Some lines...should not be crossed. And yet, what if they are? When does love end, where does it begin? Is death an end, a means to an end, or just the next step on the journey? Friendship and loss, desire and fear. Aliens, droids, demons, humans, and life. How far will they go and what will happen if they do? This collection of seventeen stories edited by Seth Crossman raises the bar for speculative fiction. With stories by Sara Genge, Joe Vadalma, Jakob Drud, Barton Paul Levenson, Steven Mathes, Timalyne Frazier, James Steimle, L. Christopher DelGuercio, Greg Schwartz, Bosley Gravel, Lori Strongin, Michael Savastano, Manfred Gabriel, Rachel Astruc, Berrien Henderson, Lindsey Duncan and Michael Davis it is sure to please any fan of speculative fiction. Bruce Golden, author of Better Than Chocolate, called Forbidden Speculation "a robust and imaginative collection of mind-bending tales.
Modern space adventures crafted by a new generation of Grand Tradition science fiction writers. Smart, engaging stories that take us back to a time when science fiction was fun and informative, pithy and piquant-when speculative fiction transported us from the everyday grind and left us wondrously satisfied. Showcasing the breadth of Grand Tradition stories, from 1940s-style pulp to realistic hard SF, from noir and horror to SF spaceships, alien uplift, and action-adventure motifs, Far Orbit's diversity of Grand Tradition stories makes it easy for every SF fan to find a favorite.
This book deals in general with mergers & acquisitions in the CRO industry, and more specifically with reasons for M&A, success factors during the M&A process, and why M&A can fail in the Contract Research Organization industry. The pharmaceutical industry faces increasing obstacles in respect to the development and introduction of new medications. That has to do with stricter requirements for admission and sharper controls by authorities. Today, the research and development of a new drug can easily consume more than $800 million and lasting between 10 and 15 years. Due to these facts pharmaceutical companies are looking for an alternative in the drug development process. A popular alternative is the outsourcing or in-house working with Contract Research Organizations (CRO). CRO are specialized in coordination and monitoring of drug development activities. The size of the CRO market in 2012 was around $32 billion and had an estimated market growth of around 9 – 12% for 2013. Increased outsourcing and allocation of R&D money towards CRO reflects a driving force for prospective growth. Contract Research Organizations consider mergers & acquisitions as a vital solution to achieve their objectives.
New Psychoactive Substances (NPS) is an umbrella term covering hundreds of substances across different drug groups. Many of these substances were originally developed for therapeutic use but have later appeared on the recreational drug market. The use of NPS has been associated with many outbreaks leading to hospitalizations and has been implicated in numerous fatalities worldwide. To be able to analytically detect drugs in a forensic setting is vital in the fight against the abuse of NPS. One of the most notable challenges in detection of NPS is the identification of major urinary metabolites for use as biomarkers. Furthermore, given the lack of reference standards in most metabolism studies, the major urinary metabolites can often only be tentatively determined. This thesis describes the synthesis and analysis of potential metabolites used to identify the exact structures of major metabolites of the synthetic cannabinoid AKB-48, fentanyl and five fentanyl analogues in authentic human urine samples and/or hepatocyte incubations. Synthetic targets were chosen based on previous metabolism studies by our research group. Subsequently, synthetic routes were developed to produce numerous potential metabolites across the studied NPS. The synthesized reference standards were analyzed by LC-QTOF-MS alongside hepatocyte drug incubations and authentic human urine samples. Comparison of the resulting analytical data was used to determine the exact structures of many metabolites. This includes urinary metabolites of AKB-48 with a single hydroxyl group situated on a secondary carbon of the adamantane moiety, or position 3 or 5 of the pentyl side chain. For the studied fentanyls, the ?-OH and the 4’-OH metabolites were abundant metabolites identified in hepatocyte incubations while the 4’-OH, 4’-OH-3’-OMe and 3’,4’-diOH were the favored metabolic motifs among the metabolites identified in urine. Additionally, a concise synthetic route to produce synthetic cannabinoid metabolites with the 4-OH-5F pentyl side chain motif was developed and demonstrated for four synthetic cannabinoids. These findings and the developed synthetic routes can be used to provide forensic toxicology laboratories with urinary biomarkers for drug detection. Moreover, the synthesized reference standards of major metabolites can be studied to better understand the toxicity of their parent drugs. Nya psykoaktiva substanser (NPS) är det officiella namnet för den grupp droger som tidigare har kallats för designerdroger, nätdroger eller internetdroger. NPS definieras som droger som utgör ett likvärdigt hot mot folkhälsan som droger som återfinns på Förenta Nationernas narkotikakonventioner men som själva inte återfinns under dessa konventioner. Det finns hundratals olika rapporterade NPS spridda över olika droggrupper, såsom syntetiska cannabinoider och syntetiska opioider. Vissa av dessa droger syntetiserades ursprungligen i forskningssyfte, men tog sig senare in på den illegala drogmarknaden. De mer nyligen framtagna NPS är ofta designade att efterlikna effekterna av etablerade droger, såsom morfin eller ?9-THC, vilket är den huvudsakliga psykoaktiva substansen i cannabis. Användandet av NPS har associerats till många kluster av intoxikationer som har lett till hospitaliseringar. Många har även dött till följd av användandet av NPS. Inte minst i USA där en grupp av NPS kallad för fentanylanaloger är högst delaktig i den pågående opioidkrisen. Den ständiga inströmningen av nya NPS leder till att detektion av och diskriminering mellan dem utgör en svår utmaning för forensiska toxikologilaboratorier. Tillgången av lämpliga referenssubstanser möter inte deras efterfrågan, delvis på grund av att vilka biomarkörer som är optimala för drogdetektion inte alltid är uppenbart. Till exempel så är metabolismen av syntetiska cannabinoider i regel både snabb och omfattande. Av den anledningen kan användandet av modersubstansen som biomarkör vid analys av urin leda till falskt negativa resultat. Urin som biologisk matris har många fördelar jämfört med blod. Till exempel så har urin ett längre detektionsfönster och högre drogkoncentrationer. För att kunna identifiera optimala biomarkörer för droganalys av urinprover så måste drogernas metabolism utredas. De flesta metabolismstudier använder sig av humana levermikrosomer eller hepatocyter som inkuberas tillsammans med droger för att generera metaboliter in vitro. Urinprover från individer i vilkas blod det har återfunnits droger används också men tillgången är tyvärr begränsad. Dessa metaboliter separeras sedan med hjälp av kromatografiska tekniker och deras kemiska strukturer bestäms med hjälp av masspektrometri. Dock så är utvärderingen av masspektrometridata komplicerad och det är heller inte möjligt att skilja på vissa positionsisomerer genom att enbart analysera masspektrometridata. För att kunna möjliggöra exakt strukturutredning så krävs referensstandarder. Därför var målet med denna avhandling att addera syntes och analys av referensstandarder till de etablerade tillvägagångssätten att studera metabolismen av NPS. Ett stort antal potentiella metaboliter av AKB-48 och andra syntetiska cannabinoider samt av fentanyl och fentanylanaloger syntetiserades. Genom att använda dessa referensstandarder i metabolismstudier så kunde de exakta kemiska strukturerna för många metaboliter bestämmas. Dessutom så identifierades mönster i de metaboliska profilerna bland fentanyl och fentanylanaloger. Dessa mönster kan användas för att förbättra predikteringen av metaboliter för andra nuvarande och kommande fentanylanaloger. Dessa resultat samt de utvecklade syntesvägarna kan nyttjas i framställningen av referenssubstanser i syfte att användas som biomarkörer för att i urin kunna detektera drogmissbruk. Referenssubstanserna kan även användas för att studera metaboliternas farmakologiska egenskaper vilket kan leda till en djupare förståelse kring toxiciteten hos modersubstanserna.
The first book in the crime series featuring Lars Winkler: loner, dad, former squatter, and drug addict — and the most dedicated detective in Copenhagen. A young prostitute is found murdered at the common in Copenhagen. The woman’s body has been preserved and her eyes removed with surgical precision. Not long after, another body is discovered treated in the exact same manner. The press quickly names the spectacular case the Sandman Killings. Detective Inspector Lars Winkler is put on the case. With an addiction to classical rock music and the odd line of speed, Lars is struggling to get his life back together, mostly with his sixteen-year-old daughter, Maria, who lives with him in his rundown apartment. His wife has left him for his old friend and former boss. Meanwhile, the atmosphere in the Homicide and Serious Crime Department is tense. Despite support from his new young partner, Sanne Bissen, Lars feels edged out. While tracking Copenhagen’s most sadistic serial killer to date, his past — which has long been kept secret — is slowly catching up to him.
Master's Thesis from the year 2013 in the subject Business economics - Business Management, Corporate Governance, grade: 1,0, , language: English, abstract: This thesis deals in general with mergers & acquisitions in the CRO industry, and more specifically with reasons for M&A, success factors during the M&A process, and why M&A can fail in the Contract Research Organization industry. The pharmaceutical industry faces increasing obstacles in respect to the development and introduction of new medications. That has to do with stricter requirements for admission and sharper controls by authorities. Today, the research and development of a new drug can easily consume more than $800 million and lasting between 10 and 15 years. Due to these admission, money and time pressures, pharmaceutical companies are looking for an alternative in the drug development process. A very popular alternative is the outsourcing or in-house working with Contract Research Organizations (CRO). Contract Research Organizations are specialized in coordination and monitoring of drug development activities. Due to their focus they often offer a more sophisticated and faster process. Demographic changes, chronic diseases like cancer and diabetes, and completely new cluster of symptoms demand new therapeutically treatments. The size of the CRO market in 2012 was around $32 billion and had an estimated market growth of around 9 – 12% for 2013. Increased outsourcing and allocation of R&D money towards CRO reflects a driving force for prospective growth. To benefit from the good industry outlooks CROs adjust their service offerings and strengthen their competitive situation. More and more Contract Research Organizations consider mergers & acquisitions as a vital solution to achieve their objectives. Since couple of years we can observe an increased number of deals. Large corporations can close the gaps in the internal service pipeline and smaller firms can use mergers as a financial exit. However, many M&A activities are considered as ineffective and contra-productive for the shareholder value – either destroy or merely add. Depending on the study, the numbers of M&A failures vary from 50% to even 80%. Possible reasons may be not enough integration planning and unrealistic expectations on the cost and time. The reality shows that it is not that easy to cut costs by simple combining two departments after a merger or acquisition. Additionally, we can see that mergers and acquisitions basically not succeed during the actual process.[...]
Kemal Kayankaya is the ultimate outsider among hard-boiled private eyes." --Marilyn Stasio, The New York Times Book Review OVER 1 MILLION COPIES SOLD WORLDWIDE When a Turkish laborer is stabbed to death in Frankfurt's red light district, the local polcie see no need to work overtime. But when the laborer's wife comes to him for help, wise-cracking detective Kemal Kayankaya, a Turkish immigrant himself, smells a rat. The dead man wasn't the kind of guy who spent time with prostitutes. What gives? The deeper he digs, the more Kayankaya finds that the vitim was a good guy, a poor immigrant just trying to look out for his family. So who wanted him dead, and why? On the way to find out, Kayankaya has run-ins with prostitutes and drug addicts, gets beaten up by anonymous thugs, survives a gas attack, and suffers several close encounters with a Fiat. And then there's the police cover-up he stumbles upon ...
For the vagabond pack of ex-pat Europeans, Indian Tanzanians and wealthy Africans at Moshi's International School, it's all about getting high, getting drunk and getting laid. Their parents - drug dealers, mercenaries and farmers gone to seed - are too dead inside to give a damn. Outwardly free but empty at heart, privileged but out of place, these kids are lost, trapped in a land without hope. They can try to get out, but something will always drag them back - where can you go when you believe in nothing and belong to nowhere?
The two diaries contained in this volume were written by Lieutenant Jakob Piel of the Hesse-Cassel von Lossberg Regiment and Captain Andreas Wiederhold of the Hesse-Cassel von Knyphausen Regiment. Their careers in America paralleled each other for a part
* Diagnostic criteria and differential diagnosis of COPD * GOLD severity staging and therapy * Commonly used drug formulations * Pulmonary function tests and interpretation * Concise tables of lung volumes and capacity
In this thesis, Bernhard Schmidt describes his research into two fields in the chemical sciences: supramolecular and macromolecular chemistry. Schmidt first investigates cyclodextrins (CDs), which are well known for the formation of supramolecular host/guest complexes with hydrophobic molecules in aqueous solution. Schmidt then also examines reversible addition-fragmentation chain transfer (RAFT) polymerization as a well-suited toll for the synthesis of water-soluble end-functionalized polymers. The author skillfully combines both concepts as a powerful tool to access reversibly forming macromolecular architectures. The novel methods and architectures presented in this work are highly interesting from both a fundamental point of view as well as a basis for the design of efficient drug release systems. The work in this thesis has led to a number of publications in top peer-reviewed journals.
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