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After hiking my boots to shreds, I contacted LOWA in Germany about getting a new pair of my favorite shoes evah. Since the style is now long outdated, out of stock and I couldn't get another pair, they offered to replace the soles of the old ones at no cost. Suhweet! Nach dem Wandern meine Stiefel zu Fetzen, kontaktierte ich LOWA in Deutschland darum, ein neues Paar meiner Lieblings-Schuhe evah. Da der Stil ist heute langst veraltet und vergriffen und ich konnte nicht ein anderes Paar, boten sie die Sohlen an keinen Kosten zu ersetzen. Suhweet!


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The early versions of the Backplane

Most people focus on the solutions instead of identifying the problems people want solved. Make sure to work backwards from the needs of your potential customers (including yourself).

Convincing people it will work before they buy was solved with video and testimonials. Some folks also have an issue with my product not being made of fancy materials. I'm more of a guy that cares if something works. To keep my costs down, I keep things simple.

Your product will NEVER be perfect. Focus on finding people who want it and then you can evolve your product to be better over time. Think about the first generation iPod vs the current iPhone 5s!

Practicing failure was key to persevering with this product. It's a turning point. I remember the first time watching Shark Tank after successfully pre-selling my product. I was yelling at the contestants "What do you mean, you are PRE-REVENUE? You have HOW MUCH inventory? 2800 … ARE YOU CRAZY!? HOW WILL YOU SELL THAT?"

Fear of failure is one of the most non-talked about issues people face when starting a business. Practicing failing in your business and personal life will help you overcome the fear of failure. Check out or woven tassel sliders Find Great Sale Online Sale Classic Buy Cheap Collections Best 56Pzh

I had to get over my need for things to be perfect. I have iterated with customers, especially when it comes to something as variable as posture for individual humans. My current design is the result of 27 prototype iterations . I've also learned to politely ignore people who immediately start giving me advice on how to SCALE, when 99% of those people haven't ever made a single dollar on a product themselves.

First, get a customer base. Early interaction with customers is key to ensuring you have a great product and you address the most common concerns. An ecommerce solution should help withthe problem of having too many customers to fulfill manually. Once you have that problem, make it as easy as possible for people to buy.

I'm up to about $1000 in revenue, with zero investment of my own money. Read that last sentence again, ZERO.

Enter Dan Maisano of EasyWhey, who started his own protein drink to-go product.

I read Tim Ferriss' book Four Hour Workweek and the idea of a "Muse" type business appealed to me. I decided to create "Dan's Super Convenient and Awesome Protein" shake because I drink whey protein on a regular basis but it has never been the most convenient thing to do.

As one of the healthier snacks/meals out there it would be great to be able to drink it anytime. Breakfast, lunch, afternoon snacks, traveling, car trips, movies etc. I know many people who use the shakers that lets them scoop in their own whey, add water or milk and drink. To me this was never convenient.

A person had to then carry the shaker around with them, make sure they clean it ASAP (if you ever have smelled an old protein shaker you know why) and just plan to have it with them until they are able to get home. I personally wanted something that I could drink when I wanted and then forget about it.

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Parkinson’s resting tremor is related to altered cerebral activity in the basal ganglia and the cerebello-thalamo-cortical circuit. Although Parkinson’s disease is characterized by dopamine depletion in the basal ganglia, the dopaminergic basis of resting tremor remains unclear: dopaminergic medication reduces tremor in some patients, but many patients have a dopamine-resistant tremor. Using pharmacological functional magnetic resonance imaging, we test how a dopaminergic intervention influences the cerebral circuit involved in Parkinson’s tremor. From a sample of 40 patients with Parkinson’s disease, we selected 15 patients with a clearly tremor-dominant phenotype. We compared tremor-related activity and effective connectivity (using combined electromyography-functional magnetic resonance imaging) on two occasions: ON and OFF dopaminergic medication. Building on a recently developed cerebral model of Parkinson’s tremor, we tested the effect of dopamine on cerebral activity associated with the onset of tremor episodes (in the basal ganglia) and with tremor amplitude (in the cerebello-thalamo-cortical circuit). Dopaminergic medication reduced clinical resting tremor scores (mean 28%, range −12 to 68%). Furthermore, dopaminergic medication reduced tremor onset-related activity in the globus pallidus and tremor amplitude-related activity in the thalamic ventral intermediate nucleus. Network analyses using dynamic causal modelling showed that dopamine directly increased self-inhibition of the ventral intermediate nucleus, rather than indirectly influencing the cerebello-thalamo-cortical circuit through the basal ganglia. Crucially, the magnitude of thalamic self-inhibition predicted the clinical dopamine response of tremor. Dopamine reduces resting tremor by potentiating inhibitory mechanisms in a cerebellar nucleus of the thalamus (ventral intermediate nucleus). This suggests that altered dopaminergic projections to the cerebello-thalamo-cortical circuit have a role in Parkinson’s tremor.

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Parkinson’s disease is a progressive neurodegenerative disorder characterized by bradykinesia, rigidity and a 4–6 Hz resting tremor. The pathological hallmark of Parkinson’s disease is nigro-striatal dopamine depletion ( Kish et al. , 1988 ). However, in contrast to bradykinesia and rigidity, the relation between tremor and dopamine (depletion) is unclear. For example, the response of tremor to dopaminergic medication varies greatly between patients, with some patients exhibiting a remarkable dopamine-resistant tremor ( Pogarell et al. , 2002 ; Fishman, 2008 ). Furthermore, unlike other motor symptoms, tremor does not correlate with striatal dopamine depletion ( Pirker, 2003 ). Instead, it has been suggested that resting tremor is linked to pallidal dopamine depletion ( Mounayar et al. , 2007 ; Helmich et al. , 2011 ) or to abnormalities in the noradrenergic ( Isaias et al. , 2011 ) and serotonergic systems ( Doder et al. , 2003 ; Qamhawi et al. , 2015 ). Here we aimed to resolve these discrepancies by investigating the cerebral mechanisms underlying the effect of dopaminergic medication on resting tremor in patients with Parkinson’s disease.

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Fig. 2

Top: Bland–Altman plots comparing the photographic portion guide and the plated reference portion responses to estimate ‘typical’ participant intake mass (oz) for fish and shrimp. The 95 % CI of the limits of agreement (dashed lines indicating ±2 sd of the mean difference) estimates the magnitude of possible sampling error. The mean difference (solid lines) for the two methods indicates sampling bias; the 95 % CI of the mean difference includes the line of equality (zero) for fish data, but not for shrimp data. Bottom: Distribution plots of differences between participant selections from the photographic portion guide and their plated reference portion. Histograms, supported by goodness-of-fit, indicated fish and shrimp data had a normal distribution

Gender, age and racial characteristics of the study participants: adults aged 25–64 years, south-eastern USA

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Data presented are the numbers of participants in each demographic category.

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The present study validated the utility of a photographic guide for assessing typical portion sizes for fish and shrimp consumed by adults. Data accuracy in the study was comparable to or better than that of other reports using photographs for estimating food portions ( 23 25 ) . Accuracy in assessing fish and shellfish intake is required to discern how seafood consumption can impact health benefits as well as health risks associated with environmental disasters and contaminants ( 26 28 ) .

Forty-six per cent of respondents in the fish study, and 48 % of respondents in the shrimp study, accurately represented their plated reference portion using the photographic portion guide. Ninety-three per cent of respondents in the fish study, and 91 % of respondents in the shrimp study, represented their plated reference portion ±2 oz (±56·7 g) using the photographic portion guide. Data from both fish and shrimp studies showed positive correlation between the two methods for both fish and shrimp estimates. Such descriptive statistics, however, do not address agreement between the two methods. Bland–Altman plot analyses address potential bias between the mean differences for the two evaluation methods and provide an estimate for an agreement interval, within which 95 % of the differences of the photographic portion guide, compared with the plated reference portions, fall ( 29 ) . These differences ultimately provided acceptable agreement between the two methods from a practical standpoint. Bias in both the fish and shrimp studies was less than 1 oz (28·3 g; Fig. 2 ). Nevertheless, the 95 % CI for mean differences in shrimp study data (+0·77 oz (+21·8 g)) indicated a systematic difference between the methods, indicating a subtraction correction of 0·77 oz (21·8 g) from shrimp portion guide estimates would be expected to provide data more comparable to the ‘gold standard’ plated reference portions. Bias observed in both studies did not appear associated with low v . high portion size preferences.

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