University of South Carolina. Two of their scientists, Drs. Rohrer and Beeson, have been looking into compounds that can provide "energy" to "reduced capacity" mitochondria in retinal cells that are possibly at the root of retinal degenerations in such diseases as retinitis pigmentosa and macular degeneration.
The Foundation Fighting Blindness is providing $2 million to the company to support their research. After screening a library of 50,000 drug compounds, they have apparently identified three compounds that appear to boost mitochondrial function, and will now attempt to identify which one will work best in people as an eye drop, and move it into a clinical trial.
March 2, 2012 - A key to survival for any organism, plant or animal, is energy. And, in humans, every cell gets its energy from a tiny, organ-like structure called a mitochondrion. It operates like a power plant, providing the energy needed to stay alive and functioning. Among their many functions, mitochondria combine sugar and oxygen, which serve as the cells' supply of fuel.
One consequence of most retinal degenerations, including retinitis pigmentosa and macular degeneration, is that mitochondria operate at reduced capacity, because of disease-related stress. Ultimately, photoreceptors, the cells in the retina that provide vision, are lost.
The Foundation Fighting Blindness is giving $2 million to MitoChem Therapeutics, a start-up company which, thanks to prior Foundation support, has identified three compounds that appear to boost mitochondrial function and, thus, show potential for slowing vision loss caused by a variety of retinal degenerations. The goal is to determine which one will work best in people and move it into a clinical trial.
Dr. Stephen Rose, chief research officer of the Foundation, says that finding treatments which benefit people with a range of conditions is an important part of the Foundation's mission. "We are always excited by cross-cutting therapies. With defects in more than 200 genes causing these retinal conditions, we are very attracted to potential treatments like MitoChem's that can help a lot of people, including those for whom we can't find the gene causing their disease."
In 2009, the founders of MitoChem - Dr. Barb Rohrer, an expert in retinal degenerations, and Dr. Craig Beeson, a medicinal chemist - screened a library of 50,000 compounds to identify those which enhanced mitochondrial function. They used a high-throughput screening technology combining robotics, data processing systems and sensitive detectors to determine, both quickly and efficiently, which compounds have vision-saving properties. Three emerged from that process and subsequently showed good results in preserving and even restoring vision in animal models of retinal degeneration.
With the goal of moving a cross-cutting treatment into a clinical trial, MitoChem will now: determine which compound is the best drug candidate; develop a drug formulation that will work as an eye drop; and conduct further toxicity and efficacy studies to ensure the drug is ready for human studies.
An important focus of the project is meeting FDA requirements to gain authorization to launch the study. "The FDA will look closely at everything from animal model study results, to manufacturing and production of the compound, to the actual design of the trial before giving MitoChem the OK to begin the study in humans," says Dr. Rose. "We will be working closely with Drs. Rohrer and Beeson to help ensure that those requirements are met. It's challenging and expensive, but it's what we have to do to get the treatment into and through the trial and out to the people who need it."
Finally, some good news for Alimera (and pSivida). A few days ago, the company announced that it had received a positive outcome to the Decentralized Procedure (DCP) for Iluvien in Europe. Iluvien is now expected to be the first sustained release pharmaceutical in the European Union for the treatment of diabetic macular edema (DME).
The regulatory process will now enter the national phase of the DCP in which the Reference Member State (RMS), the Medicines and Healthcare products Regulatory Agency of the United Kingdom (MHRA), and each Concerned Member States (CMS) grants its national license. The CMS include Austria, France, Germany, Italy, Portugal and Spain.
While it appears that this drug for DME is not going to be moving forward in the US (see Update 4: FDA Turns Down Alimera's NDA for Approval of Iluvien Again), approval for marketing in Europe appears on track. It has been estimated that the European market may be the same size as the US market.
Just for reference, Iluvien is licensed by Alimera from pSivdia.
For more on the background of this unique sustained release drug for the treatment of retinal disease, please see my original report on the product, and the four updates, listed (and linked) at the end of this writeup.
Alimera Sciences, Inc., a biopharmaceutical company that specializes in the research, development and commercialization of prescription ophthalmic pharmaceuticals, today announced the positive outcome of the Decentralized Procedure (DCP) for Iluvien in Europe. The announcement follows the issuance of the Final Assessment Report from the Reference Member State (RMS), the Medicines and Healthcare products Regulatory Agency of the United Kingdom (MHRA), and the agreement of all the Concerned Member States (CMS) that Iluvien is approvable.
The regulatory process will now enter the national phase of the DCP in which the RMS and each CMS grants its national license. The CMS include Austria, France, Germany, Italy, Portugal and Spain. Iluvien will be indicated for the treatment of vision impairment associated with chronic DME considered insufficiently responsive to available therapies.
The International Diabetes Federation estimates that, in these seven countries alone, 22.1 million people are currently living with diabetes. By comparison, the Centers for Disease Control and Prevention estimate that Americans with diabetes now number 25.8 million. Alimera estimates that within the seven CMS countries, 1.2 million people suffer from DME.
"Achieving a favorable conclusion for Iluvien in Europe is a significant milestone for Alimera and very encouraging for the many patients with this challenging chronic disease," said Dan Myers, president and chief executive officer, Alimera Sciences. "We will continue to work closely with the UK and the Concerned Member States to ensure that Iluvien is made available to patients as soon as possible."
Iluvien is Alimera's sustained release intravitreal implant that releases sub-microgram levels of fluocinolone acetonide (FAc) for up to 36 months for the treatment of chronic DME. The clinical trial data showed that in patients with chronic DME at month 30, after receiving the Iluvien implant, 38 percent of patients experienced an improvement from baseline in their best corrected visual acuity on the Early Treatment of Diabetic Retinopathy Study (ETDRS) eye chart of 15 letters or more. At the completion of the 36-month study, 34 percent had achieved the same result. This effect was highly statistically significant as compared to the sham control group, which received laser and other intravitreally administered therapies.
"Our market research indicates that, given DME is a leading cause of blindness in working-age adults, there is a significant opportunity for an effective ophthalmic drug to treat patients insufficiently responsive to available therapies," said Dave Holland, senior vice president of sales and marketing, Alimera Sciences. "An effective, truly long-term treatment option could have a very positive impact on the quality of life for patients with this chronic debilitating disease."
In July 2010, the Marketing Authorization Application (MAA) was submitted to seven European countries via the DCP with the UK MHRA as the RMS. The MAA included data from two Phase 3 pivotal clinical trials (collectively known as the FAMET Study) for Iluvien conducted by Alimera. The trials involved 956 patients in sites across the United States, Canada, Europe and India to assess the efficacy and safety of Iluvien for the treatment of DME. Based on a consensus arrived upon by the RMS and the CMS, the MHRA issued its Final Assessment Report that Iluvien is approvable.
Safety was assessed among those patients treated with Iluvien who were in the subgroup of patients with DME for three years or more and were considered to have chronic DME. Intraocular pressure (IOP) increases to 30 millimeters of mercury (mmHg) or greater at any time point were seen in 12.7% of these patients by month 36, compared to 18.4% in the full Iluvien treated patient population. By month 36, 3.6% of these patients had undergone an incisional surgical procedure to reduce elevated IOP, compared to 4.8% in the full patient population. The incidence of cataracts among patients with a natural lens in their eye at the start of the study was 84.1% at month 36, with 87.3% undergoing a cataract operation, compared to 81.7% and 80%, respectively, in the full patient population.
pSivida Corp., a leader in developing sustained release, drug delivery products for treatment of back-of-the-eye diseases, today announced the positive outcome of the Decentralized Procedure (DCP) for the approval of Iluvienr in Europe. The announcement follows the issuance of the Final Assessment Report to pSivida's licensee, Alimera Sciences, Inc. from the Reference Member State (RMS), the Medicines and Healthcare products Regulatory Agency of the United Kingdom (MHRA), and the agreement of all the Concerned Member States (CMS) that Iluvien is approvable.
"I'm very pleased about this favorable outcome of the EU regulatory process for Iluvien," said Paul Ashton, president and chief executive officer of pSivida.


One of the toughest tasks in online poker word is to beat the person who has loose aggression. Many people stay in fear while playing with such gamers but actually you can take benefits from their behaviour. Yeah! It is possible to add few potential changes to your playing style so that the aggression less player can soon work like source of earnings. There are five well proven strategies to ensure power full game against least aggressive players.
In case if you have spend long time to get against a drawing hand but are not able to gain benefits then you must be stuck with the bet of loose aggressive player. You might be curious to know details about by what hand he is playing. However, it is possible only if you stay on the same table for significant amount of time. In case if you are playing a multi table type tournament then all players will keep on following different positions for their games and hence you will not be able to crack the game.
Professionals often advise that you must fold hands over cards like King Queen and Ace Ten etc. In case if someone tries to develop pre-flop strategy and you are playing against a lose aggression player then your cards can probably perform well. In case if you have a solid kind of table image then you can prefer to re-raise and he will probably lose the situs poker online game.
Most of the lose aggression players use to bet when actions are in their favour. They are least worried about the win or lose effect so at this moment if you hold a potential card you can easily ensure your win. At that time, other players will try to contact him to check if he is bluffing but this is right moment for you to gain huge amount.
For a while, if we talk about the cash games then it is possible to act before the lose player can do something. You can prefer to take advantage from table. Most of professionals love to play with 'in position' where players can gain information about what others are planning to do before your action. In case if you find yourself locked in front of a lose aggressive kind of agen poker player then it is good to check the premium hands, wait for his bet and then find right moment to raise from your side.
If you are moving towards end of the online poker tournament or probably closer to paid positions or final table then let all other opponents challenge loose player. Even if he has lesser abilities and poor in hand performance but still sometimes they can help to knock down several opponents and your chances of winning gets raised automatically.


I finished the Jumper yesterday!
I am oosing with excitement on how well this guy came out. I'm not sure of a name, but maybe.. Obsession. When I finished him Chris just looked at me and said I was obsessed with the model stuff. Maybe I am, but so what! Maybe it'll make me a profit one day. His right rear leg is a little wobbled. I didn't cut and fill with apoxie, I just heated it up and bent it. I actually bent his face a little too, but it isn't too noticeable with paint on. Well, I have to whip out the sewing machine and get back to POOFs!


Peter Tippett is the chief medical officer for Verizon Enterprise Solutions' health IT practice, the company's practice group that is helping enable the rapidly evolving health care ecosystem through the pragmatic adoption of health information technology. In this capacity, he is responsible for creating Verizon's health care strategy and developing a portfolio of solutions to help transform the delivery of patient care, better manage costs, enhance access to medical services, and provide health data privacy. Tippett also leads the Verizon Innovation Incubator, a group which helps Verizon bring to market new innovative services and technologies.
Previously, Tippett served as vice president of security and industry solutions for Verizon's global enterprise unit, where he led a team of industry experts developing solutions for the energy and utilities, financial services, health care, and retail vertical markets, as well as the company's portfolio of security services.
In his prior role, Peter Tippett was vice president of technology and innovation for Verizon Business. He joined Verizon in 2007 following its acquisition of managed security services leader Cybertrust.
Tippett recently received the U.S. Chamber's First Leadership in Health Care Award for his work to improve transparency and reward innovation through the modernization of the exchange of health information technology. He served on the President's Information Technology Advisory Committee (2003-2005) to guide U.S. efforts in health care IT and information security. In 2002, InfoWorld recognized Tippett as one of the 25 most influential chief technology officers. He also won the Ernst & Young Entrepreneur of the Year award. He was the publisher of Information Security Magazine for its first six years.
Since 1998, Tippett has served as chairman of MD-IT, a rapidly growing health care information technology company.
Tippett has worked as an emergency room doctor and as a helicopter emergency physician and still carries a current California physician and surgeon license.
Tippett, a physician who is board certified in internal medicine, holds a doctorate in biochemistry and an M.D., both from Case Western Reserve University, and a bachelor's degree in biology from Kalamazoo College. To book Technology Speaker Peter Tippett call Executive Speakers Bureau at 800-754-9404.


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Inbox:
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I'm trying to install Freedome for business. After installation, i look into the subscription screen and it shows "initializing" but doesn't go further. It is stuck/frozen.
How can i get the app to proceed with registering the subscription? Can i send a screenshot to you via email?
Were you able to activate your Freedome for Business subscription?
If you are still having any issues, please get in touch with our support team here for further help.


text:
Search for "A Storm of Swords George R.R. Martin"
Tormenta de Espadas / A Storm of Swords
George R.R. Martin: In the House of the Worm
George R. R. Martin and John Jos Miller
A Storm of Swords: A Song of Ice and Fire: Book Three
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Hello big wide world and welcome along to my blog!
So, a little about me and why I decided to start on this little adventure! Well…I suppose you could say that lately I've become a little disillusioned with my current career. Don't get me wrong, it been highly rewarding, enjoyable and enriching but also at times exhausting, frustrating and limiting. 'That's real life!' – I hear you cry! But why should it be that way? I worked hard, studied and developed into the career woman that I thought I wanted to be, but suddenly it felt as though that wasn't enough, it wasn't fulfilling or exciting anymore and for me that meant a change was needed…so, here I am!
I think the spark of inspiration when I met The Canadian last year. After being a 'lone ranger' (read single girl, fabulous life of cosmopolitans, fashion and Netflix *sigh*) for quite a few years it was quite an adjustment suddenly having this other person in my life. Slowly I noticed that his ambition, drive and lust for a life of experience and passion was infectious and was driving me to look further afield. I'd always been a keen traveller, I had been lucky enough to have taken time out from my career to travel the world and always liked to make sure my holidays were ticking off 'The Bucket List', but this was different. We began to make exciting plans for a fabulous future together and before we knew it we were picking up the keys to our beautiful little apartment!
That's when it hit and hit hard! I LOVE interior design. As much as I was excited to be moving in with my other half (although with a sense of trepidation as I'm sure some of you can relate!) I began to wonder, was it wrong that I was also secretly just as excited by the trips to Ikea? By spending hours arranging everything 'just so'? By actually enjoying cleaning, primping and padding around my little space making sure everything looked perfect? I know I'm not alone here…please reassure me! Making our house a home had become my new dedication and Instagram was my obsession. I'd spend hours looking at pictures of exquisitely decorated, beautiful white homes and set out to have mine look just as immaculate yet cosy whilst incorporating my own style. Luckily for me he also adores the Scandinavian and hygge look!
A few months later I started my Instagram page @the.blonde.blog as a little window into my own take on interior design and, well…my life! Straight away felt welcomed by the amazing and supportive community. Within 3 days I had 100 followers and was overwhelmed and overjoyed! The blog came next as a way to keep track of my ramblings and share my journey, my lifestyle and my passion for interiors, fashion, travel and my the wonderful city that I call home – Bristol.
And that's my story, in a nutshell!
So that's it…I hope you'll visit again to find out what I've been up to and hopefully we can find inspiration in each other! Together we can design a life we love!


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GRISLY 'MURDER'
Ukrainian rapper's wife 'who chopped up dead husband's corpse' and kept it in fridge says: 'What have I done?'
Will Stewart
12:31 ET, Aug 1 2020
Updated: 20:19 ET, Aug 1 2020
THE wife of a Russian rapper who confessed to chopping up her husband's corpse pleaded to her lawyer: "What have I done? What have I done?"
Marina Kukhal, 36, has been detained as Russian murder detectives investigate how the singer known as Andy Cartwright, 30 - real name Alexander Yushko - died.
Russian cops are investigating the death of the rapper Andy Cartwright, real name Alexander YushkoCredit: VK.com
Marina Kukhal is said to have confessed to severing her husband's limbs and keeping some body parts in the fridge but it has not been established she killed himCredit: Mash
Parts of Andy's body were kept in black plastic bags in the fridgeCredit: Mash
She confessed to severing his limbs and keeping some body parts in her fridge, but state investigators say they have no proof yet from initial forensic tests that she killed her husband.
Kukhal is being held "for her own protection" from his angry fans, according to one report citing Russian law enforcement.
Investigators fear Cartwright's followers "may take revenge on her for the death of their idol".
She has told police she found the singer dead from a drugs overdose at their elite St Petersburg apartment - and did not want his followers to know he had died such an "inglorious" death.
She aimed to dispose of the rapper's body and then say he had gone missing.
Kukhal has claimed her husband died from a drugs overdoseCredit: RIA FAN
Kukhal told police she had cut up Andy's body over a period of four daysCredit: Social media
There are also reports he had heart problems.
Kukhal claimed he had started taking drugs after becoming depressed during the coronavirus pandemic.
She used a knife, hammer, hacksaw, plastic bowl and chopping board in dismembering him over four days, she told police.
Investigators denied reports attributed to them that some body parts had been cleaned in the family's washing machine.
Yet some human organs including the stomach were reported to be missing from the family flat.
The Russian Investigative Committee it had sought the widow's formal arrest on suspicion of murder despite the lack of concrete evidence.
Kukhal's lawyer Irina Skurtu said: "The remains were kept in Alexander's room (in black bin liners) and in a fridge.
"The smell was only in this room.
"She seemed to me absolutely sane, although very nervous, but she can be understood.
"She does not look to me like a mad drug addict.
"She explained the situation quite coherently, but kept repeating: 'What have I done? What have I done?'"
Kukhal called in her lawyer and the police after realising she "morally" and "psychologically" appalled about her plan to dismember her Ukrainian-born husband's body, said Skurtu.
The lawyer claimed that if she is telling the truth, she has committed no crime in Russian law.
Forensic tests are underway to establish the cause of death.
Investigators fear Cartwright's followers 'may take revenge on her for the death of their idol'Credit: VK.com
Kukhal repeated over and over 'what have I done?'Credit: VK.com
The apartment building at Nevsky Prospekt 134, where the family livedCredit: Google Maps


"Curbside appeal" refers to the first impression that your house makes on potential buyers. Is the front door grungy? Paint it. Are the screens on doors or windows torn? Replace them. Tidy the grounds, porches and garage to hide all clutter from view. If you have a lawn, make sure the grass is trimmed and edged. Not only can curbside appeal make a lasting impression on the buyer; it can affect whether the other real estate agents will return with other clients as well.
The entryway can set the right tone with a trim, attractive door, decorative welcome mat or other thoughtful accent pieces. In spring and summer, consider placing an oversized pot bursting with flowers and greenery near the doorway. In fall or winter consider a tasteful dried wreath to welcome prospective homebuyers.
From the doorway looking into your home, what first draws your eye? Make sure it's eye-catching, whether a piece of artwork, a cozy fire burning in the fireplace or the windows opening to the stunning views beyond.
A clean house is imperative. Make the beds, put away the dishes, tidy the closets and take out the trash. The kitchen and bathroom should shine! (These two rooms can sell a home.) You want to present a home that buyers can imagine themselves moving into the next day.
Lighting helps make a house look spacious show it off to best effect. During the day, leave the curtains open to let in as much natural light as possible, and don't hesitate to leave lights on throughout the house. For evening showings, this is a must! Combining overhead lights with tabletop lamp can create a warm, richly-textured glow. Accent lighting can also draw attention to elements you want to emphasize.
Your home should be free of any odors, whether smoke, pet odors or even strong, chemical smells from cleaning agents.
If have dogs, consider taking them along with you. If not that's not possible, make sure they're secured in the backyard or outdoor pen.
Let the real estate agent do the selling. Your presence can make the buyer nervous and induce them to spend less time - not more - touring your home. Contact me for more information.
When the dust settles, what are the benefits of a home improvement project? See this article.


text:
Browsing the blog archives for January, 2018.
The second half of the season has been a regression back to the mean for the Montis. They've seen their .840 record tumble, mostly on the pitching staff falling back to earth – the 2.25 team ERA mark at the midway point is now 2.45, and the Montis stumbled to an 8-5 record in their first 13 games out of the All-Star Break. Since then however, they've been spectacular, going a spectacular 39-2 (.951) and locking up the division championship in early-August (they stand at 46 games ahead of the second-place Apple Septic Tanks, the only other team in the league above .500).
Alan Wong, Catcher: .321-.372-.613 in 339PA | 8.53 RC/27 | 39HR 99RBI 107R 7SB
Solid as he was in the first half, Wong has kicked things into overdrive, hitting .355-.417-.677 at a consistent clip. Wong was also Daly City's best slugger in the past two months, mashing 18 homeruns to give him 39 on the season, just 4 behind LF Ted Kwong. Interestingly for a hitter of his talents, Wong procured more Runs than RBIs in both months and now stands at 107 Runs to 99 RBIs despite hitting from the #5 spot for most of the season, perhaps an effect of Lew and Kwong clearing the bases ahead of him, and surprising production out of the #6-8 spots. Wong's got a decent shot at the Monti's rookie HR record, needing just 9 more to tie Kwong's record of 48 set last season.
Tina "Experimental ErRR!!" Quach, Backup Catcher: .328-.406-.439 in 471PA | 7.446RC/27 | 6HR 48RBI 71R 9SB
Quach has remained stable for the second half, batting .316-.396-.431 to mostly mirror her season averages as she locks down the C spot in the better defensive alignment that sees her behind the plate, Wong at 3B, and Salgu Wissmath sliding over to SS to take over for the struggling Henry Nghe. At a .406 OBP she's seen her ebb between her normal spot at the bottom of the lineup at the #2 position. With a good last month, she's in striking position of her career-high totals from 2006, needing just 23 more hits, 5 doubles, 1 homerun, 18 RBIs, 13 runs, and 13 walks, in addition to being on pace for a career high across her batting line.
Marco Paz, Backup Catcher: .279-.334-.463 in 164PA | 5.24 RC/27 | 6HR 27RBI 18R 1SB
After one of the most abysmal halves ever to begin the season, many regarded Marco as finished, and indeed his July numbers were also piddling, hitting .286-.310-.357 in 28 at-bats without a single homer. Paz exploded back into form during August however, mashing .373-.449-.644 with 4HR and 15RBIs in his 17 games. While there's not enough playing time left to sniff anywhere close to his 2007 counting totals as a starter, Paz may yet match or even exceed his rate numbers, a remarkable feat given the abysmal first half he had.
Derek Lew, First Baseman: .335-.373-.674 in 619PA | 9.29 RC/27 | 34HR 136RBI 110R 7SB
July saw Derek plunge back to earth, with Lew putting up an anemic .255-.295-.509 line for the month, although he somehow still managed a staggering 25 RBIs out of that. However he jumped right back into form in August, hitting .379-.419-.766 and adding in another 36 RBIs. Overall he's stroked in an incredible 61 RBIs in two months to build up toward 136 on the season – within striking distance of his career high (164 in 2006) and perhaps even the team record (166, by LF Norman Ho in 2004).
Cristian Ortiz, Second Baseman: .315-.370-.578 in 589PA | 8.50 RC/27 | 30HR 103RBI 131R 106SB
Many thought that Ortiz's race for another SB record would be dashed after his two-week stint on the DL from receiving a HBP in May. But undeterred, Ortiz built himself up steadily with 26 steals in 26 July games, and then obliterated records with 31 steals in 28 August games – all on a middling .359 OBP! His wizardry on the basepaths seems to have helped in run production as well – he crossed home plate 67 times (including 37 in August alone). Ortiz also seems to have refound his power stroke, knocking out 17 homers in the past two months. Just 6 steals behind the record 112 he set last year, he's all but set to obliterate that number despite the missed playing time.
Henry "Mr." Nghe, Backup Shortstop: .297-.361-.435 in 267PA | 6.25 RC/27 | 6HR 36RBI 46R 6SB
What once seemed like the start of a new Renaissance may be looked upon as a final swan song in the career of Mr. Nghe, who has hit .262-.297-.328 since July and has been just abysmal unproductive all around. Overall his season numbers still don't look bad, but with the rise of Salgu Wissmath it looks like his days at Daly City's major league level are done.
Salgu "Swissmath" Wissmath, Shortstop: .330-.382-.490 in 482PA | 7.69 RC/27 | 13HR 88RBI 82R 24SB
Wissmath has continued her streak of hot hitting, going .331-.399-.461 in the second half, proving her across-the-board rise in the first half wasn't a fluke. She's batted her way into both a permanent starting spot at SS and oftentimes into the #2 position, an opportunity which might see her eek her way into the 100-100 club (she's at 88 RBIs and 82 Runs currently, having averaged 16 RBIs and 17.5 Runs in the last two months).
Joanna Maung, Saung-gah Basewoman: .163-.255-.184 in 55PA | 1.60 RC/27 | 0HR 3RBI 4R 0SB
Maung's second-half stats are perhaps not even worth mentioning – in 4 games she's managed 12 plate appearances, walking once and going hitless the other 11 times, for a depressing second-half line of .000-.083-.000. Failing to hit at even an A-ball level, it's doubtful Maung may see anymore than a farewell pinch-hit appearance in her last month, and she's liable to see her finish out with perhaps the worst hitting season in Daly City history (her main rival being Marco Paz's .139-.160-.228 in 106 PA's in 2006).
Ted Kwong, Leftfielder: .342-.418-.671 in 610PA | 11.07 RC/27 | 43HR 128RBI 123R 26SB
Lights-out, perhaps the only way that Kwong's numbers can be described. He's hit .360-.420-.707 in the second half, winning the August Batter of the Month award with 13 RBIs and 37 RBIs. He's leading the team in HR by a comfortable amount, although despite the monster numbers he still lags behind 1B Lew in RBI, perhaps a victim of cleaning up behind him. With a decent half-month, he's on pace to best last season's totals in HR, RBI, and hits, although he'll need a continued push to match the gaudy rate stats that won him MVP in 2007.
Tiffany Ho, Centerfielder: .330-.372-.465 in 382PA | 6.39 RC/27 | 6HR 49RBI 52R 6SB
Ho continued on her explosive June as she's continued to make contact and even add a bit of power to her batting – she's hit .353-.404-.516 in the second half. She's taken starts from all around the outfield, especially in Chen's RF absence, but at this point has mostly settled into CF after wresting that away from the soft-hitting Kuo.
Jessica Kuo, Backup Centerfielder: .296-.316-.338 in 370PA | 4.14 RC/27 | 2HR 37RBI 51R 59SB
The speedy CF hasn't batted poorly in the second half, but she's had to fight for playing time with OF Tiffany Ho and saw just 27 games in July and August. Gathering barely any walks or extra base hits, her ability to get on-base and drive in runs has been tied almost purely to her contact, which just hasn't seen the stratospheric heights she achieved in her rookie year. She's managed to maintain her running clip, swiping 20 bags in those 27 games, but she'd need a miracle of playtime and a month for the ages to make up the 31 steals needed to match her career high.
Francis Chen, Rightfielder: .253-.370-.595 in 465PA | 7.99 RC/27 | 36HR 92RBI 86R 16SB
Chen missed a huge amount of games in June and July from his broken finger, but man oh man has he made up for lost time. Despite his absence for the entire first half of July, he leads the team in second-half homeruns, having knocked out 21 (vs Kwong's 20, Wong's 18, Ortiz's 17, and Lew's 13). With a .287-.385-.758 second-half line, Chen is also batting like a complete superstar hitter for the first time in his career.
Skyler Reid, Designated Hitter: .310-.341-.525 in 334PA | 6.68 RC/27 | 13HR 50RBI 48R 0SB
Reid has boomed in the second half of the season, putting up a .359-379-.594 line after a quiet first half to the season, and bringing up his rate stats from the bottom tier of the team back into the middle. He'd do well to insist on staying in his RHP platoon role, where he's hitting .319-.342-.553, as compared to his anemic .271-.338.407 against lefties.
Nathan Yan, #1 Starting Pitcher: .095-.122-.190 in 346+1/3IP | 0.88ERA 0.39WHIP | 37-1 719K 18SHO
The spectacular workhorse season for Yan has continued unabated, recording 5 shutouts out of 8 starts in July, and in his 34th start, breaking the 9-inning strikeout record with 25 K's against the European Cricketeers (it also ties the overall single-game record, set in a marathon 11-inning complete game shutout start on July 1 2006). The increased load doesn't seem to have slowed down Nathan one bit – by mid-August he had registered 34 starts (the number he made last year), having thrown an even 300 innings and a staggering 628 K's, 31 complete games and 16 shutouts, all improvements on his 2007 run.
Whitney Esguerra, #2 Starting Pitcher: .222-.264-.323 in 181IP | 3.03ERA 1.04WHIP 11.4K/9| 16-5 230K 3SHO
The tenacious flamethrower continued a solid if unspectacular second-half, going 6-2 in 74 innings with a 2.92 ERA and notching 5 complete games in that span. She's second on the team in wins, though just barely at 16 over Chin and Vong's 14 in significantly fewer innnings.
Terrence Zhao, Starting Pitcher #3: .209-.288-.296 in 92IP | 1.86 ERA 1.14WHIP 10.0K/9 | 11-0 102K 3SHO
Zhao made his dramatic return from his two-month DL stint with a ruptured tricep tendon, but it looks like it will still take some time to return to his amazing form that saw him throw nearly 4 consecutive May shutouts. He gutted out 3ER on 8+1/3 innings in a win on his return on August 13 against the Mozilla Firefoxes, and just barely made quality starts in his next two outings against the Apple Septic Tanks and US Patriots (3ER on 6+2/3 and 6IP, respectively). Zhao's torrid control issues also persist, having given up a staggering 12 walks in the three starts (5.1 BB/9). Nonetheless, he was a perfect 3-0 in his August return, and remains a 12/12 in quality starts with an 11-0 record.
Samantha Chin, #4 Starting Pitcher: .228-.298-.335 in 168IP | 2.84ERA 1.10WHIP 9.4K/9 | 14-3 176K 2SHO
Chin has been rolling in the second half of the season, despite dropping to the fourth option as a result of Zhao's return. She pitched particularly brilliantly in August, winning 3 of 4 games with a 1.80 ERA and notching her second shutout of the season, an 11-K masterpiece against the European Cricketeers. She's unlikely to reach the lofty heights of her 2007 season, but is on pace to set a career high in strikeouts (33 K's behind).
Alfred Vong, Starting Pitcher #5: .231-.264-.377 in 137IP | 3.22ERA 0.99WHIP 7.4K/9| 14-3 112K 1SHO
Perhaps no one in the rotation has done more with less playing time than Vong this season – he's tied for 3rd on the team in wins with 14 (a career high!) in just 19 starts and 137 innings – far fewer than fellow starters Chin and Esguerra. He finished off the month of August particularly brilliantly, throwing 3 complete games and 1 shutout in 4 starts, recording a 1.85 ERA and 0.71 WHIP in 34 innings.
Sean Wade, Starting Pitcher #6: .272-.318-.396 in 90IP | 5.20ERA 1.29WHIP 7.2K/9 | 7-3 72K 2SHO
The wheels have definitely fallen off the Wade wagon in August, when he notched one of the worst months in Daly City pitching history – 18 ER in 3 starts and 13+2/3 innings, for an 11.85 ERA and 2.05 WHIP. With Zhao's return to fill out the 6-man rotation, Wade may be getting just one or two more starts in to salvage his career.
Kelley Cox, Long Reliever: .228-.302-.350 in 62IP | 2.90ERA 1.26WHIP 7.5K/9 | 5-0 0HLD 0SV 52K
Continuing to fill in for the injured Terrence Zhao, Cox has mostly been held in reserve, making just 5 relief appearances in the second half. She has been nothing short of brilliant in her spot starts however – making her 2nd start of the season on July 24th, throwing a career-high 138 pitches and holding the Asia Giants to a single run in her first ever complete game start, striking out a career-high 9 in the process, and followed that up in an even more brilliant second start – 9 innings, 1ER, and 10 strikeouts in a win. Overall, she's 2-0 with a 1.08 ERA in her 3 starts this season.
Bernadette Dugtong, Middle Reliever: .239-.291-.319 in 36IP | 2.25ERA 1.17WHIP 7.5K/9 | 4-2 6HLD 2SV 30K
Dugtong continues as the most effective rate reliever in the bullpen, amassing a 2.08 ERA in Jul-Aug, although she seems to be losing most of the high-leverage opportunities to Connie Chen, amassing just 9 save opportunities compared to Chen's 25.
Katie Clayton, Setup Reliever: .195-.229-.286 in 22IP | 3.27ERA 0.86WHIP 7.0K/9 | 1-0 17K 6HLD 0SV
Clayton has been a solid part of the bullpen committee, putting up 15 innings in July-August on a 3.00 ERA and 0.87 WHIP. Although she'll have a half-season of limited innings, her performance looks like a career year compared to her first stint with the Montis in 2003-2005.
Connie Chen, Setup Reliever: .259-.326-.386 in 41IP | 3.51ERA 1.39WHIP 6.6K/9 | 2-1 30K 21HLD 1SV
Things have been hot and cold for Chen, who has alternated between spectacular months (1.29, 2.16, and 1.04 ERA's in Apr/Jun/Jul) and complete stinkers (6.23ERA in May and 6.48 in August). Overall she continues a brilliant campaign, and may be considered the team's setup reliever with a staggering 22 holds, already setting a new Montis record (the previous had been just 13, set by Angel Poon in the inaugural 2003 season). She's 2nd in the league in that stat as well, trailing Mozilla Firefox reliever Gary Lawrence by just 1.
Josiah Leong, Closer: .174-.265-.262 in 50IP | 2.16ERA 1.00WHIP 13.0K/9 | 4-2 0HLD 30SV 72K
After a slow start to the saves season (just 13 in the first half), Leong has been a save machine. Josiah picked up a whopping 10 saves in the month of July, including a stretch of 5 appearances and saves on 5 consecutive days from July 19-23. He's now challenging for the league Saves lead, and might have an outside chance of topping his career high of 40, set in his first year as closer in 2004.


text:
Q: Master View Controller -> Detail View Controller Communication Is there a possibility for access to the array defined in Master View Controller from Detail View Controller?
I have a Master-Detail Application in xCode. In Master View Controller an Array is defined. In Detail View Controller there are detail informations according to one entry from this array.
Is it possible to get access from Detail View Controller to the array and update them?
How can I pass the reference to the array from Master to Detail?

A: Is there any link whatsoever between your Master and Detail view?
If so, then you can expose access to the array via making it a "@property" of the Master View Controller that you can access from the Detail view controller.
Here is a related question with answers that may help you out.  I can't give you more specific answers than this because you haven't said how you've set up your Master <-> Detail View Controller implementation.

redpajama_set_name: RedPajamaStackExchange


text:
Name: Dr Catherine Forde
Contact: c.forde@ucc.ie
Academic Unit: School of Applied Social Studies
Dr Catherine Forde is a lecturer in the School of Applied Social Studies, UCC. Her background is in community development and she teaches community development on qualifying undergraduate and postgraduate social work and youth and community work degree programmes. Her main research and publication interests are community development; state-civil society relations; research, teaching and learning in social work education; and children and young people's participation. She is co-author of the books Social Work and Community Development: A Critical Practice Perspective (Palgrave Macmillan, 2015) and Youth and Community Work in Ireland: Critical Perspectives (Blackhall Publishing, 2009).
Community development; sociology; social policy; social work education.
Dr. Forde currently has a HEA/Government of Ireland-funded research project (2018) that has three aims: (i) to identify options for the internationalization and globalization of elements of the social work curriculum in Ireland through engagement between staff of the School of Applied Social Studies, University College Cork (UCC) and the School of Nursing, Midwifery and Social Work, University of Queensland (UQ), Australia (ii) to develop a research and pedagogical relationship between UCC and UQ through the joint development of a digitized module focusing on international and global perspectives on social work practice and (iii) to conduct primary research into Irish social work students' attitudes towards internationalization and globalization of social work both before and after undertaking the new module.
Lynch, D. and Forde, C. (2016) ''Moral Distress' and the Beginning Practitioner: Preparing Social Work Students for Ethical and Moral Challenges in Contemporary Contexts'. Ethics and social welfare, DOI: 10.1080/17496535.2016.1155634.
Forde, C., O'Byrne, D.,O hAdhmaill, F. (2016) 'Community Development in Ireland under Austerity and Local Government Change: Policy and Practice', in C. Forde, D. O'Byrne, R. O'Connor, F. O hAdhmaill, and C. Power (eds.) The Changing Landscape of Local and Community Development in Ireland: Policy and Practice. University College Cork: Institute for Social Sciences in the 21st Century (ISS21).
Forde, C. and Lynch, D. (2015) Social Work and Community Development: A Critical Practice Perspective. Basingstoke, England: Palgrave Macmillan.
Forde, C., Kiely, E., Meade, R. (2009) Youth and Community Work in Ireland: Critical Perspectives. Dublin: Blackhall Press.


If you have finally planned to get rid of your old cathode ray box TV then this post is definitely for you. Long gone are the days when the customary bulky TVs used to rule the show. In modern times, TVs have become lightweight & come in super slim designs with high definition resolution & a vast range of innovative features.
Undoubtedly, LED TVs in Pakistan have made their space in the market owing to their minimal size, efficiency & low power consumption. In the Pakistani home appliances market, you'll come across many options based on screen sizes, features & price but before one goes over LED TV price in Pakistan, one must take into consideration their requirements to juice up their setting.
Being versatile entertainment appliances, they serve best to meet the needs of sports lovers, gamers & as well as for the movie fanatics. Amid such change, we've updated our list of the best Orient LED TVs you can buy online for under 50,000 rupees to help you squeeze every last penny out of your budget so you can afford the important things in life.
So, if you are only willing to put down 50,000 rupees, here are the options you should consider.
Orient's premium 50-inch LED TV lets its users experience a whole new world of splendid realism. The 1920x1080p FHD system of this LED TV demonstrates rich yet natural contrast & amazing clarity to bring true colors of life onto your TV screens.
The Trumpet 40s FHD Black LED TV from the brand's all-time favorite Music Series features a unique design & slim built & offers an amazingly awesome resolution of 1080p to produce dynamic visuals that will literally take anyone's breath away. Incorporating Dolby speakers on the front, this LED TV has the ability to produce rich sound. Offering dozens of innovative features such as screen-sharing, Opera browser, YouTube & Facebook application, the Trumpet is the first choice of users looking for a feature packed yet economical LED TV.
If there's a perfect option for budget consumers then it's definitely Orient's Cougar 32 HD Black LED TV. Owing to the cougar's marvelous colors, powerful Dolby speakers, HDMI/USB connectivity, it serves as a versatile entertainment appliance offering the best of both worlds.
The Orient Tiger is also a great option for those looking for a great LED TV at an economical price. The Tiger's full-color optimizer conveys richer colors all around, along with upholding hue and luminance. Owing to its 720p HD resolution, Orient Tiger delivers crisper visuals with enhanced colors and brilliant brightness. The Tiger's amazingly powerful surround sound speakers enable it to produce multi-dimensional sound to deliver a life-like experience.
The Orient Cheetah 32 HD LED TV owing to its high-quality picture and sound enables users to get the most out of their viewing experience. Offering an operative refresh rate of 50 Hz, 720p HD resolution, premium DTS sound along with modern connectivity options, the Cheetah provides an unmatched entertainment experience. Its sturdy construction makes it a dependable appliance that's destined to serve your entertainment needs for the lifetime.
Whether you are looking to replace your old CTR TV or build your very own home theatre, there is a vast variety of LED TVs available at orient.com.pk to help you make a smart decision.
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Alien – Soundtrack Review
August 19, 2018 August 19, 2018 • Zanobard
Alien is one of the best horror movies ever made, and Jerry Goldsmith's score is most of what makes it such a brilliantly terrifying masterpiece.
Ridley Scott's Alien is an incredible film. The way he perfectly captures terror with just atmosphere is an amazing feat, and this combined with the now legendary alien creature and it's hunt of the poor Nostromo crew makes the movie one of the scariest and certainly most iconic of the horror genre. Jerry Goldsmith's music for the film contributed greatly to this, largely because of it's very thematic, creepy and jumpscare-inducing nature. So without further ado, lets jump into the review.
The album opens with Main Title, which does a wonderful job of introducing the tone and atmosphere (I'm going to be using that word a lot today) of Alien. The music starts out dark and cold, with strings taking the forefront initially. Brass then takes over after a few seconds to play the main Alien theme for the first time. It is a wonderful piece that is at the same time both inspiring and incredibly unnerving. This theme is played for a good two minutes before Goldsmith then moves into much scarier territory with the secondary main theme; a simple two note motif that repeats continuously.
Despite being very simple however it is incredibly effective, as it combined with ominous marching brass in the background easily makes for the most sinister and creepy piece of music on the entire album as well as being the most memorable (the theme is also used repeatedly throughout the entire Alien franchise). It is meant to represent the emptiness of space, and the terrors that could possibly reside within it. It's simplicity is what makes it so unique, and so absolutely terrifying.
Hyper Sleep is up next, and it opens with a few seconds of that shiver-inducing secondary theme. The music starts out slowly before building up its tempo, and just before it ought to move into rapid territory it slows right back down and into a much more peaceful and calm setting. The main Alien theme is played on brass once again with backing strings, but this time in a much more upbeat manner. The marching brass also makes a return, but this time also losing it's creepy edge. All in this makes for a rather unnerving track, as the music that was scary now becomes much more tranquil.
The next track opens in a manner than doesn't sound dissimilar to Star Wars, being very space sci-fi. This doesn't last long however in The Landing as Goldsmith switches up to a short reprise of the main theme and then begins some very sinister sounding strings. The marching brass makes another return here as well as the secondary main theme, but this time they are back to their usual ominous and dark selves. The brass then slowly builds up and gets very loud and menacing towards the end to signify just how much danger the crew of the Nostromo are about to get into.
The Skeleton is very classic-horror-movie style scary, with those rapid violins that are always used in those films making a major appearance. They then fade away after a few seconds and the music takes a rather unusual turn; Goldsmith uses a single echoing note of an instrument (I honestly couldn't say which) on repeat, which like the secondary main theme is very simple yet incredibly disturbing. This is then used a fair amount throughout the rest of the track in combination with the classic sounding violins.
The secondary main theme and it's usual accompaniment of marching brass make another appearance in Nothing To Say, setting a very atmospheric and minacious tone for the next few tracks. This is capitalised mostly in Here Kitty, which marks the first appearance of the theme for the alien creature. The piece is mostly strings based with backing brass, and similarly to the secondary main theme it is quite simple; being just strings that rapidly increase their pitch before moving back down again and repeating. I think it goes without saying now that Goldsmith seems to be a master of simple-but-effective music.
The Shaft is an interesting track, mainly because it is not actually the piece of music used in the ventilation shaft scene in the film. That is actually Desperate Case from another of Jerry Goldsmith's scores; Freud. I can only assume this piece was temp-tracked into the movie and the producers decided to continue using it instead of The Shaft. To be honest, I think this was for the best because it doesn't hold a candle to Desperate Case in terms of how terrifying it was in one of the most tense scenes in Alien. The way the music builds up from just ambient strings to full on terror inducing ones is simply masterful, and it does a great job of illustrating just how horrifying the alien creature is.
Being now well over halfway into the score, it is interesting to note that the music has slowly built up over the course of it's hour long runtime from very atmospheric and slow (but creepy) to fast-paced and downright terrifying. If you insert it into the album instead of The Shaft, Desperate Case does a good job of transitioning between the two different horror styles. This is especially effective considering the music from here on out is mostly the fast-paced scary kind. Parker's Death and Sleepy Alien do a fantastic job of illustrating this, being mainly fast-paced, strings-based and heavily featuring the menacing theme for the alien creature. The score is now very deep into pure horror territory, and because of the superb build-up it is even more effective at sending shivers down your spine.
The score then closes out it's accelerated pace with Out The Door, and moves back into slower and more atmospheric territory with it's End Titles piece. Here the main theme for Alien makes a long and heavily brass-based reprise that ends the score spectacularly. Interestingly however, this track was also not used in the film, being replaced in the end credits by Sinfonia No. 2 by Howard Hanson. This is a choice I do not really agree with, as the Alien theme making one final appearance brings a good sense of closure to the score as well as the film, and so having a track that doesn't belong in the score at all (not even being composed by Goldsmith like Desperate Case) significantly undermines that. Still, we have the proper ending here on the album, and that's what matters.
Overall then, the score to Alien is simply amazing. The main and secondary themes are incredibly atmospheric and in the case of the secondary just downright terrifying. The score as a whole is wondrous and inspiring, and does a fantastic job of representing what horrors could be residing in the depths of deep space. Alien is Jerry Goldsmith's masterpiece, and also one of the most iconic horror scores ever composed. This is why I am awarding it the second Perfect Score of this site. It is very well deserved.
Standout Cue: 1. Main Title
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Crazy Rich Asians – Soundtrack Review
Harry Potter & The Sorcerer's Stone – Soundtrack Review


This destination's lush terrain and close proximity to the mighty Sudety Mountains makes it ideal for Wroclaw Off Road Driving. We've found a great site a short distance from the city centre where your hen can take rugged 4x4s around an off road track peppered with ditches, humps, bumps, trees and surprise water obstacles. Jump behind the wheel and put those driving skills to the ultimate test.
I can go from makeup to mud in 2 seconds flat!
Never driven a 4x4 before? You're in for a white knuckle ride! Few things match the feeling of pure power and unadulterated fun that you get from taking one of these mad machines out for a spin. Instructors who know the Polish countryside inside out and eat, breathe and sleep off road drivin' will show you how to take control of a 4x4 and conquer the seriously tough terrain.
Everyone on the hen do who's up for it will get a turn behind the wheel. Can you make it round the track faster than your friends? Whether you're at the top of the leaderboard or come last, you'll have a brilliant day out and return to the city centre totally buzzed on adrenaline!


The Integrated Reservoir Solutions division of Core Laboratories is offering to interested companies participation in a project designed to optimize operators' exploitation of the liquids-rich, Codell Sandstone in the DJ Basin. This project is a follow-up to our highly successful Niobrara joint industry study.
What is the relationship between the Niobrara hydrocarbon kitchen and the Codell?
What are pay recognition criteria and the appropriate water saturation model for the reservoir and does it change regionally?
These questions can only be solved from the geological, petrophysical and completion/stimulation analysis and evaluation of wells with conventional cores. The resultant data can be used to calibrate open-hole logs in order to better predict rock types and petrophysical properties essential for formation evaluation and proper well completion and stimulation designs. The rock types and their measured petrophysical properties can also serve as analogs when evaluating new reservoirs in wildcats or field step outs.


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Q: Verification Help: Show if $x_n \rightarrow 4$ then $\sqrt{x_n} \rightarrow 2$ I've been struggling to put together limit proofs that hold up, thanks to some previous questions I learned a few things. I hope that this time, I've managed to put together a good proof:
Given $\epsilon > 0, \ \exists N \ s.t. \ \forall n \geq N$ so that:
$|x_n - 4| < \epsilon$
There exists $N_1 \ s.t. \forall n \geq N_1$:
$|x_n - 4| < 1$
$3 < x_n < 5$
$\sqrt{3} < \sqrt{x_n} < \sqrt{5}$ and $\sqrt{x_n}$ is shown to be bounded below by $\sqrt{3}$ for $N_1$
Let $N_* = \max(N_1, N)$, then $\forall n \geq N_*$<
$|x_n - 4| = |\sqrt{x_n} - 2||\sqrt{x_n} + 2|  < \epsilon$
$\epsilon >|\sqrt{x_n} - 2||\sqrt{x_n} + 2| > \sqrt{3}|\sqrt{x_n} - 2|$ and thus
$\sqrt{3}|\sqrt{x_n} - 2| < \epsilon, \ \ |\sqrt{x_n} - 2| < \frac{\epsilon}{\sqrt{3}}$

Much simpler proof given in the comments!

A: In the second-to-last line it looks like you should have $(\sqrt 3 + 2)|\sqrt{x_n} - 2|$ rather than just $\sqrt 3 |\sqrt{x_n} - 2|$.
I would suggest a simplification, however. You observed that $|\sqrt{x_n} - 2||\sqrt{x_n} + 2| = |x_n - 4|$ and this leads right away to $$|\sqrt{x_n} - 2| \le \frac{|x_n - 4|}{2}.$$
So $|x_n - 4| < \epsilon $ implies $|\sqrt{x_n} - 2| < \epsilon$.

A: I think the required proof can have a simpler look.
We suppose that $x_n\ge0$ for all $n$ and that $\lim_{n\to\infty}x_n=4$.
For all $n$, we have :
$$\left|\sqrt{x_n}-2\right|=\frac{\left|x_n-4\right|}{\sqrt{x_n}+2}\le\frac{\left|x_n-4\right|}{2}$$
Consider $\epsilon > 0$.
We know that there exists $N\in\mathbb{N}$ such that $n\ge N\implies\left|x_n-4\right|\le2\epsilon$
Hence, $n\ge N\implies\left|\sqrt{x_n}-2\right|\le\epsilon$
as required.


Situated on more than 60,000 m2 alongside 550 m of private sandy beach, this hotel offers excellent views over the Aegean Sea to the Greek island of Kos. The town of Turgutreis, one of the most beautiful places in the area, is 6 km away, the city centre and airport of Bodrum 24 km and 54 km, respectively. Features of the hotel include 161 rooms, 24-hours reception, currency exchange, TV room, restaurant, 3 bars, outdoor pool, children's pool, mini-club, sports facilities, mini-market and free on-site parking.


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package org.usc.demo.clazz;

import com.google.common.base.Objects;
import com.google.common.cache.CacheBuilder;
import com.google.common.cache.CacheLoader;
import com.google.common.cache.LoadingCache;

import java.util.Arrays;

/**
 *
 * @author Shunli
 */
public class Parent2 {
    private static LoadingCache<CacheKey, String> cache = CacheBuilder.newBuilder().build(new CacheLoader<CacheKey, String>() {
        @Override
        public String load(CacheKey inner) throws Exception {
            System.out.println("Parent2->" + Arrays.toString(inner.getClazz().getDeclaredMethods()));
            return "1";
        }
    });

    public void doAction() throws Exception {
        cache.get(new CacheKey(getClass(), "test"));
    }

    private class CacheKey {
        private Class<?> clazz;
        private String actionName;

        public CacheKey(Class<?> clazz, String actionName) {
            this.clazz = clazz;
            this.actionName = actionName;
        }

        public Class<?> getClazz() {
            return clazz;
        }

        @Override
        public boolean equals(Object obj) {
            if (this == obj) {
                return true;
            }

            if (obj == null || getClass() != obj.getClass()) {
                return false;
            }

            CacheKey other = (CacheKey) obj;
            return Objects.equal(this.clazz, other.clazz) && Objects.equal(this.actionName, other.actionName);
        }

        @Override
        public int hashCode() {
            return Objects.hashCode(clazz, actionName);
        }
    }

}

redpajama_set_name: RedPajamaGithub


text:
Q: CURLOPT_RESOLVE option doesn't work properly with curl php function I'm trying to execute a curl request using CURLOPT_RESOLVE but I get an error :

Warning: curl_setopt() [function.curl-setopt]: Invalid curl
  configuration option

This following line set the option :
curl_setopt($ch, CURLOPT_RESOLVE, 'example.com:443:127.0.0.1');

Any idea what's wrong ?

A: From the php.net doc:

An array of hostname, port, and IP address strings, each element separated by a colon. In the format: array("example.com:80:127.0.0.1")

So you can do that:
curl_setopt($ch, CURLOPT_RESOLVE, ['example.com:443:127.0.0.1']);

A: curl_setopt($ch, CURLOPT_RESOLVE, 'http://example.com:443:127.0.0.1');

A: There is no such option CURLOPT_RESOLVE available which is leading this warning. Please see the list of options on php.net site here


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Natural Rights: A Matter of Origins
An IPS Commentary
By Michael R. Winther, President of the Institute for Principle Studies
Within the general category of "natural rights", there are two underlying schools of thought. Both believe that human beings posses certain rights and that these rights cannot be infringed, even by legitimate government action. (This is not to say that these rights are never violated. In fact, these rights are often infringed by governments acting outside of their proper and legitimate role.) Between these two camps, there is only minor disagreement about what these "natural rights" are, and both camps believe that an understanding of these natural rights is essential to the cause of liberty. Despite all of the commonalities, however, these two schools of thought have one very significant difference: their understanding of the source of these rights.
One might ask, "If both sides generally agree on what these rights are, why does it matter where they come from?" In this article, I will explore some reasons why the source of our rights is an important question—one that needs to be answered.
The difference between the two natural rights philosophies is essentially a religious one. One side, which I will call the "divine rights perspective", sees God as the source of rights and His divinely inspired, written communication as the documentation and clarification of these rights. The other view, which I will call the "atheistic rights perspective", sees rights as innate possessions of all human beings, but does not identify a specific source of these rights. In the atheistic view, rights inure to human beings by virtue of being born human.
There are several logical and philosophical difficulties with the atheistic view of rights and I would like to explore two of them here.
1) The absence of an ethical imperative.
In the "atheist natural rights" worldview, the laws of nature that might relate to our rights become relative instead of absolute. If there is no creator to establish absolute truth, we are left to create our own truths. Human rights, in this scenario, are only pragmatic and cannot have an ethical foundation. If we desire to discover the best philosophical system for laws regarding rights, we would implement various laws and test all of the possible iterations of these laws. Each experiment in rights is a hypothesis to test.
If, through lengthy and detailed study, we determine that a certain philosophy of rights (or set of public laws) produces more productivity, more wealth, or more liberty, society might determine to adopt this set of laws, but there is still no ethical or moral imperative to organize society in that manner. An analogy may be instructive on this point. For example, the laws of physics may allow for many different designs for an automobile. Some of these designs are more efficient than others, but auto makers are free to manufacture vehicles that fall short of the ideal standard that science can produce. Legislators, like automakers, therefore would be free to design laws and formulate rights in various ways, including ways that fall short of the ideal.
2) Competing interests.
Another problem with the atheistic natural rights view is that it must ultimately award rights to those who have superior strength, intellect, or cunning. What does a society do if our legal experimentation concludes that there is no one set of laws that is best for everyone? What if one legal philosophy is best for one group in society and a different legal philosophy is better for another? How would we resolve this conflict? Each group would want the laws that favor them. The answer is simple. The atheist is forced to solve this question of philosophical competition in much the same way that he solves matters of biological competition: survival of the fittest.
In the atheist natural rights model, these political questions must be solved by using a political "survival of the fittest" method, where those with the most political power will dominate those with less power. The end result is that the rights of various minorities are left unprotected.
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Following U.S. Success, Amazon Brings Channels to Europe
By Debra Kaufman
For a year-and-a-half, Amazon has been promoting subscriptions to HBO, Starz and other streaming services. Now, it plans to expand Amazon Channels to Austria, Germany and the U.K. with between 25 to 42 live and on-demand channels from its content partners, thus offering the kind of a la carte TV that many viewers want. Apparently, the success of Channels took Amazon by surprise, and it has created two new channels — Anime Strike and Heera for Bollywood fans — while postponing plans for its own live service. Continue reading Following U.S. Success, Amazon Brings Channels to Europe
Showtime, Starz Now On Tap For Amazon Prime Members
Amazon just began offering some enticing add-ons for its Prime members: on-demand programming from Showtime, Starz and other channels, for as much as $8.99 a month. The goal is to lure more consumers to become Prime members, a $99 a year program that offers unlimited two-day shipping among other benefits, since Prime members spend more money on the site than non-Prime members. The add-on channels can be accessed via Amazon's apps on mobile devices, streaming boxes and connected TVs. Continue reading Showtime, Starz Now On Tap For Amazon Prime Members
Feds Say Time to Prep for Y2Q Quantum Computer Hacking
Twitter Teams with IAS, DoubleVerify to Ensure Brand Safety
NBA Collaboration with Niantic Could Be AR Game Changer
Senators Grill Live Nation on Antitrust After the Swift Debacle
Murdochs Call Off the Proposal to Merge Fox and News Corp
NBA Arena and Avatar Apparel Debut in Meta Horizon Worlds
Microsoft Invests $10 Billion in OpenAI, Valued at About $29B
Disney Announces Plans for Its Proprietary Ad Delivery Stack
TikTok Is Accused of Manually 'Heating' Personalization Feed
Google Taps Page and Brin to Take on ChatGPT for AI Search
Supreme Court Asks DOJ to Weigh In on Online Speech Laws
Tech Firms Push Back as 'Right-to-Repair' Gains Momentum
Reed Hastings Transitioning to Executive Chairman of Netflix
New Ad Certification Group Seeks Support of Major Agencies
Apple Debuts MacBook Pros with M2 Pro and M2 Max Chips
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How Robots Revolutionised Watchmaking
The use of robotics within watchmaking is not new; Seiko Epson has been using robots on its production lines since the early 1980s, however, there has been a recent surge in furthering the use of robotics in this field.
The likes of Percipio's Chronogrip robot, designed to facilitate micromanipulation, can manoeuvre and assemble mechanical parts ranging from a few millimetres to a few thousandths of millimetres in size.
Currently the Chronogrip robot cannot work autonomously, instead of needing a human to operate it. David Heriban, Percipio CEO, tells Atelier.net: "The idea behind Chronogrip is to be extremely precise, to help the person concerned to assemble the components."
The Chronogrip, and other watchmaking robots are enabling manufacturers to produce quality timepieces in smaller timeframes than before.
Pierre-André Bühler, of the Swatch management board, says:
"Before, we worked with 55 different machines. Now, with our five high-tech production lines, we can manage with a minimum number of employees, whose job it is to assist the robots, take charge of production and develop software, so we can reduce production times enormously."
Watch this video from Epson to see how watchmaking robotics have evolved since 1942.
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