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The science of studying diamond inclusions for understanding Earth history has developed significantly over the past decades, with new instrumentation and techniques applied to diamond sample archives revealing the stories contained within diamond inclusions. This chapter reviews what diamonds can tell us about the deep carbon cycle over the course of Earth’s history. It reviews how the geochemistry of diamonds and their inclusions inform us about the deep carbon cycle, the origin of the diamonds in Earth’s mantle, and the evolution of diamonds through time.
Let M be a smooth compact manifold with boundary. Under some geometric conditions on M, a homotopical model for the pair (M, ∂M) can be recovered from the configuration category of M \ ∂M. The grouplike monoid of derived homotopy automorphisms of the configuration category of M \ ∂M then acts on the homotopical model of (M, ∂M). That action is compatible with a better known homotopical action of the homeomorphism group of M \ ∂M on (M, ∂M).
INTRODUCTION: FROM EDMAN SEQUENCING TO MASS SPECTROMETRY
Prior to mass spectrometry, E dman degradation was the only technique to obtain the sequence information of proteins. Edman sequencing was based on the chemical reaction of the N-terminal amine with phenyl isothiocyanate, leading to a phenylthiocarbamoyl derivative, which was cleaved upon acidification and determined based on chromatography or electrophoresis. This was a slow process identifying one amino acid per reaction cycle. In addition, it required that the N-terminus of the proteins of interest was not blocked. However, most intact proteins, if they are not processed from a secretory or pro-peptide form, are blocked at the N-terminus, most commonly with an acetyl group. Other amino-terminal blocking includes fatty acylation, such as myristoylation or palmitoylation. Cyclisation of glutamine to a pyroglutamyl residue and other post-translational modification to N-termini also occur. In short, all these modifications leave the N-terminal residue without a free proton on the alpha nitrogen, thus Edman chemistry cannot proceed. Nowadays, Edman sequencing plays a minor role in protein analyses and has been surpassed by biological mass spectrometry techniques.
This revolution of biological mass spectrometry was largely enabled by the soft ionisation techniques ESI and MALDI (see Sections 15.2.4 and 15.2.5) that allowed the largescale analysis of biomolecules (proteins, peptides, oligonucleotides, oligosaccharides and lipids) and thereby revolutionised the areas of proteomics and metabolomics (Chapter 22). In contrast to electron impact (EI), these soft ionisation techniques produce molecular ions and only insignificant amounts of fragment ions. Therefore, in order to obtain structural sequence information on biomolecules, tandem MS (or MS/ MS) has been developed. Furthermore, the faster speed and sensitivity of tandem MS soon dwarfed the sequencing turnaround available by Edman degradation.
The identification of proteins by mass spectrometry usually involves protease cleavage, mostly by trypsin. Owing to the specificity of this protease, tryptic peptides usually have basic groups at the N- and C-termini. Trypsin cleaves after lysine and arginine residues, both of which have basic side chains (an amino and a guanidino group, respectively). This results in a large proportion of high-energy doubly charged positive ions that are easily fragmented. The digestion of the protein into peptides is followed by identification of the peptides by tandem mass spectrometry (Section 21.3). This is commonly referred to as bottom-up or shotgun proteomics.
Background: Little knowledge exists on the availability of academic and community paediatric neurology positions. This knowledge is crucial for making workforce decisions. Our study aimed to: 1) obtain information regarding the availability of positions for paediatric neurologists in academic centres; 2) survey paediatric neurology trainees regarding their perceptions of employment issues and career plans; 3) survey practicing community paediatric neurologists 4) convene a group of paediatric neurologists to develop consensus regarding how to address these workforce issues. Methods: Surveys addressing workforce issues regarding paediatric neurology in Canada were sent to: 1) all paediatric neurology program directors in Canada (n=9) who then solicited information from division heads and from paediatric neurologists in surrounding areas; 2) paediatric neurology trainees in Canada (n=57) and; 3) community paediatric neurologists (n=27). A meeting was held with relevant stakeholders to develop a consensus on how to approach employment issues. Results: The response rate was 100% from program directors, 57.9% from residents and 44% from community paediatric neurologists. We found that the number of projected positions in academic paediatric neurology is fewer than the number of paediatric neurologists that are being trained over the next five to ten years, despite a clinical need for paediatric neurologists. Paediatric neurology residents are concerned about job availability and desire more career counselling. Conclusions: There is a current and projected clinical demand for paediatric neurologists despite a lack of academic positions. Training programs should focus on community neurology as a viable career option.
Bloodstream infection (BSI) due to methicillin-resistant Staphylococcus aureus (MRSA) is associated with considerable morbidity and mortality.
To determine the incidence of MRSA BSI in Canadian hospitals and to identify variables associated with increased mortality.
Prospective surveillance for MRSA BSI conducted in 53 Canadian hospitals from January 1, 2008, through December 31, 2012. Thirty-day all-cause mortality was determined, and logistic regression analysis was used to identify variables associated with mortality.
A total of 1,753 patients with MRSA BSI were identified (incidence, 0.45 per 1,000 admissions). The most common sites presumed to be the source of infection were skin/soft tissue (26.6%) and an intravascular catheter (22.0%). The most common spa types causing MRSA BSI were t002 (USA100/800; 55%) and t008 (USA300; 29%). Thirty-day all-cause mortality was 23.8%. Mortality was associated with increasing age (odds ratio, 1.03 per year [95% CI, 1.02–1.04]), the presence of pleuropulmonary infection (2.3 [1.4–3.7]), transfer to an intensive care unit (3.2 [2.1–5.0]), and failure to receive appropriate antimicrobial therapy within 24 hours of MRSA identification (3.2 [2.1–5.0]); a skin/soft-tissue source of BSI was associated with decreased mortality (0.5 [0.3–0.9]). MRSA genotype and reduced susceptibility to vancomycin were not associated with risk of death.
This study provides additional insight into the relative impact of various host and microbial factors associated with mortality in patients with MRSA BSI. The results emphasize the importance of ensuring timely receipt of appropriate antimicrobial agents to reduce the risk of an adverse outcome.
Infect. Control Hosp. Epidemiol. 2016;37(4):390–397
This research sought (a) to investigate the similarities and differences in how pharmaceutical services are provided by community pharmacies (CPs) and dispensing doctor practices (DPs) and (b) to identify the issues relevant to determining the quality of pharmaceutical services in these settings.
UK pharmaceutical services, including dispensing prescriptions and public health advice, can be provided from both (CP) and, in rural areas, (DP). While there is much similarity between CPs and DPs in the types of services provided, there is also the potential for variation in service quality across settings.
A postal questionnaire of DPs and CPs in South West England was conducted to provide a descriptive overview of pharmaceutical services across the settings. A subsection of questionnaire respondent sites were selected to take part in case studies, which involved documentary analyses, observation and staff interviews.
Survey response was 39% for CPs (52/134) and 48% (31/64) for DPs. There were three CP and four DP case study sites, with 17 staff interviews. More pharmacies than practices were open at the weekend and they had more staff trained above NVQ level 2. Both doctors and pharmacists saw themselves as medicines experts, as being accessible and having good relationships with patients. Workplace practices and organisational ethos varied both within and across settings, with good practice observed in both. Overall, CPs and DPs have much in common. Workplace culture and an evidence-based approach to checking prescriptions and error reporting need to be considered in future assessments of service quality.
Photo-actuating structures inspired by the chemical sensing and signal transmission observed in sun-tracking leaves have recently been proposed by Dicker et al. The proposed light tracking structures are complex, multicomponent material systems, principally composed of a reversible photoacid or base, combined with a pH responsive hydrogel actuator. New modelling and characterization approaches for pH responsive hydrogels are presented in order to facilitate the development of the proposed structures. The model employs Donnan equilibrium for the prediction of hydrogel swelling in systems where the pH change is a variable resulting from the equilibrium interaction of all free and fixed (hydrogel) species. The model allows for the fast analysis of a variety of combinations of material parameters, allowing for the design space for the proposed photo-actuating structures to be quickly established. In addition, experimental examination of the swelling of a polyether-based polyurethane and poly(acrylic acid) interpenetrating network hydrogel is presented. The experiment involves simultaneously performing a titration of the hydrogel, and undertaking digital image correlation (DIC) to determine the hydrogel’s state of swelling. DIC allows for the recording of the hydrogel’s state of swelling with previously unattained levels of resolution. Experimental results provide both model material properties, and a means for model validation.
In 1998, after 21 years with the Economic Research Service of the U.S. Department of Agriculture, I left government service to begin the next, and current, chapter of my mathematical career.
I look back with amazement at the fact that, although I was employed by an agency devoted to agricultural economics rather than mathematics, not once was I assigned a subject area in which I couldn't find interesting and enjoyable mathematical content. Federal government agencies seem to provide researchers more freedom than the private sector to choose projects or to steer assignments in a compatible direction. In this sense, federal government employment perhaps occupies a middle ground between academic and private-sector employment.
My experience over the years has convinced me that mathematics can be found wherever you look. For example, when I was working in a research group on food-safety economics, I noticed that a probability theoretic argument could be used to show that larger fast-food chains stand to lose not merely more revenue from foodborne disease incidents, but a higher percentage of their revenue. This finding was reported in the food industry press. In another study, I drew on generalized central limit theorems to evaluate safety data on heat-treated meat patties. My conclusions—in disguised form—actually found their way into the Congressional Record.
In business, you don’t get what you deserve, you get what you negotiate.
Chester L. Karrass
You must never try to make all the money that’s in a deal. Let the other fellow make some money too, because if you have a reputation for always making all the money, you won’t have many deals.
J. Paul Getty
The fellow who says he’ll meet you halfway, usually thinks he’s standing on the dividing line.
Orlando A. Battista
Like it or not, you often will be negotiating something in life, and always will be negotiating something in an entrepreneurial pursuit. The negotiation could be direct or indirect, obvious or subtle, but as an entrepreneur, you always will be negotiating.
As just one example, my colleague Michael (first author of this text) shared with me a very important lesson in this regard from one of the angel investors that was his first major outside investor, Peter. Peter was seventy-one years old when he first became involved in my friend’s commercial fish farming company. He was the master at just about everything to do with starting a new business. Peter had left a Big 4 accounting firm (probably was the Big 8 back then) to launch his entrepreneurial career, when he had four children and a wife to support at the time. Among other deal points, Peter negotiated with Michael to purchase a 20% equity stake in his company in exchange for Peter’s cash investment. Michael violated a soon-to-be-learned rule, one that Peter was about to teach him the hard way. Peter had originally agreed to invest in the company for 18%, but later simply said that he’d feel a lot better if my friend could “round up” this figure to 20%. It wasn’t necessary, but it would be “nice.” Wanting to get the deal done, given that the parties were so close, and concerned he might otherwise disappoint or aggravate Peter, Michael said, “OK.” Michael didn’t ask what he would get for bumping up Peter’s equity stake or say something such as, “I’ll do that for you if you do XYZ in return.” Peter later told Michael that this was part of the negotiation, not simply a casual request.
People are definitely a company’s greatest asset. It doesn’t make any difference whether the product is cars or cosmetics. A company is only as good as the people it keeps.
Mary Kay Ash (1915–2001; U.S. Business Executive)
You’re making great progress. You’ve got a board, you are about to hire two key employees, and you are just about ready to start executing your company business strategy. But, you need a company structure to embody these attributes. In fact, you can’t even open a bank account without an Employer’s Identification Number (EIN). This is no simple decision. In particular, your board (typically made up of “older” types) will probably steer you in the direction of a conventional commercial corporation, aka C-Corp. Why, because they are familiar with it. People just about always think what they are familiar with is best, else why would they have been doing it all these years? I believe that a limited liability corporation (LLC) is probably your best bet at this point of your company history for a variety of reasons we discuss in this chapter. I’m not a lawyer, and this is where you should seek legal advice once you think you know what you want to do. In fact, never go to a lawyer and ask them an open-ended question such as “What should I do?” They will just about always guide you in the most conservative direction legally, and this may not be best for your company.
Types of Ownership Structures
Before you can decide on an ownership structure for your business, you should learn a little bit about how each structure works. As a good reference on deciding which ownership structure is most suitable for your business, read “Choosing the Best Ownership Structure for Your Business” (go to www.nolo.com/lawcenter).
I have no use for bodyguards, but I have very specific use for two highly trained certified public accountants.
It seems as if addition, subtraction, multiplication, and division should be fairly simple. It is, until you want to apply it to accounting and do your tax calculations! There are many ramifications resulting from your choice of corporate structure on how you end up paying taxes. For example, who in their right mind would choose to pay taxes twice on profits you make from your company? Well, if you choose a C-Corp for your company structure, that’s just what you’ll be doing! But sometimes a C-Corp is the best choice, and you might ask why. I think my accountant was probably the key professional with whom I interacted with during the early days of my start-up. I recommend seeking an accountant’s advice early, before you create your company structure.
At this point in the text, we’ve covered the basic steps of defining your business, developing a marketing strategy, and differentiating your business from the competition. In this chapter, we cover the creation and use of financial accounting statements in the typical business plan, including depreciation and taxation issues. We stress the importance of creating these financial statements from the top down versus the bottom up by basing the figures on details from the demand side of the equation, that is, sales and the costs of production.