bluuebunny/crossref_metadata_2025 huggingface dataset:
Organic Functional Group Protection
Authors: Taber Douglass F.
Published: November 2020

We found (Tetrahedron Lett. 2010, 51, 3545) that the superiority of KH over NaH in the Williamson ether synthesis was particularly marked with congested partners such as 1. Geert-Jan Boons of the University of Georgia described (Org. Lett. 2010, 12, 4636) the selective removal of each of the several orthogonal protecting groups decorating the disaccharide 3. Yutaka Nishiyama of Kansai University reported (Synlett 2010, 3089) a Re catalyst for the selective acylation of an ether 5, to give the ester 6, from the less substituted side. Duen-Ren Hou of National Central University showed (Tetrahedron Lett. 2010, 51, 6143) that triphenylphosphine hydrobromide was a convenient reagent for debenzylation, converting 7 into 8. Junghyun Chae of Sungshin Women’s University established (Synlett 2010, 1651) that simply microwaving an aromatic methyl ether 9 in an ionic liquid led to smooth demethylation. Allylic selenides such as 11 can serve as masked allylic alcohols. Wei-Ming Xu of Hangzhou Normal University demonstrated (Org. Lett. 2010, 12, 4431) that the polystyrene-supported Se resin facilitated the purification of 11. Oxidation followed by sigmatropic rearrangement then installed the axial secondary alcohol. Clemens Richert of the Universität Stuttgart devised (Synlett 2010, 2267) a reagent 13 for the one-step protection of an amine 14 as its azidomethyl carbamate 15. Xueshun Jia of the Shanghai Institute of Organic Chemistry showed (Tetrahedron Lett. 2010, 51, 6049) that a substoichiometric quantity of Sm metal was sufficient to mediate the acylation of the congested amine 16. Frederik Rombouts of Johnson & Johnson, Beerse, and Andrés A. Trabanco of Johnson & Johnson, Toledo, found (Tetrahedron Lett. 2010, 51, 4815) that the triflic acid debenzylation of 18 was also promoted by microwave irradiation. Mark D. Spicer and John A. Murphy of the University of Strathclyde designed (J. Am. Chem. Soc. 2010, 132, 15462) a stoichiometric Ni reagent that deprotected even the unreactive sulfonamide 20. Steven M. Weinreb of Pennsylvania State University showed (Tetrahedron Lett. 2010, 51, 3555) that an oxime can be deprotected by Fe-mediated reduction of the pivalate 22. David A. Colby of Purdue University protected (Org. Lett. 2010, 12, 5588) the ketone of 24 by forming the adduct with methoxymethylamine, allowing selective addition to the ester, to give 25.
Flow Methods for Organic Synthesis
Authors: Taber Douglass F.
Published: November 2020

Carrying out organic synthesis with a flow reactor can offer significant advantages over the more conventional batch processing. Andreas Kirschning of Leibniz Universität Hannover concisely summarized (Chem. Commun. 2011, 47, 4583) the issues surrounding both micro and meso flow methods. Walter Leitner of RWTH Aachen focused (Chem. Commun. 2011, 47, 3691) on near- and supercritical fluids as solvents, and Steven V. Ley of the University of Cambridge discussed in-line IR monitoring for the accurate dispensing of reagents in a flow apparatus (Chem. Sci. 2011, 2, 765) and cryogenic operations (Org. Lett. 2011, 13, 3312). Nicholas E. Leadbeater of the University of Connecticut addressed (Tetrahedron Lett. 2011, 52, 263) the handling of solid reaction products, and Thomas Wirth of Cardiff University (Angew. Chem. Int. Ed. 2011, 50, 357) and Martyn Poiakoff of the University of Nottingham (Angew. Chem. Int. Ed. 2011, 50, 3788) outlined software-based reaction optimization. A recent monograph (reviewed in J. Am. Chem. Soc. 2011, 133, 9948) by Charlotte Wiles of Chemtrix BV and Paul Watts of the University of Hull provides a detailed overview of many of these issues. Simple thermal reactions are easily carried out under flow conditions, with optimized temperature and dwell times. Peter H. Seeberger of Max Planck Potsdam carried out (Chem. Commun. 2011, 47, 2688) the Hemetsberger-Knittel cyclization of 1 to the indole 2, and Lukas J. Goossen of TU Kaiserslautern and Toby Underwood of Pfizer/Sandwich effected ( Chem. Commun. 2011, 47, 3628) the decarboxylative coupling of 3 with 4 to give 5. A flow apparatus can also be used for gas-liquid reactions. C. Oliver Kappe of Karl-Franzen University Graz effected (Org. Lett. 2011, 13, 984) ozonolysis of 6, using the Dussault protocol, and Dong-Pyo Kim of Chungnam National University generated (Angew. Chem. Int. Ed. 2011, 50, 5952) diazomethane in situ to homologate 8 to 9. Mixing can be a serious issue under flow conditions. Sarah J. Dolman of Merck Process observed (J. Org. Chem. 2011, 76, 993) that kinetic deprotonation and formylation of 10 gave 11, but that formylation after aging led to increasing quantities of 12. Using magnetically driven agitation in a tube mixer, she was able to make 11 the dominant product from the flow procedure.
Stereoselective C-O Ring Construction: The Jamison Synthesis of (-)-Gloeosporone
Authors: Taber Douglass F.
Published: November 2020

Arene diazonium salts are effective precursors for the Heck reaction. Sandro Cacchi of the Università degli Studi “La Sapienza,” Roma, observed (Synlett 2009, 1277) that the diazonium salt generated in situ from 1 coupled with 2 to deliver the butenolide 3. Daniel J. Canney of Temple University established (Tetrahedron Lett. 2009, 50, 5914) conditions for the homologation of an alkenyl ester such as 4 to the homologated lactone 5. Tsutomu Katsuki of Kyushu University established (J. Am. Chem. Soc. 2009, 131, 14218) that Ir-mediated C-H insertion converted 6 into 8 with high diastereo- and enantiocontrol. Thomas J. J. Müller of the Heinrich-Heine-Universität, Düsseldorf, optimized ( Adv. Synth. Cat. 2009, 351, 2921) the Rh-mediated enantioselective cycloisomerization of 9 to 10. Santosh J. Gharpure of the Indian Institute of Technology, Madras, showed (Organic Lett. 2009, 11, 5466) that the intramolecular cyclopropanation of 11 proceeded with high diasterocontrol. Reduction of the intermediate cyclopropane then delivered the cyclic ether 12. Brian L. Pagenkopf of the University of Western Ontario optimized (Organic Lett. 2009, 11, 5614) the diastereoselective Co-catalyzed oxidative cyclization of 13 to 14. Mark C. Bagley and Andrew E. Graham of Cardiff University found (Tetrahedron Lett. 2009, 50, 6823) that microwave heating promoted the selective BaMnO4 oxidation of 1,3-, 1,4-, and 1,5-diols such as 15 to the corresponding lactones. David W. Lupton of Monash University developed (J. Am. Chem. Soc. 2009, 131, 14176) the remarkable cyclization of 17 to 19, catalyzed by the carbene precursor 18. Hirokazu Urabe of the Tokyo Institute of Technology showed (J. Am. Chem. Soc. 2009, 131, 3166) that the unusual Rh-catalyzed cyclization of an alkynyl sulfone 20 proceeded with substantial diastereocontrol, delivering the cyclic ether 21 as the major product. Jeffrey S. Johnson of the University of North Carolina established (J. Am. Chem. Soc. 2009, 131, 14202) that Sc(OTf)3 was a particularly efficient catalyst for the opening of 22 with 23 and then reclosure, leading to 24. Steven D. R. Christie and Gareth J. Pritchard of Loughborough University (Chem. Commun. 2009, 7339) and Michael A. Kerr of the University of Western Ontario (J. Org. Chem. 2009, 74, 8414) investigated related condensations.
Synthesis of Naturally Occurring Cyclic Ethers: Boivivianin B (Murakami), SC- Δ 13 -9-IsoF (Taber), Brevisamide (Panek, Lindsley,Ghosh), Gambierol (Mori)
Authors: Taber Douglass F.
Published: November 2020

The challenge of controlling the relative and absolute configuration of highly substituted cyclic ether-containing natural products continues to stimulate the development of new synthetic methods. Masahiro Murakami of Kyoto University showed (J. Org. Chem. 2009, 74, 6050) that Rh-mediated addition of an aryl boronic acid to 1 proceeded with high syn diastereocontrol, giving 3. This set the stage for Au-mediated rearrangement, leading to 4. We found (J. Org. Chem. 2009, 74, 5516) that asymmetric epoxidation of 5 followed by exposure to AD-mix could be used to prepare each of the four diastereomers of 6. We carried 6 on the isofuran 7, using a stereodivergent strategy that allowed the preparation of each of the 32 enantiomerically pure diastereomers of the natural product. Following up on the synthesis of brevisamide 16 described (Organic Highlights, November 16, 2009) by Kazuo Tachibana of the University of Tokyo, three groups reported alternative total syntheses. James S. Panek of Boston University prepared (Organic Lett. 2009, 11, 4390) the cyclic ether of 16 by addition of the enantiomerically pure silane 9 to 8. Craig W. Lindsley of Vanderbilt University used (Organic Lett. 2009, 11, 3950) SmI2 to effect the cyclization of 11 to 12. Arun K. Ghosh of Purdue University employed (Organic Lett. 2009, 11, 4164) an enantiomerically pure Cr catalyst to direct the absolute configuration in the hetero Diels-Alder addition of 14 to 13. Rubottom oxidation of the enol ether so formed led to the α-hydroxy ketone 15. Yuji Mori of Meijo University described (Organic Lett. 2009, 11, 4382) the total synthesis of the Gambierdiscus toxicus ladder ether gambierol 19. A key strategy, used repeatedly through the sequence, was the exo cyclization of an epoxy sulfone, illustrated by the conversion of 17 to 18. The epoxy sulfones were prepared by alkylating the anions derived from preformed epoxy sulfones such as 20.
Stereoselective C-O Ring Construction: (+)-Pachastrissamine (Fujii/Ohno), Aspalathin (Minehan), (+)-Varitriol (Ghosh), Aspercyclide A (Spivey), Etnangien (Menche)
Authors: Taber Douglass F.
Published: November 2020

(+)-Pachastrissamine 3, also known as jaspine B, induces apoptosis in melanoma cells by a caspase-dependent pathway. Nobutaka Fujii and Hiroaki Ohno of Kyoyo University developed (J. Org. Chem. 2010, 75, 3831) a practical route to 3 based on the Pd-mediated cyclization of 1 to 2. Thomas G. Minehan of California State University, Northridge, optimized (Organic Lett. 2010, 12, 1580) the condensation of 5 with the bis-pivalate 4. This opened a general route to C-aryl glycosides, including aspalathin 6. (+)-Varitriol 11 is vinylogously related to 7. A key step in the synthesis of 11 reported (J. Org. Chem. 2010, 75, 2107) by Subhash Ghosh of the Indian Institute of Chemical Technology was the intermolecular Heck coupling of 8 with 9. Aspercyclide A 14 and its more stable methyl ether are promising lead compounds for the treatment of asthma. In the course of a synthesis of 14, Alan C. Spivey of Imperial College developed (Chem. Commun. 2010, 1824) the intramolecular Heck cyclization of 12 to 13. In a bold synthesis of etnangien 17, Dirk Menche of Ruprecht-Karls-Universität Heidelberg showed (J. Org. Chem. 2010, 75, 2429) that the intramolecular Heck coupling of 15 to 16 proceeded efficiently. The substituents on 15 may be favoring conformations that lead to cyclization.
Heteroaromatic Construction: The Jia Synthesis of (-)- cis -Clavicipitic Acid
Authors: Taber Douglass F.
Published: November 2020

Simultaneously, Aaran Aponick of the University of Florida (Organic Lett. 2009, 11, 4624) and Shuji Akai of the University of Shizuoka (Organic Lett. 2009, 11, 5002) reported the Au-mediate conversion of a propargylic diol such as 1 to the furan 2. Pyrroles can also be prepared using the same protocol. Jason K. Sello of Brown University developed (Organic Lett. 2009, 11, 2984) the direct aldol condensation of an acetoacetate 3 with the protected 1,3-dihydroxy acetone 4 to give 5, the methyl ester of a methylenomycin furan (MMF) bacterial-signaling molecule from Streptomyces coelicolor. Nobuharu Iwasawa of the Tokyo Institute of Technology demonstrated (Angew. Chem. Int. Ed. 2009, 48, 8318) that the imine 6 was sufficiently nucleophilic to react with the Rh vinylidene derived from the alkyne 7, leading to the pyrrole 8. Min Shi of the Shanghai Institute of Organic Chemistry extended (J. Org. Chem. 2009, 74, 5983) the reactivity of methylene cyclopropanes to the condensation of the aldehyde 9 with an acyl hydrazide, to give the pyrrole 11. Xue-Long Hou, also of the Shanghai Institute of Organic Chemistry, described (Tetrahedron Lett. 2009, 50, 6944) the Au-mediated reorganization of the alkynyl aziridine 12 to the pyrrole 13. Masahiro Yoshida of the University of Tokushima carried out (Tetrahedron Lett. 2009, 50, 6268) a similar rearrangement under oxidative conditions, giving the iodinated pyrrole 15. André M. Beauchemin of the University of Ottawa showed (Angew. Chem. Int. Ed. 2009, 48, 8325) that under acid catalysis, the oxime 16 cyclized to the pyridine 17. Shunsuke Chiba of Nanyang Technological University developed (J. Am. Chem. Soc. 2009, 131, 12570) the Mn(III)-mediated fusion of a cyclopropanol 18 with an alkenyl azide 19 to deliver the pyridine 20. Kazuaki Shimada of Iwate University found (Tetrahedron Lett. 2009, 50, 6651) that an isotellurazole such as 21, easily prepared from the corresponding alkyne, condensed with another alkyne 22, delivering the pyridine 23 with high regiocontrol. Christopher J. Moody of the University of Nottingham devised (Organic Lett. 2009, 11, 3686) a new route to the 1,2,4-triazine 24 from an α-diazoacetoacetate. He carried 24 on to the pyridine 26 by condensation with norbornadiene 25.
The Corey Synthesis of (+)-Lupeol
Authors: Taber Douglass F.
Published: November 2020

The total synthesis of lupeol was one of the crowning achievements of the Robinson annulation/ reductive alkylation approach to stereocontrolled polycarbocyclic construction developed by Gilbert Stork (J. Am. Chem. Soc. 1971, 93, 4945). It is a measure of the progress of organic synthesis since that time that E. J. Corey of Harvard University could devise (J. Am. Chem. Soc. 2009, 131, 13928) an enantioselective synthesis of (+)-lupeol 3 that could be carried out by a single colleague. The key step in the synthesis was the Lewis acid–mediated cyclization of 1 to 2. The preparation of 1 began with the enantioselective epoxidation of farnesol acetate 4. To this end, asymmetric dihydroxylation delivered the diol 5. Selective mesylation followed by exposure to dilute methoxide effected ring closure to the epoxide, but also removed the acetate, so this had to be reapplied. The synthesis of the aromatic portion of 1 started with the phenol 7. Protection as the very bulky triisopropylsilyl ether was important for the success of the subsequent cyclization, perhaps because it discouraged complexation of the Lewis acid with the aryl ether. Metalation followed by formylation delivered the aldehyde 8, which was reduced and carried on to the bromide 9. The derived Grignard reagent coupled smoothly with 6 under Li2CuCl4 catalysis. The cyclization of 1 to 2 proceeded with remarkable efficiency (43%!), for a reaction in which three new C-C bonds, four rings, and five new stereogenic centers were established. It is particularly noteworthy that the cyclization cleanly set the trans, anti, trans, anti tetra-cyclic backbone of (+)-lupeol 3. To complete the synthesis of 3, the less substituted alkene of 2 was selectively hydrogenated, then CH3 Li was added to give 10. Hydrolysis and dehydration yielded 11, which was reduced and equilibrated to 12. On brief exposure to MsCl/Et3 N, 13 cyclized to (+)-lupeol 3. It is a measure of the remarkable effi ciency of this synthesis of (+)-lupeol 3 that it provided suffi cient material to enable studies of the rearrangement of 3 under acidic conditions to other pentacyclic triterpenes, including, inter alia, germanicol, α -amyrin, δ -amyrin, and taraxasterol 14 .
The Bradshaw/Bonjoch Synthesis of (-)-Anominine
Authors: Taber Douglass F.
Published: November 2020

The Hajos-Parrish cyclization was a landmark in the asymmetric construction of polycarbocyclic natural products. Impressive at the time, the proline-mediated intramolecular aldol condensation proceeded with an ee that was low by modern standards. Ben Bradshaw and Josep Bonjoch of the Universitat de Barcelona optimized this protocol, then used it to prepare (J. Am. Chem. Soc. 2010, 132, 5966) the enone 3 en route to the Aspergillus alkaloid (-)-anominine 4. The optimized catalyst for the enantioselective Robinson annulation was the amide 5 . With 2.5 mol % of the catalyst, the reaction proceeded in 97% ee. With only 1 mol % of catalyst, the reaction could be taken to 96% yield while maintaining the ee at 94%. Conjugate addition proceeded across the open face of 3 to give, after selective protection, the monoketal 7. After methylenation and deprotection, oxidation with IBX delivered the enone 9. With the angular quaternary centers of the natural product in place, the molecule became increasingly congested. Attempted direct alkylation of 9 led mainly to O-methylation. A solution to this problem was found in condensation with the Eschenmoser salt, followed by N-oxide formation and elimination to give the tetraene 10. Selective reduction by the Ganem protocol followed by equilibration completed the net methylation. Under anhydrous conditions, the oxide derived from the allylic selenide 12 did not rearrange. On the addition of water, the rearrangement proceeded smoothly. Protection and hydroboration converted 13 into 14. The bulk of the folded molecule protected the exo methylene of 14, so hydrogenation followed by protection and oxidation delivered 15. Conjugate addition of indole to 15 set the stage for oxidation and bis-methylenation to give 17. Selective Ru-mediated cross-coupling with 18 followed by deprotection then completed the synthesis of (-)-anominine 4, which proved to be the enantiomer of the natural product.
Background
Authors: Ahlskog J. Eric
Published: November 2020

This book has a combined focus on two neurodegenerative conditions: dementia with Lewy bodies and Parkinson’s disease with dementia. While patients with either disorder experience quite variable problems, these two disorders have striking similarities when viewed in the aggregate. Thus, the symptoms of these two conditions are much the same, and so are the treatment strategies. Before addressing treatment, it is crucial to define the relevant terms, broaden our understanding, and discuss how these diagnoses are made. We will start with some basics. These disorders typically start in middle age and later, where selected brain circuits deteriorate for unknown reasons. Common neurodegenerative conditions include Parkinson’s disease, Alzheimer’s disease, and amyotrophic lateral sclerosis (ALS; Lou Gehrig’s disease). Such conditions involve limited regions of the brain or spinal cord, slowly progressing and leading to disability. Each is clinically identified by the specific neurologic deficits unique to that condition. Why each affects certain brain regions, sparing others, is a crucial but unanswered question. Although much has been learned about degenerative syndromes, we do not know the causes of any of them. Dementia implies a loss of intellectual abilities sufficient to compromise activities of daily living. Most often the term dementia is used in the context of neurodegenerative disorders. Mild thinking and memory problems that do not substantially interfere with daily routines fall into the category of mild cognitive impairment (MCI; see below). Doctors diagnosing dementia rely on the history from the patient and family, plus cognitive tests. Short tests assessing memory, attention, and calculation, among other things, can be done in the doctor’s office. Such tests include the so-called Mini-Mental State Examination and the Short Test of Mental Status. More refined and informative tests, termed psychometric testing, are done under the auspices of psychologists; these typically require 2 to 4 hours. Clinicians addressing dementia must also look for treatable causes before concluding that the problem is a neurodegenerative dementia. This assessment typically includes a brain scan, blood tests, and a review of the patient’s medical history and medication list, which may indicate the need for additional testing.
Unstable Responses and Dyskinesias: Later Motor Problems
Authors: Ahlskog J. Eric
Published: November 2020

Chapter 6 outlined the symptoms that should benefit from carbidopa/levodopa treatment and how to initiate it. Once the optimum dosing scheme has been established there usually is not much medication adjustment required for the initial few years. However, this situation changes with longer durations of DLB or Parkinson’s disease. During the first several years of DLB or Parkinson’s disease, treatment with carbidopa/levodopa is straightforward—the responses are stable and unchanging over the course of the day. Thus, the exact time a person takes the doses is not important as long as they are administered on an empty stomach (at least 1 hour before and 2 hours after meals). If the dosage is changed, it takes about a week for the response to fully develop. This pattern of a stable levodopa response that slowly accumulates over a week is termed the long-duration response. For this response to fully develop and capture the maximum benefit, about six to eight tablets of the regular (immediate-release) carbidopa/levodopa 25/100 tablets per day are necessary. While this has not been well studied in clinical trials, experience in the clinic suggests that this is approximately correct. After a few years of having DLB or Parkinson’s disease, the person’s response to levodopa tends to change. The long-duration effect persists, but part of the benefit becomes time-locked to each dose. This response does not reflect how long the person has been taking carbidopa/levodopa but how long he or she has had DLB or Parkinson’s disease. As these conditions progress, the capacity to maintain a stable, around-the-clock effect from levodopa diminishes, as if the effect could no longer be stored-up. This is not simply a brain levodopa storage problem, but it behaves that way. People with this time-locked benefit from levodopa will note that their gait, stiffness, tremor, and slowness will improve an hour or so after taking a carbidopa/levodopa dose. In other words, it takes about an hour (sometimes less) for the regular carbidopa/levodopa to “kick in.” Initially, this benefit may last 4 to 5 hours, but after many years it may diminish to 2 hours or less.
Cultivating Stories of Strength and Meaning and Deconstructing Damaging Discourses: The Course of Treatment
Authors: Hamkins SuEllen
Published: November 2020

Listening for narratives of strength and meaning that have not yet been told but are implicit in the patient’s experience is key to the art of narrative psychiatry. In any conversation, there are many openings for finding exceptions to the activities and effects of problems. Each exception to the problem is a seed that can be cultivated into a narrative by fleshing it out with detail, linking it to other exceptions over time, and articulating the meanings that these exceptions have for the person. This new narrative offers fertile ground for freshly imagining what might be possible in the future. It sustains valued aspects of identity and points the way toward freedom from the problem. At the same time that we are nurturing nascent stories of skill and resilience, we are also listening for narratives that fuel problems, so that they may be examined, dismantled, and replaced with narratives that support well-being. Stories that fuel problems come from many sources. For example, someone who is dealing with depression may be influenced by a family story of being the “problem child,” a local story that derides those who seek mental health treatment, and a wider cultural story that narrowly defines a successful life in terms of money. These narratives can be named and closely examined in light of the patient’s own values, allowing the patient more choice over which narratives are taken up and which are set aside. Narrative psychiatry continuously attends to the patient’s social context. Often, the people who consult with us are living under the influence of cultural discourses that make negative claims about their worthiness, seek to limit their prospects, and engage them in processes of self-scrutiny that lead to anxiety or despair. By discourses I mean narratives and practices that share a common value. These discourses include those that privilege or denigrate people on the basis of their race, gender, gender preference, sexual preference, body type, financial status, education, health, or ability. Narrative psychiatry attends to issues of power—of privilege and oppression—and deconstructs the operations of power as they influence someone’s life.
The Theoretical Basis for Assignment by NMR
Authors: Seco Josi M. , Quiqoa Emilio , Riguera Ricardo
Published: November 2020

The nuclear magnetic resonance (NMR) spectra of two enantiomers are identical. Thus, the first step in using NMR to distinguish between two enantiomers should be to produce different spectra that eventually can be associated with their different stereochemistry (i.e., the assignment of their absolute configuration). Therefore, it is necessary to introduce a chiral reagent in the NMR media. There are two ways to address this problem. One is to use a chiral solvent, or a chiral agent, that combines with each enantiomer of the substrate to produce diastereomeric complexes/associations that lead to different spectra. This is the so-called chiral solvating agent (CSA) approach; it will not be further discussed here [33–34]. The second approach is to use a chiral auxiliary reagent [13–15] (i.e., a chiral derivatizing agent; CDA) that bonds to the substrate by a covalent linkage. Thus, in the most general method, the two enantiomers of the auxiliary CDA react separately with the substrate, giving two diastereomeric derivatives whose spectral differences carry information that can be associated with their stereochemistry. The CDA method that employs arylalcoxyacetic acids as auxiliaries is the most frequently used. It can be applied to a number of monofunctionals [14–15] (secondary alcohols [35–43], primary alcohols [44–46], aldehyde [47] and ketone cyanohydrins [48–49], thiols [50–51], primary amines [52–56], and carboxylic acids [57–58]), difunctional [13] (sec/sec-1,2-diols [59–61], sec/sec-1,2-amino alcohols [62], prim/sec-1,2-diols [63–65], prim/sec-1,2-aminoalcohols, and sec/prim-1,2-aminoalcohols [66–68]), and trifunctional (prim/sec/sec-1,2,3-triols [13, 69–70]) chiral compounds. Its scope and limitations are well established, and its theoretical foundations are well known, making it a reliable tool for configurational assignment. Figure 1.1 shows a summary of the steps to be followed for the assignment of absolute configuration of a chiral compound with just one asymmetric carbon and with substituents that, for simplicity, are assumed to resonate as singlets. Step 1 (Figure 1.1a): A substrate of unknown configuration (?) is separately derivatized with the two enantiomers of a chiral auxiliary reagent, (R)-Aux and (S)-Aux, producing two diastereomeric derivatives.
Exercises
Authors: Seco Josi M. , Quiqoa Emilio , Riguera Ricardo
Published: November 2020

This chapter contains fifty exercises in the use of the methods described in the previous pages to the assignment of the absolute configuration of different substrates. They are organized according to the functional group of the substrate and follow the same order as in the previous chapters: alcohols; cyanohydrins; thiols; amines; carboxylic acids; 1,n-diols; 1,2-amino alcohols; and 1,2,3-triols. For each class of functional groups, there are exercises related to all the procedures available for assignment, such as double and single derivatization, and with different CDAs, when this is relevant. The derivatives and their spectra are actual data obtained in our laboratory; they are not simulated. Therefore, in a few cases, the spectra is not of high quality due to a small sample size or impurities that affect the result. In the spectra provided in the exercises below, in most cases, we have labeled the signals relevant for assignment; however, when the structure of the substrate and the spectra are simple, no signal identification is provided. At the end of this chapter, we provide a list of references to the literature in which the solutions can be found.
Image Force on a Screw Dislocation Inside an Elastic or a Piezoelectric Inhomogeneity of Arbitrary Shape
Authors: Wang Xu , Yang Ping , Schiavone Peter
Published: November 2020

A novel and effective method is proposed to determine the image force acting on a screw dislocation located inside an elastic inhomogeneity of arbitrary shape perfectly bonded to an infinite elastic matrix. The basis for our representation of the image force stems from the fact that the analytic function defined inside the elastic inhomogeneity can be conveniently constructed from the continuity conditions of traction and displacement across the perfect interface. An identical method is employed to derive the image force on a screw dislocation inside a piezoelectric inhomogeneity of arbitrary shape.
De novo lupus nephritis during treatment with belimumab
Authors: Parodis Ioannis , Vital Edward M , Hassan Sabih-Ul , Jönsen Andreas , Bengtsson Anders A , Eriksson Per , Leonard Dag , Gunnarsson Iva , Rönnblom Lars , Sjöwall Christopher
Published: November 2020

Objective

In light of reports of de novo LN during belimumab (BLM) treatment, we sought to determine its frequency and contributing or protective factors in a real-life setting.

Methods

Patients with SLE who received BLM between 2011 and 2017 at five European academic practices were enrolled (n = 95) and followed longitudinally for a median time of 13.1 months [interquartile range (IQR): 6.0–34.7]; 52.6% were anti-dsDNA positive, 60.0% had low complement levels, and 69.5% had no renal involvement prior to/at BLM initiation [mean disease duration at baseline: 11.4 (9.3) years]. Age- and sex-matched patients with non-renal SLE who had similar serological profiles, but were not exposed to BLM, served as controls (median follow-up: 132.0 months; IQR: 98.3–151.2).

Results

We observed 6/66 cases (9.1%) of biopsy-proven de novo LN (4/6 proliferative) among the non-renal BLM-treated SLE cases after a follow-up of 7.4 months (IQR: 2.7–22.2). Among controls, 2/66 cases (3.0%) of de novo LN (both proliferative) were observed after 21 and 50 months. BLM treatment was associated with an increased frequency and/or shorter time to de novo LN [hazard ratio (HR): 10.7; 95% CI: 1.7, 67.9; P = 0.012], while concomitant use of antimalarial agents along with BLM showed an opposing association (HR: 0.2; 95% CI: 0.03, 0.97; P = 0.046).

Conclusion

Addition of BLM to standard-of-care did not prevent LN in patients with active non-renal SLE, but a favourable effect of concomitant use of antimalarials was implicated. Studies of whether effects of B-cell activating factor inhibition on lymphocyte subsets contribute to LN susceptibility are warranted.
Polymyositis: is there anything left? A retrospective diagnostic review from a tertiary myositis centre
Authors: Loarce-Martos Jesus , Lilleker James B , Parker Matthew , McHugh Neil , Chinoy Hector
Published: November 2020

Objective

The current classification criteria for idiopathic inflammatory myopathy (IIM) retain PM as a major disease subgroup. However, evolution in the understanding of IIM has suggested that many of these patients could be better described as having an alternative diagnosis. In the present study, we apply the latest understanding of IIM subtyping to retrospectively review PM diagnoses in a large cohort of IIM patients.

Methods

Within a previously reported cohort of 255 patients from a UK tertiary myositis clinic, 37 patients classified as PM according to both the EULAR/ACR IIM criteria and expert opinion were identified. Clinical data and complementary tests were reviewed, and consensus decisions regarding final classification were reached in each case.

Results

Nine (9/37, 24.3%) patients remained classified as PM, 3.5% (9/255) of the original cohort; these PM patients were seronegative for myositis antibodies, responsive to immunosuppression, and in 4/7 (57.1%) patients where muscle biopsy was performed had HLA-1 upregulation and endomysial inflammatory infiltrates. Immune-mediated necrotizing myopathy (5/37, 13.5%) and connective tissue disease overlap myositis (7/37, 19%) were the main alternative diagnoses. The remaining patients were diagnosed as: unspecified myopathy (6/37, 16%), dermatomyositis (2/37, 5%), cancer-associated myopathy (3/37, 8.1%), and non-inflammatory myopathy (1/37, 3%, myofibrillar myopathy). Four patients (4/37, 10%) had insufficient data available to confidently reclassify.

Conclusion

Our study confirms that PM can now be considered a rare IIM subgroup. A thorough examination, complete myositis autoantibody panel, and careful interpretation of the biopsy results is recommended to confirm the correct IIM sub-type.
Overcoming Rest–Task Divide—Abnormal Temporospatial Dynamics and Its Cognition in Schizophrenia
Authors: Northoff Georg , Gomez-Pilar Javier
Published: November 2020

Schizophrenia is a complex psychiatric disorder exhibiting alterations in spontaneous and task-related cerebral activity whose relation (termed “state dependence”) remains unclear. For unraveling their relationship, we review recent electroencephalographic (and a few functional magnetic resonance imaging) studies in schizophrenia that assess and compare both rest/prestimulus and task states, ie, rest/prestimulus–task modulation. Results report reduced neural differentiation of task-related activity from rest/prestimulus activity across different regions, neural measures, cognitive domains, and imaging modalities. Together, the findings show reduced rest/prestimulus–task modulation, which is mediated by abnormal temporospatial dynamics of the spontaneous activity. Abnormal temporospatial dynamics, in turn, may lead to abnormal prediction, ie, predictive coding, which mediates cognitive changes and psychopathological symptoms, including confusion of internally and externally oriented cognition. In conclusion, reduced rest/prestimulus–task modulation in schizophrenia provides novel insight into the neuronal mechanisms that connect task-related changes to cognitive abnormalities and psychopathological symptoms.
Consumer Behavior
Authors: Einstein Mara
Published: November 2020

What is consumer behavior?

Consumer behavior is defined as “the mental and emotional processes and the physical activities of people who purchase and use goods and services to satisfy particular needs and wants.”1 Let’s break this down a bit. “Mental and emotional...
Creative
Authors: Einstein Mara
Published: November 2020

What constitutes good advertising?

The best advertising combines creativity that engages consumers and stimulates them to buy while incorporating the strategic objectives of the marketer. Balancing these two goals is at the heart of numerous battles between advertisers and their agencies: the work may...
Radicalization to Terrorism
Authors: Moskalenko Sophia , McCauley Clark
Published: November 2020

Terrorism and radicalization came to the forefront of news and politics in the US after the unforgettable attacks of September 11th, 2001. When George W. Bush famously asked "Why do they hate us?," the President echoed the confusion, anger and fear felt by millions of Americans, while also creating a politicized discourse that has come to characterize and obscure discussions of both phenomenon in the media. Since then the American public has lived through a number of domestic attacks and threats, and watched international terrorist attacks from afar on television sets and computer screens. The anxiety and misinformation surrounding terrorism and radicalization are perhaps best detected in questions that have continued to recur in the last decade: "Are terrorists crazy?"; "Is there a profile of individuals likely to become terrorists?"; "Is it possible to prevent radicalization to terrorism?" Fortunately, in the two decades since 9/11, a significant body of research has emerged that can help provide definitive answers. As experts in the psychology of radicalization, Sophia Moskalenko and Clark McCauley propose twelve mechanisms that can move individuals, groups, and mass publics from political indifference to sympathy and support for terrorist violence. Radicalization to Terrorism: What Everyone Needs to Know synthesizes original and existing research to answer the questions raised after each new attack, including those committed by radicalized Americans. It offers a rigorously informed overview of the insight that will enable readers to see beyond the relentless new cycle to understand where terrorism comes from and how best to respond to it.
Sudan, South Sudan, and Darfur
Authors: Natsios Andrew S.
Published: November 2020

For thirty years Sudan has been a country in crisis, wracked by near-constant warfare between the north and the south. But on July 9, 2011, South Sudan became an independent nation. As Sudan once again finds itself the focus of international attention, former special envoy to Sudan and director of USAID Andrew Natsios provides a timely introduction to the country at this pivotal moment in its history. Focusing on the events of the last 25 years, Natsios sheds light on the origins of the conflict between northern and southern Sudan and the complicated politics of this volatile nation. He gives readers a first-hand view of Sudan's past as well as an honest appraisal of its future. In the wake of South Sudan's independence, Natsios explores the tensions that remain on both sides. Issues of citizenship, security, oil management, and wealth-sharing all remain unresolved. Human rights issues, particularly surrounding the ongoing violence in Darfur, likewise still clamor for solutions. Informative and accessible, this book introduces readers to the most central issues facing Sudan as it stands on the brink of historic change.
Fossil Fuels
Authors: Goldemberg José
Published: November 2020

What are the fossil fuels?

Fossil fuels—coal, petroleum, natural gas, and their by-products— account for approximately 85% of the world′s primary energy needs today. Use of these fuels drives industrialized economies and has become an integral part of every aspect of productive activity and...
Exhaustion of Fossil Fuels and Energy Security
Authors: Goldemberg José
Published: November 2020

Are fossil fuels being exhausted?

Although fossil fuel reserves are very large, they are, by nature, exhaustible. As we have discussed previously, the expected life of presently identified reserves is 41 years for oil, 63 years for natural gas, and 147 years for coal....
Burma/Myanmar
Authors: Steinberg David
Published: November 2020

It is unlikely that any country in Asia in recent years has undergone such internal policy shifts in so short a time as Myanmar. Until recently, the former British colony had one of the most secretive, corrupt, and repressive regimes on the planet, a country where Nobel Peace Prize laureate Aung San Suu Kyi was held in continual house arrest and human rights were denied to nearly all. Yet events in Myanmar since the elections of November 2010 have profoundly altered the internal mood of the society, and have surprised even Burmese and seasoned foreign observers of the Myanmar scene. The pessimism that pervaded the society prior to the elections, and the results of that voting that prompted many foreign observers to call them a “sham” or “fraud,” gradually gave way to the realization that for reasons, variously interpreted, positive change was in the air. Taking into account the dramatic changes the country has seen in the past two years-including the establishment of a human rights commission, the release of political prisoners, and reforms in health and education-David I. Steinberg offers an updated second edition of Burma/Myanmar: What Everyone Needs to Know. More than ever, the history, culture, and internal politics of this country are crucial to understanding the breaking headlines emerging from it today and placing them in a broader context. Geographically strategic, Burma/Myanmar lies between the growing powers of China and India, and has a thousand-year history as an important realm in the region-yet it is mostly unknown to Westerners. Burma/Myanmar is a place of contradictions: a picturesque land with mountain jungles and monsoon plains, it is one of the world's largest producers of heroin. Though it has extensive natural resources including oil, gas, teak, metals, and minerals, it is one of the poorest countries in the world. And despite a half-century of military-dominated rule, change is beginning to work its way through the beleaguered nation, as it moves to a more pluralistic administrative system reflecting its pluralistic cultural, multi-ethnic base. Authoritative and balanced, Burma/Myanmar is an essential book on a country in the throes of historic change.
Marine Pollution
Authors: Weis Judith S.
Published: November 2020

Marine pollution occurs today in varied forms—chemical, industrial, and agricultural-and the sources of pollution are endless. In recent history, we've seen oil spills, untreated sewage, eutrophication, invasive species, heavy metals, acidification, radioactive substances, marine litter, and overfishing, among other significant problems. Though marine pollution has long been a topic of concern, it has very recently exploded in environmental, economic, and political debate circles; scientists and non-scientists alike continue to be shocked and dismayed at the sheer diversity of water pollutants and the many ways they can come to harm our environment and our bodies. In Marine Pollution: What Everyone Needs to Know, Judith Weis covers marine pollution from many different angles, each fascinating in its own right. Beginning with its sources and history, the book describes in detail each common pollutant, why exactly it is harmful, why it may draw controversy, and how we can prevent it from destroying our aquatic ecosystems. Weis discusses topics like what actually happened with the Exxon Valdez, and why Harmful Algal Blooms are a serious concern. Later chapters will discuss pollutants that are only now surfacing as major threats, such as pharmaceuticals, personal care products, and metal nanoparticles, and explain how these can begin in the water and progress up the food chain and emerge in human bodies. The book's final section will discuss the effects of climate change and acidification on marine pollution levels, and how we can reduce pollution at the local and global levels.
Impact of a 50-Year Premedical Postbaccalaureate Program in Graduating Physicians for Practice in Primary Care and Underserved Areas
Authors: Smitherman Herbert C. , Aranha Anil N.F. , Matthews De’Andrea , Dignan Andrew , Morrison Mitchell , Ayers Eric , Robinson Leah , Smitherman Lynn C. , Sprague Kevin J. , Baker Richard S.
Published: November 2020

Purpose

To evaluate the effectiveness of Wayne State University School of Medicine’s (WSUSOM’s) 50-year premedical postbaccalaureate program (PBP)—the first and oldest in the United States—in achieving its goals, as measured by medical school matriculation and graduation, primary care specialization, and current practice location.

Method

A retrospective study of a complete comparative dataset of 9,856 WSUSOM MD graduates (1979–2017) was performed in July–August 2018. This included 539 graduates who were admitted to the PBP between 1969 and 2012. Data collected included PBP students’ sociodemographics, postgraduate specialization, residence location at time of admission to the PBP, and current medicine practice location. Health professional shortage areas (HPSAs) and medically underserved areas/populations (MUA/Ps) were determined for residence at admission to the PBP and current medicine practice location.

Results

Of the 539 PBP students, 463/539 (85.9%) successfully completed the PBP and matriculated to WSUSOM. Of those, 401/463 (86.6%) obtained an MD, and of those, 233/401 (58.1%) were female and 277/401 (69.1%) were African American. Average investment per PBP student was approximately $52,000 and for an MD graduate was approximately $77,000. The majority of PBP MD graduates with current practice information resided in HPSAs or MUA/Ps at admission to PBP (204/283, 72.1%) and were currently practicing in HPSAs or MUA/Ps (232/283, 82.0%), and 139/283 (49.1%) became primary care physicians (PCPs). Comparison of WSUSOM PBP and non-PBP MD graduates showed PBP physicians become PCPs and practice in HPSAs or MUA/Ps at higher rates than non-PBP physicians (P < .001).

Conclusions

The PBP was successful in graduating a large proportion of physicians from socioeconomically disadvantaged and diverse backgrounds, who practice as PCPs and who practice in HPSAs and MUA/Ps, thereby accomplishing the PBP’s goals of helping to address the broad health care needs of all people in the United States.
A Novel Epidemiological Approach to Geographically Mapping Population Dry Eye Disease in the United States Through Google Trends
Authors: Azzam Daniel B. , Nag Nitish , Tran Julia , Chen Lauren , Visnagra Kaajal , Marshall Kailey , Wade Matthew
Published: November 2020

Purpose:

Our study fills the spatiotemporal gaps in dry eye disease (DED) epidemiology by using Google Trends as a novel epidemiological tool for geographically mapping DED in relation to environmental risk factors.

Methods:

We used Google Trends to extract DED-related queries estimating users' intent from 2004 to 2019 in the United States. We incorporated national climate data to generate heat maps comparing geographic, temporal, and environmental relationships of DED. Multivariable regression models were constructed to generate quadratic forecasts predicting DED and control searches.

Results:

Our results illustrated the upward trend, seasonal pattern, environmental influence, and spatial relationship of DED search volume across the US geography. Localized patches of DED interest were visualized in urban areas. There was no significant difference in DED queries across the US census regions (P = 0.3543). Regression model 1 predicted DED queries per state (R2 = 0.61), with the significant predictor being urban population [r = 0.56, adjusted (adj.) P < 0.001, n = 50]; model 2 predicted DED searches over time (R2 = 0.97), with significant predictors being control queries (r = 0.85, adj. P = 0.0169, n = 190), time (r = 0.96, adj. P < 0.001, n = 190), time2 (r = 0.97, adj. P < 0.001, n = 190), and seasonality (winter r = −0.04, adj. P = 0.0196, n = 190; spring r = 0.10, adj. P < 0.001, n = 190).

Conclusions:

Our study used Google Trends as a novel epidemiologic approach to geographically mapping the US DED. Importantly, urban population and seasonality were stronger risk factors of DED searches than temperature, humidity, sunshine, pollution, or region. Our work paves the way for future exploration of geographic information systems for locating DED and other diseases through online population metrics.