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Bottled-water consumption in the U.S. hit 39.3 gallons per capita, according to recent data, while carbonated soft drinks fell to 38.5 gallons, marking the first time that soda was knocked off the top spot, Novica Silver beaded wristband bracelet Misty Grey uVaRtKcNu
. But soda is still more expensive, racking up $39.5 billion in sales versus $21.3 billion for water, industry research group Euromonitor found. “In 2016, bottled water overtook carbonates to become the leading soft drinks category in off-trade volume terms, an astonishing milestone a decade in the making,” it said.

While the fizzy soda category has experienced an annual volume sales decline since 2003, bottled water grew every year over the last two decades, except 2009 during the depths of the Great Recession, driven by consumer concerns about the effects of artificial sweeteners and sugar. But some commentators say people should avoid all three.

The margins on bottled water are huge. Case in point: Nestlé NESN, +0.28% makes billions bottling water it pays nearly nothing for, Bloomberg reported in September . Apart from transportation, infrastructure and salaries, “Nestlé pays little for the product it bottles — sometimes a municipal rate and other times just a nominal extraction fee,” the Bloomberg report said. “In Michigan, it’s $200.”

Nestlé said it’s have invested about $270 million in infrastructure Michigan, and other expenses related to the sustainability of resources in that state. “This includes the scientists, engineers, biologists and others who work for our company,” it said. “Rainfall and snowmelt recharges the aquifer every year at a rate higher than our proposed withdrawal, meaning that we are taking out less than what nature is putting back in.”

The company is not alone in producing cheap bottled water at, some experts say, the expense of local water utilities. Bottled water is often sourced from the municipal water supply.

Bottled water has surged more than 2,700% in four decades

More than one-quarter of bottled water revenue last year was shared by the soda giants Coca-Cola Co. KO, +0.55% and PepsiCo PEP, -0.67% which sell Dasani and Aquafina respectively. In the four decades since the launch of Perrier water in the U.S., consumption of bottled water surged 2,700%, from 354 million gallons in 1976 to 11.7 billion gallons in 2015, according to the International Bottled Water Association.

And not all European bottled water is always free of chemicals, according to studies of European bottled waters carried out in Germany, Switzerland, Italy and France — one published in 2011 and the other in 2013 — by the Goethe University Frankfurt’s Department of Aquatic Ecotoxicology. Among the main compounds Wagner found: Endocrine disrupting chemicals, or EDCs, which can act like hormones in the body and have been linked to diabetes, breast cancer and cardiovascular disease. (Representatives from the bottled water industry contend that the origin of these EDCs were likely environmental rather than from a packaging material.)

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Analysis of 589,306 genomes identifies individuals resilient to severe Mendelian childhood diseases

Article | Published:

, pages 531 538 (2016) | 1928 Jewelry 1928 Vintage Inspirations Womens Purple Stretch Bracelet KhknAPBD

Genetic studies of human disease have traditionally focused on the detection of disease-causing mutations in afflicted individuals. Here we describe a complementary approach that seeks to identify healthy individuals resilient to highly penetrant forms of genetic childhood disorders. A comprehensive screen of 874 genes in 589,306 genomes led to the identification of 13 adults harboring mutations for 8 severe Mendelian conditions, with no reported clinical manifestation of the indicated disease. Our findings demonstrate the promise of broadening genetic studies to systematically search for well individuals who are buffering the effects of rare, highly penetrant, deleterious mutations. They also indicate that incomplete penetrance for Mendelian diseases is likely more common than previously believed. The identification of resilient individuals may provide a first step toward uncovering protective genetic variants that could help elucidate the mechanisms of Mendelian diseases and new therapeutic strategies.

Advances in genomic technologies have rapidly expanded our knowledge of the genetic basis of human disease. To date, >6,000 Mendelian disorders have been described (Online Mendelian Inheritance in Man (OMIM)), with more than 150,000 disease-associated variants identified across these disorders in the Human Gene Mutation Database (HGMD). Despite the success of genome-wide association and whole-exome and whole-genome sequencing (WES/WGS) studies in revealing the DNA variants that underlie the genetic basis of disease, the development of effective treatments for most diseases has remained a challenge. Even for Mendelian disorders, only a handful of drugs have been developed. One reason for this lack of success is the difficulty of using small-molecule therapies to restore protein activity in the presence of loss-of-function (LoF) mutations. As a result, treatment of Mendelian disorders typically focuses on the relief of symptoms rather than on a biological 'cure'.

A promising avenue for addressing some of these limitations is to focus analysis on the genetic and environmental modulators that keep people well by suppressing the effects of disease-causing mutations. However, a major challenge in identifying resilient individuals is accurately cataloging disease mutations. Currently, there are no databases that provide a complete characterization of disease genes and their mutations as well as in-depth clinical annotations. For example, the OMIM database contains all known Mendelian disorders with detailed clinical characterizations, but has limited descriptions of disease-causing mutations. In contrast, HGMD has collected almost all disease-associated variants reported to date, but has almost no parameters pertaining to the clinical characteristics attributed to these variants. Furthermore, although many commercial pan-ethnic screening panels cover the most common highly penetrant mutations, important mutations might be omitted owing to technological limitations and cost-benefit considerations. Also, the exact mutations in these commercial pan-ethnic screening panels are typically inaccessible to the public.

Despite these challenges, identification of secondary modulators has proven successful across a multitude of model organisms in which the prominent role of second-site suppressors that buffer or modify traits has been established. For example, human genetic studies have identified rare mutations in that confer resilience against HIV infection, mutations in globin genes that modify the severity of sickle cell disease by buffering primary mutations in β-globin genes, and LoF mutations in that protect carriers from high lipid levels and resulting heart disease. Second-site mutations in disease genes have also been shown to revert clinical phenotype in patients with recessive dystrophic epidermolysis and Fanconi anemia, whereas LoF mutations in zinc transporter 8 have been found to protect obese individuals from diabetes. Most recently, a variant identified in the gene was found to confer resilience to Duchenne muscular dystrophy in two dogs, implicating as a therapeutic target for the disorder.

Here we analyze sequence and genotype data from 589,306 individuals across 12 studies (complete list in Online Novica Silver beaded cord bracelet Affinity in Gray kHnrOitS
) to identify healthy individuals harboring what are currently believed to be completely penetrant Mendelian disease-causing mutations. We refer to this search for resilient individuals as the Resilience Project. We screen mutations in 874 genes believed to cause 584 distinct severe Mendelian childhood disorders. In total, we identified 13 candidate resilient individuals spanning 8 diseases. The genomes of such resilient individuals, if appropriately decoded, hold promise in elucidating protective mechanisms of disease that could lead to novel treatments.

We carried out a search of existing genomic data for individuals who may be resilient to disease by focusing on mutations annotated as being completely penetrant for severe childhood Mendelian disorders. Our rationale for restricting attention to these disorders is manifold. First, there is a significant unmet medical need for many of these disorders that have the potential to benefit from the identification of resilient individuals. Second, a focus on diseases with a more profound phenotype and a simple genetic architecture decreased the chances of diagnostic errors or missed diagnoses due to subclinical manifestation of disease. This is particularly important for our screen, given we generally did not have access to medical records and depended on self-reporting of conditions by study participants. Finally, restricting attention to severe childhood disorders and including only individuals over the age of 18 reduces the likelihood that subjects harboring deleterious mutations will manifest the disorder later in life. The overall workflow for the retrospective search for resilient individuals is depicted in Figure 1 .

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