bluuebunny/crossref_metadata_2025 huggingface dataset:
Total Synthesis of (—)-Ovatolide
Authors: Delgado A , Clardy, J
Published: November 2023

Discussion Points What other isomer is formed in the nitration step a? Rationalise the regioselectivity of the mono-debenzylation reaction carried out in step b. Suggest a structure for compound 6 and give reasons for carrying out the reaction in a reductive environment. What is the mechanism of the hydrolysis of compound 8? Give an explanation for the use of ethylenediamine in step I. Further Reading For a review on diastereoselective nitroaldol reaction, see: D. Seebach, A. K. Beck, T. Mukhopadhyay and E. Thomas, Helv. Chim. Acta,1982, 65,1101. For a modification of the nitroaldol reaction using alumina, see: G. Rosini, E. Marotta, P. Righi and J. P. Seerden, J. Org. Chem.,1991, 56,6258.
Total Synthesis of RS-15385
Authors: Rohloff J C , Dyson N H , Gardner J O , Alfredson T V , Sparacino M L , III, J Robinson
Published: November 2023

Discussion Points What is the mechanism of the Bischler–Napieralski reaction of step b? Suggest a reason why less hindered bases could not be used in step f. Propose structures for the minor diastereomers obtained during the hydrogenation step g. Suggest a derivatising agent for the HPLC analysis of the optical purity of the 10-camphorsulphonic acid salt obtained in step h. Further Reading For reviews on isoquinoline alkaloids synthesis, see: M. D. Rozwadowska, Heterocycles,1994, 39,903; E. D. Cox and J.M. Cook, Chem. Rev.,1995, 95,1797. For a review on chiral derivatising agents, see: Y. Zhou, P. Luan, L. Liu and Z.-P. Sun, J. Chromatogr. B: Biomed. Appl.,1994, 659,109.
Asymmetric Synthesis of 1-Deoxy-8,8a-di-epi­ castanospermine
Authors: Martin S F , Chen H -J , Lynch, V M
Published: November 2023

Discussion Points Explain the stereoselectivity obtained in step a. Propose a mechanism for the conversion of 2 into 3. Suggest a structure for the intermediate formed in step j. Further Reading For oxidative opening of furans, see: B. M. Adger, C. Barrett, J. Brennan, M.A. McKervey and R. W. Murray, J. Chem. Soc., Chem. Commun.,1991, 21,1553. For an analysis of chelation-controlled carbonyl addition reactions, see: M. T. Reetz, Acc. Chem. Res.,1993, 26,462.
Total Synthesis of (-)-Swainsonine
Authors: Naruse M , Aoyagi S , Kibayashi, C
Published: November 2023

Discussion Points Explain the selectivity of the hetero Diels–Alder reaction of step I and suggest a reason for the lower selectivity (endo:exo 1.3:1) observed when the reaction was run in chloroform. Explain the selectivity observed in the osmylation step o. Further Reading For reviews on the use of the hetero Diels-Alder reaction in natural product synthesis, see: J. Streith and A. Defoin, Synthesis,1994, 11,1107; S. F. Martin, J. Heterocycl. Chem.,1994, 31, 619;H. Waldmann, Synthesis,1994, 6,535.
The Synthesis of (±)-Oxerine
Authors: Aoyagi Y , Inariyama T , Arai Y , Tsuchida S , Matuda Y , Kobayashi H , Ohta A , Kurihara T , Fujihira, S
Published: November 2023

Discussion Points What is the predominant reason for the selectivity of the allcylation step a? Propose a mechanism for step d. Propose a mechanism for the samarium iodide promoted cyclisation of acetylene 6. What is the reactive intermediate responsible for this step? Give reasons why the formation of cyclohexene 11 should be disfavoured. Why was it not possible to obtain alcohol 9 directly by hydroboration of olefin 7? What effect is responsible for the high diastereoselectivity observed in the methylation of ketone 8? Further Reading For a review on Baldwin’s rules, see: C. D. Johnson, Acc. Chem. Res., 1993, 26,476. For a recent review on samarium iodide, see: G. A. Molander and C.R. Harris, Chem. Rev.,1996, 96,307.
Studies Towards the Total Synthesis of Rapamycin
Authors: Anderson J C , Ley S V , Marsden, S P
Published: November 2023

Discussion Points What is the maximum theoretical yield for step a? Give a mechanism for the cyclisation step f? What is the use of PPh3 in step i? Explain the selectivity observed in step j. The anomer of 5 was found to react with lower selectivity. Suggest a reason for this finding. Propose a synthesis of vinyl iodide 8. How could the minor, undesired diastereomer obtained in the Nozaki-Kishi condensation of step n be converted into 9? Further Reading For the use of enzymes in organic solvents, see: A. L. Gutman and M. Shapira, Adv. Biochem. Eng./Biotechnol.,1995, 52,87; L. Kvittingen, Tetrahedron,1994, 50,8253; A. P. G. Kieboom, Biocatalysis,1990, 357; C.H. Wong, Science,1989, 244,1145; C. S. Chen and C. J. Sib, Angew. Chem.,1989, 101,711; A. M. Klibanov, Trends Biochem. Sci.,1989, 14,141. For a review on the preparation and reactivity of alkenyl-zinc, -copper, and -chromium organometallics, see: P. Knochel and C. J. Rao, Tetrahedron, 1993, 49,29. For a review on the Nozaki-Kishi reaction, see: P. Cintas, Synthesis, 1992, 248. For the other papers in the series, see: C. Kouklovsky, S. V. Ley and S. P. Marsden, Tetrahedron Lett.,1994, 13,2091; S. V. Ley, J. Norman and C. Pinel, Tetrahedron Lett.,1994, 35,2095.
Studies Towards the Total Synthesis of Rapamycin
Authors: Kouklovsky C , Ley S V , Marsden, S P
Published: November 2023

Discussion Points How would it be possible to recycle the undesired synisomer obtained in step a? What is the mechanism of step c? Explain the diastereoselectivity observed in the (EJ-crotylborane addition to aldehyde 4. Rationalise the diastereoselectivity observed in the epoxidation of homoallylic alcohol 5. How could the stereoselectivity of this reaction be reversed? Further Reading For an analysis of the mechanism in the oxazaborolidine catalysed reduction of ketones, see: B. Ganem, Chemtracts: Org. Chem.,1988, 1,40. For a review on enantioselective reduction of ketones, see: V. K. Singh, Synthesis,1992, 7, 607. For a review on the diastereoselectivity in nucleophilic additions to unsymmetrically substituted carbonyls, see: B. W. Gung, Tetrahedron,1996, 52,5263. For reviews on the synthesis of chiral epoxides, see: P. Besse and H. Veschambre, Tetrahedron,1994, 50,8885; W. Adam and M. J. Richter, Acc. Chem. Res.,1994, 27, 57; K. A. J rgensen, Chem. Rev.,1989, 89,431. For a review on substrate-directable reactions, see: A.H. Hoveyda, D. A. Evans and G. C. Fu, Chem. Rev.,1993, 93,1307. For a review on epoxide chemistry, see: J. Gorzynski Smith, Synthesis, 1984, 629. For a review on intramolecular reactions of allylic and propargylic silanes, see: D. Schinzer, Synthesis,1988, 4,263. For a review on the use of chiral boranes in synthesis, see: D.S. Matteson, Chem. Rev.,1986, 973.
Stereoselective Synthesis of (+)-Aromaticin
Authors: Majetich G , Song J -S , Leigh A J , Condon, S M
Published: November 2023

Discussion Points What is the mechanism of step d? Give reasons for the use of two equivalents of Lewis acid in step e. During the ene reaction of step f, a regioisomer of 6 could, in theory, be formed. Propose a structure for this isomer and suggest a reason why its formation was not observed. Explain the stereoselectivity in steps h andj. Suggest a possible reason why the phenylselenation reaction of step o required acid catalysis. Further Reading For a review on the use of silanes in the synthesis of natural products, see: E. Langkopf and D. Schinzer, Chem. Rev.,1995, 95,1375.
Synthesis of 3α-Acetoxydrimenin
Authors: Swarts H J , Verstegen-Haaksma A A , Jansen B J M , Groot, A de
Published: November 2023

Discussion Points What governs the stereoselectivity of the 1,4-addition step a? Suggest a mechanism for the rearrangement in step e? Propose a mechanism for the non-basic formylation step j? Suggest a structure for a side-product of step n caused by the basicity of theDMAP. Further Reading For the application of Criegee’s rearrangement in the synthesis of enol ethers see: R. M. Goodman and Y. Kishi, J. Org. Chem.,1994, 59,5125.
Formal Synthesis of (±)-Aphidicolin
Authors: Toyota M , Nishikawa Y , Fukumoto, K
Published: November 2023

Discussion Points The condensation step a gave a 3 : 1 mixture of isomers 2. Assuming that the stereoselectivity of the reaction can be rationalised by a Zimmerman-Traxler transition state model, what should be the structure of the predominant isomer? What is the mechanism of step b? The tetracyclic product 9 was obtained in a 3 : 1 mixture with its epimer at C5. What is the mechanism of this reaction? Rationalise the stereochemical outcome. Further Reading For a recent review of the Heck reaction see: W. Cabri and I. Candiani, Acc. Chem. Res.,1995, 28,2.
Synthetic Efforts Towards Bruceantin
Authors: Chiu C K -F , Govindan S V , Fuchs P L
Published: November 2023

Discussion Points What is the controlling factor in the stereochemical outcome of the conjugate addition of cyanide to enone 1? Based on the above fact, what would you predict the product of step c to be? Give a rationalisation for the difference in reactivity displayed by epimers 7 and 8 under basic conditions. In the transformation of ketone 11 into nitrile 12 the phenylselenyl group undergoes epimerisation. What is the driving force behind this process? Suggest a mechanism for the oxidation step u carried out in the absence of triethylamine.
Synthetic Studies on Furanoheliangolides
Authors: Brown D S , Paquette, L A
Published: November 2023

Discussion Points Suggest a mechanism for the formation of furan 2. Rationalise the stereochemical outcome of step f. The transformation 3 -> 6 involves the formal [4+2] cycloaddition of a ketene to the furan ring. Why are ketenes not usually employed directly for Diels-Alder reactions? Propose a suitable mechanism for the rearrangement of compound 14 to give the isomers 15 and 16. What role does the potassium carbonate play in the reaction? What product could be expected to be formed from the E-enol ether 17 under the conditions outlined in step r?
Total Synthesis of Staurosporine
Authors: Link J T , Raghavan S , Danishefsky, S J
Published: November 2023

Discussion Points What is the structure of the intermediate formed in step d? Suggest a reason for the closure of the oxazoline ring on the 8-face (formation of 4) and not on the a-face. Step j yielded a 2.5:1 mixture of a.:8 epoxides. Give reasons for the low stereoselectivity observed. The minor epoxide was found to react less efficiently with 2. Suggest a possible reason for this observation. The Boe protecting group on the oxazolidinone nitrogen of 10 plays a crucial role in steps x and y. Suggest the reason why it was introduced. What is the mechanism of step c’?
Instrumental and sensory analysis
Authors: Gardner Julian W , Bartlett Philip N
Published: November 2023

In this chapter we provide a brief introduction to the different techniques currently used in the evaluation of the odour and/or flavour of commercial products—including foodstuffs, beverages, perfumes, and other products. These techniques can be divided into instrumental analytical techniques and those using sensory evaluation by panels of human testers. These types of approaches are routinely used for a variety of purposes such as the development and evaluation of new products, quality control in the production of commercial products, and for evaluation and detection of taints and off-flavours. Our purpose in this chapter is to provide the reader with a general background against which the possible applications of electronic noses in these different areas can be viewed.
Data processing techniques
Authors: Gardner Julian W , Bartlett Philip N
Published: November 2023

The problem of analysing the data generated by an electronic nose (or ChemSAD) is basically one of determining the underlying relationships between one set of independent variables1 (i.e. the output from an array of n sensors) and another set of dependent variables (i.e. odour class and component concentrations). As described in Section 6.5 (p. 136), the method employed may be either an unsupervised one that seeks to discriminate between unknown odour vectors or, alternatively, it may be a supervised one in the sense that unknown odour vectors are analysed using relationships found a priori from a set of known odour vectors used in an initial calibration, learning, or training stage. Multivariate data processing, with its long history, is a well-established field that can be conveniently subdivided into two basic approaches. The first approach, which has been around since the 1960s, is statistical and in some ways is the more general and logical. Statistical multivariate analysis seeks to formulate the nature of the input data, the underlying relationships, and so the results in a probabilistic manner (Chatfield and Collins 1980). This statistical approach is sometimes referred to as parametric in that it assumes that the data can be described by a probability density function (pdf), such as a multinormal distribution. The second approach is a relatively new one that arose in the 1980s, it seeks to solve multivariate problems in a manner similar to the human cognitive process by using a biologically inspired neural construct and rules based upon human reasoning.
Biomass, energy, and environment
Authors: Ravindranath N H , Hall D O
Published: November 2023

Developing countries are searching for alternative energy options to promote sustainable and equitable development. Bioenergy, especially as a modernized fuel, is known to be an environmentally-sound energy option, but its potential and impacts need to be assessed for each developing country. The current sources, uses, and socio-economic and environmental impacts of biomass energy are analysed for India. The energy needs for development are assessed. Conventional energy planning has not led to equitable and sustainable development. Bioenergy options are shown to have potential to meet the energy needs of rural areas of a populous country like India. Case studies of successful bioenergy projects and economic analysis of bioenergy options are presented. Land is not a constraint to producing woody biomass for energy even in a densely populated country like India. Bioenergy options provide significant socio-economic benefits along with large potential for carbon-emission reduction and promotion of biodiversity in degraded lands. The potential for bioenergy is high for developing-countries of South-east Asia, Sub-Saharan Africa, and South America. There is global interest in bioenergy as a sustainable energy and green house gas emission reduction option. The Indian case study could be a model for other developing countries.
Bioenergy projects
Authors: Ravindranath N H , Hall D O
Published: November 2023

The importance of bioenergy as a modern fuel has been recognized over the past decade in industrial as well as developing countries. Attempts made in India on biomass conservation, production, and conversion to modern energy forms were broadly analysed in the previous chapter. However, there are many specific examples in India, as well as in other developing and industrial countries, of converting biomass into modern energy carriers, and it is useful here to consider some of these case studies to demonstrate the feasibility of bioenergy programmes and to learn from these experiences. The selection is basically determined by the availability of information to the authors. It is not possible to go into details of individual projects, but instead the approach adopted and performance of the projects are presented briefly. A sample of small village-level systems and large systems are considered to cover a broad spectrum.
The Biology of Rocky Shores
Authors: Little Colin , Williams Gray A , Trowbridge Cynthia D
Published: November 2023

This new edition offers a concise but comprehensive introduction to rocky shore ecology and has been completely revised and updated throughout. It describes the diverse biota (invertebrates, vertebrates, seaweeds, seagrasses and microalgae) that inhabit rocky shores, and the factors that determine their distributions, abundances and interactions. The book discusses the latest research on processes that control community structure, utilizing a global range of examples from a wide range of shore types—both temperate and tropical. The Biology of Rocky Shores begins by describing the shore environment, including the conditions caused by tidal rise and fall as well as an introduction to the effects of waves. It goes on to describe the biodiversity of the rocky shore environment, from seaweeds and cyanobacteria to starfish and oystercatchers, and some of the adaptations these organisms exhibit on the shore. The book discusses in turn the biology of primary producers, grazers, suspension feeders and predators, and the ways in which these trophic groups interact in various communities. The vertical and horizontal distributions of species in relation to the tidal cycle and wave exposure are also considered. The contributions that species make in determining how rocky-shore communities function, and how they interact with off-shore systems, are explored in detail. Human influences, notably pollution, over-fishing and the introduction of alien species, are discussed in the context of rocky shore conservation and future management strategies. A final chapter offers guidance on methods of study, techniques, and experimental approaches.
Validation of New Diagnostic Criteria (ICHD-2) For Migraine With Aura
Authors: Eriksen M K , Thomsen L L , Olesen J
Published: November 2023

Migraine with aura (MA) has been diagnosed according to the operational diagnostic criteria of the International Headache Society (ICHD-1) since 1988. The diagnosis of MA relies on the description of symptoms because there are no diagnostic bio- logical markers available. The ICHD-1 for MA was mostly based on expert opinion due to the scarcity of empirical studies. The ICHD-1 for MA was difficult to under- stand and did not describe the nature of the aura in detail.
Headache Attributed to a Substance or its Withdrawal
Authors: Silberstein S D
Published: November 2023

The International Headache Society (IHS) previously grouped medication-induced headaches under the term ‘headaches associated with substances or their withdrawal’. The new IHS classification calls them ‘headaches attributed to a sub- stance or its withdrawal’ (Table 25.1). Alcohol, food and food additives, and chemical and drug ingestion and withdrawal have all been reported to provoke or activate migraine in susceptible individuals.
Polycythaemia: a Cause of Secondary Headache?
Authors: Aamodt A H , Waage A , Stovner L J
Published: November 2023

Headache is a common symptom in conditions with polycythaemia and elevated haemoglobin levels. There are some observations indicating that elevated haemoglobin values polycythaemia may induce headache by increasing blood viscosity. In one recent population-based study, headache prevalence seems to be related to haemoglobin levels. This paper summarizes relevant reports in the literature and proposes diagnostic criteria for headache caused by polycythaemia.
Mechanisms Of Fibroblast-Mediated Joint Destruction
Authors: Pap Thomas , Gay, Renate , Gay Steffen
Published: November 2023

Rheumatoid arthritis (RA) is a chronic inflammatory disorder of yet unknown ethology that primarily affects the joints and results in the progressive destruction of articular cartilage and bone. The pathogenesis of RA involves complex changes which include the mutually interacting phenomena of chronic inflammation, altered immune responses, and synovial hyperplasia. The progressive destruction of cartilage and bone, however, represents a unique and most prominent feature of this disease. It clearly distinguishes RA from other arthritis’s and determines the outcome of disease in the majority of affected individuals. Intriguingly, there is growing evidence that the pathological mechanisms of inflammation and articular damage—although overlapping—are not identical. Rather, it has been found that joint destruction may occur even when inflammation is well controlled , and that critical steps initiating joint destruction occur very early in the course of disease3.
Examination Of The Synovium And Synovial Fluid
Authors: Tak Paul-Peter
Published: November 2023

The synovium lines the non-cartilaginous surfaces of the synovial joints and provides nutrients to avascular structures such as cartilage. Synovial tissue is also found in tendon sheaths and bursae. Since rheumatoid arthritis (RA) is an inflammatory disease that primarily targets the synovium, examination of synovial tissue might provide insight into the pathogenesis of the disease. Thus, descriptive studies of rheumatoid synovium contribute to an understanding of the events that take place in vivoand complement experimental animal studies and in vitrostudies. There has been an enormous upsurge in investigations of the pathological changes of the rheumatoid synovium because of the availability of new methods to obtain synovial biopsy specimens and because of the development of immunohistological methods, in situhybridization, the polymerase chain reaction, and microarray analysis for examination of the tissue.
Imaging In Rheumatoid Arthritis
Authors: Østergaard Mikkel , Szkudlarek, Marcin , Ejbjerg Bo Jannik
Published: November 2023

For decades, imaging in rheumatoid arthritis (RA) has been synonymous with conventional radiography (CR). However, new imaging modalities such as magnetic resonance imaging (MRI) and ultrasonography (US) have dramatically increased the information obtainable by imaging. Concurrently, an explosion in RA drug development and in data on the importance of early aggressive therapy has fuelled the search for more efficient approaches than conventional clinical and radiographical methods for diagnosis, monitoring, and prognostication of RA. Of these new approaches, MRI and US appear highly promising.
Susceptibility, Prognosis, And Mortality
Authors: Leirisalo-Repo Marjatta
Published: November 2023

Rheumatoid arthritis is a chronic systemic disease in which both environmental and genetic factors are proposed to play a role. There is evidence of a long-term immune aberration in individuals that later develop the clinical picture of rheumatoid arthritis. This is nicely demonstrated by the presence of rheumatoid factor and antifilaggrin antibodies (see Ref. 1) and anti-cyclic citrullinated peptide (anti-CCP) antibodies in asymptomatic individuals even years prior to the diagnosis of rheumatoid arthritis. However, there are a few environmental factors known to be associated with the development of the disease. Of these, smoking is the only factor strongly associated with the risk for the development of seropositive rheumatoid arthritis in several populations (see Refs 1, 3).
Systemic And Intra-Articular Glucocorticoids In Rheumatoid Arthritis
Authors: Bijlsma Johannes W J , Buttgereit, Frank , Jacobs Johannes W G
Published: November 2023

Glucocorticoids (GCs) play a pivotal role in the management of rheumatoid arthritis (RA). The proportion of patients with RA that is treated with GCs by practicing rheumatologists on a daily basis is clearly in excess of the usually cautious recommendations in textbooks and review papers. Recent studies that demonstrate disease-modifying potential of low-dose GCs in RA have renewed the debate on the risk benefit ratio with this therapy . GCs are still considered to be the most effective anti-inflammatory and immunosuppressive substances available , and our knowledge of the mechanisms of action has recently further increased.
Head and neck / ear, nose, and throat
Authors: Lund V J , Powles J , Howard D J
Published: November 2023

There are many aspects in which infection plays a part in malignant tumours of the head and neck. As the ears, nose, and throat represent collectively one of the main portals to the body, they are subject to continual assault from outside organisms. Under normal circumstances they provide a more than adequate defence through structures such as the lymphoid tissue comprising the ring of Waldeyer and physiological mechanisms such as mucociliary clearance and secretion content. However, under circumstances of genetic predisposition, immune compromise, and/or social habits such as smoking or drinking, resistance may be lowered, enabling infective agents to contribute to the development of cancer in the upper aerodigestive tract (Table 3.1). Furthermore, once malignancy has developed, a combination of malnutrition, age, and co-morbidities make these patients susceptible to secondary infection, which complicates difficult treatment, contributing to morbidity and mortality. The importance of infection in the overall prognosis of these patients cannot be overestimated.
Cancer epidemiology and prevention
Authors: Watson Dr Max , Barrett Ann , Spence Roy AJ , Twelves Chris
Published: November 2023

Cancer is a major cause of morbidity and mortality across the world. Currently in the UK one person in three will be diagnosed with cancer during their lifetime and one in four die of cancer. In the UK approximately one-quarter of a million people are diagnosed with cancer and 120,000 die each year. As 60% of all cancers are diagnosed in those aged over 65 years, our rapidly increasing older population suggests that cancer will become an even more common problem in the coming decades.
Systemic therapy: chemotherapy and biological therapy
Authors: Watson Dr Max , Barrett Ann , Spence Roy AJ , Twelves Chris
Published: November 2023

Treatment of localized disease with surgery or radiotherapy can be very effective, but most deaths from cancer are the result of metastatic disease. Systemic therapy (i.e. drugs that can treat cancer wherever it may be in the body) are therefore vitally important. Chemotherapy drugs that ‘poison’ cancer cells remain the most widely used systemic therapies, but new targeted biological therapies are becoming increasingly important. Chemotherapy still provokes strong but often misguided or inaccurate reactions from sections of the public. Such reactions are easily accessible on the internet, and many of our patients will have been exposed to such views prior to attending the clinic.
Radiotherapy
Authors: Watson Dr Max , Barrett Ann , Spence Roy AJ , Twelves Chris
Published: November 2023

Radiotherapy as a therapeutic modality developed shortly after the discovery of X-rays at the end of the nineteenth century. Clinical and technological advances subsequently have made it one of the most successful modalities in the treatment of patients with cancer, both in curative and palliative settings. ‘Radiotherapy is used for about half of the 250,000 patients who develop cancer in the UK each year. It has a curative role in two-thirds, and a palliative role in the remainder.’
Patients with lung cancer
Authors: Watson Dr Max , Barrett Ann , Spence Roy AJ , Twelves Chris
Published: November 2023

Between 10 and 20% of patients may present with, or develop complications of, the non-metastatic paraneoplastic syndromes associated with lung cancer. These are particularly well documented for small cell carcinoma and large cell undifferentiated carcinoma, both of which tend to have many neuroendocrine features. However, they do occur to a lesser degree with squamous cell carcinoma and adenocarcinoma. Many of these syndromes are mediated by peptides, which mimic active portions of known hormones.
Patients with major cancer emergencies
Authors: Watson Dr Max , Barrett Ann , Spence Roy AJ , Twelves Chris
Published: November 2023

An oncological emergency is defined as a situation arising in the cancer patient, related either to the cancer itself or its treatment, for which early diagnosis and treatment are necessary to prevent major morbidity or mortality. Optimal outcomes in these patients rely on recognition of early symptoms and signs, and institution of the appropriate therapy. Avoidance of undue morbidity and mortality is particularly important for patients in whom further treatment may significantly prolong or improve the quality of life.
Mortality, biochemistry, diet and lifestyle in rural China
Authors: Chen Junshi , Peto Richard , Pan Wenharn , Liu Boqi , Campbell T Colin , Boreham Jillian , Parpia Banoo , Cassano Patricia , Chen Zhengming , Feng Zulin , Gelband Hellen , Li Junyao , Pan Hongchao , Root Martin , Wu Yanping , Youngman Linda
Published: November 2023

This book analyses patterns in rural China in the late 1980s: patterns of causes of death, of what people ate, what they smoked and drank, what kinds of houses they lived in, what they worked at, their education, and many measurements of their blood (for cholesterol, vitamins, evidence of infectious disease) and urine (for food metabolites and other factors). The variation is examined at the level of counties scattered all over mainland China and Taiwan, representing the extremes of values for deaths from specific cancers; ie the counties with the highest and the lowest rates of lung cancer, or the highest and lowest for liver cancer. Coincidentally, this covers the extremes of many of the other variables, such as the intake of fresh fruits and vegetables, and smoking rates. The analysis that fills the pages is the correlation of all of these patterns, one variable at a time, with all the others. The question it answers is, “How well does the variation among the counties for one variable (eg cholesterol in the blood) correlate with the variation across China in deaths from different diseases (eg heart disease)?”. If the correlation is strong, it may mean that the variables are related in some causal sense, although this cannot be assumed. If the correlation is weak, it means that the variation must be caused mainly by other factors. Importantly, if the correlation is weak, it does not necessarily mean that the two variables are not related; for example, a weak correlation between blood cholesterol and deaths from heart disease does not mean that cholesterol is not implicated in heart disease, but that in China other factors are more important. Each variable page is similarly arranged, and there are keys to interpreting each element at the beginning of major sections. The book also includes numerous extra tables in the back that give mean values for many variables. These can be useful as many of these values in China are so different from the much more available and common Western values. We tend to think of the range of Western variables as somehow normal , without realizing that in China the mean value may not even be within the generally accepted normal range that we are used to.
STUDY COMPONENTS: Two surveys of mainland county mortality rates (1973-75 and 1986-88)
Authors: Chen Junshi , Peto Richard , Pan Wenharn , Liu Boqi , Campbell T Colin , Boreham Jillian , Parpia Banoo , Cassano Patricia , Chen Zhengming , Feng Zulin , Gelband Hellen , Li Junyao , Pan Hongchao , Root Martin , Wu Yanping , Youngman Linda
Published: November 2023

1. County mortality rates during the three-year period 1973-75, subdivided into a limited number of specific causes (or groups of causes), were taken from a previous nationwide study.

2. County mortality rates during the three-year period 1986-88, subdivided into many specific causes, were derived from our individual review and ICD-9 coding of 300,000 deaths. Our parallel survey of 800,000 urban deaths in 24 cities during 1986-88, conducted mainly for other purposes (Liu et al., 1998), is used in this monograph chiefly to compare rural and urban cause-specific mortality rates in mainland China. In the Annex, from page 803, cause-specific mortality rates by sex and 5-year age groups are given for urban China (24 cities), rural China (67 counties) and all China (weighted average, 0.3 urban + 0.7 rural).
Urine samples
Authors: Chen Junshi , Peto Richard , Pan Wenharn , Liu Boqi , Campbell T Colin , Boreham Jillian , Parpia Banoo , Cassano Patricia , Chen Zhengming , Feng Zulin , Gelband Hellen , Li Junyao , Pan Hongchao , Root Martin , Wu Yanping , Youngman Linda
Published: November 2023

A 12-hour urine collection was to be done in mainland China and Taiwan (from males only) on two separate days, once after a small (500 mg) oral dose of proline and once after the same dose of proline together with enough ascorbate (200 mg) to inhibit virtually all gastric nitrosation of amino acids for as long as the proline was still in the stomach. Samples of the collected urine were frozen at -15 to -20 °C prior to transport on dry ice to Beijing, and aliquots were then sent to the World Health Organisation International Agency for Research on Cancer in Lyon, France, for nitrosamine analyses. The urine was also analysed in Beijing for other factors.
Questionnaire administration, and summarised questionnaires
Authors: Chen Junshi , Peto Richard , Pan Wenharn , Liu Boqi , Campbell T Colin , Boreham Jillian , Parpia Banoo , Cassano Patricia , Chen Zhengming , Feng Zulin , Gelband Hellen , Li Junyao , Pan Hongchao , Root Martin , Wu Yanping , Youngman Linda
Published: November 2023

Local survey teams were trained to administer the questionnaires, make physical measurements, collect blood and urine samples and conduct the dietary survey. Aggregate information about the survey xiangs and villages was also gathered, through interviews with officials at the appropriate administrative levels. Two questionnaires focusing on mothers and children—although somewhat external to the main study design—were also included.

Each of the six study questionnaires is described briefly below, and the questionnaires themselves are appended (pp787-801) in the original Chinese and in English translation.
Trigeminovascular activation in cervicogenic headache
Authors: Frese A , Schilgen M , Edvinsson L , Frandsen E , Evers S
Published: November 2023

The term ‘ cervicogenic headache’ (CEH) was defined in 1983, based on clinical observations of side constant hemicrania originating from primary sources in the cervical spine. The obligatory symptom of CEH is a side-locked unilateral pain that is caused by particular movements of the cervical spine or external pressure applied to the ipsilateral neck or occipital region. Operational diagnostic criteria for CEH are proposed by The Cariogenic Headache International Study Group (CEHISG). CEH is characterized as a moderate–severe, non-throbbing, and non-lancinating pain, usually starting in the neck. There are episodes of varying duration or a fluctuating, continuous pain.
Muscular hyperalgesia in the head and orofacial area
Authors: Svensson Peter , Castrillon Eduardo , Ayesh Emad E , Cairns Brian E
Published: November 2023

The deep tissues in the head and orofacial area represent common sites for acute and chronic symptoms. For example, temporomandibular disorders (TMD) typically manifest jaw muscle pain, as well as temporomandibular joint (TMJ) sounds and neuromuscular changes reflected in limited jaw motion. The pain is often poorly localized and referred, and the jaw muscles and TMJs are often tender upon digital palpation. It has been suggested that the tenderness to palpation reflects sensitization of the peripheral or central nociceptive pathways and may be the manifestations in deep tissues of allodynia, i.e., a pain due to a stimulus which normally is not painful, and hyperalgesia, i.e., increased pain to a normally painful stimulus. This chapter briefly reviews the findings of changes in somatosensory sensitivity in experimental models of deep pain and their clinical implications.
Migrainous allodynia or triptan-induced allodynia?
Authors: Mick Gérard , Lanteri-Minet Michel , Desmeules Jules
Published: November 2023

In the last five years, several reports have unequivocally confirmed the occurrence of facial allodynia during migraine attacks in some migraines. Recent observations reveal that allodynia can also occur following systemic administration of sumatriptan. These astounding and confusing data led us to investigate the relative occurrence of the two phenomenon’s in the same population of migraineurs, and to characterize clinical features of allodynia that might be induced by oral triptans.
Allodynia and hyperalgesia Discussion summary
Authors: Ashina Messoud
Published: November 2023

The presentations, posters, and discussions during this session were devoted to mechanisms of cutaneous allodynia and muscular hyperalgesia in the cranial region. One of the important questions raised during the discussion was whether similar or different mechanisms contribute to cutaneous allodynia/hyperalgesia versus muscle allodynia/hyperalgesia. It appears that muscle may not possess the Ab fibres that have been implicated in cutaneous allodynia, yet muscle may manifest allodynia, as shown in experimental models of muscle pain in humans. Another question was how to assess allodynia in muscle. Non-painful dynamic stimulus or recoding of thermal thresholds used to assess cutaneous allodynia cannot be applied in the muscle tissue.
Cognitive control of emotion and pain in the human brain
Authors: Petrovic Predrag
Published: November 2023

When we perceive a painful stimulus it is a composite sensation including sensory – discriminative and unpleasant emotional dimensions. Pain processing is so powerful that it may stop any other ongoing neural process in the brain. However, the perception of pain is not a linear phenomenon, reflecting a signal from the peripheral neuron. Rather, the noxious input may be modulated at every level of the neural axis. One of the most potent sources of modulation lies in the brain—although these mechanisms have not been studied in great detail. However, it is well known that many of the pain regulatory processes in the brain are shared with other systems, e.g. depression, anxiety, and similar emotional disorders: therefore a deeper understanding of the how the brain can modulate pain perception may be transferred to general emotional control. Ultimately, such knowledge may help in developing new treatments for both pain and depressive/anxiety disorders. In our present research we have focused on understanding the higher cognitive processes involved in modulation of pain and emotion.
Brain imaging of allodynia and hyperalgesia
Authors: Kupers Ron
Published: November 2023

Modern brain imaging studies such as positron emission tomography (PET), functional magnetic resonance imaging (fMRI), and, more recently, magnetoencephalography (MEG) have opened exciting new avenues for the non-invasive exploration of the brain mechanisms which are at the basis of hyperalgesia and allodynia. Prior to the emergence of brain imaging techniques, our knowledge about the processing of these sensory abnormalities was based upon human psychophysical studies investigating the effects of selective nerve fiber blocks, microneurography recordings and single unit recordings in rodents, primates and man.
Brainstem and hypothalamic activation in spontaneous migraine attacks A PET study
Authors: Denuelle Marie , Fabre Nelly , Payoux Pierre , Chollet François , Geraud Gilles
Published: November 2023

For anatomical and physiological reasons, brainstem nuclei with a role both in nociception control and in cerebral vasomotricity regulation have been considered, for some twenty years now, as probably pivotal in migraine pathophysiology. A study with PET has shown an activation in some areas in the midbrain during migraine attacks. These structures could represent the putative generators of migraine attacks.
Introduction
Authors: Hayward P J
Published: November 2023

From Shetland to Scilly, the British Isles extend through 11 degrees of latitude, a distance of about 1250 km. Between eastern England and western Ireland they range through 13 degrees of longitude, about 900 km. The northern and western boundaries of this region face the open Atlantic; oceanic influences, locally modified by geographical and topographical factors, largely modulate the character of the marine environment. The eastern side of the British Isles bounds a shallow epicontinental sea; oceanic influences in the North Sea decrease towards the south, where the proximity of the European landmass has a different modifying effect. In the south, the complex hydrography of the Channel results in rapidly changing physical characteristics along its length, again with discernible environmental consequences. The Irish Sea, and major embayments such as the Bristol Channel, Liverpool Bay, the Scottish firths, and the Wash, are also characterized by particular physical conditions and, if geography is stretched to include the Channel Isles, the Gulf of St. Malo exemplifies further modifications of the marine environment. The effects of major physical factors are everywhere mediated by local geographical and topographical influences. Thus, throughout the region there exist marked gradients in the marine environment which are reflected in profuse variation in the characteristics of different marine habitats, with consequent effects on the nature of the marine fauna. Good illustrations of this have been provided by Holme (1961, 1966) and Cabioch (1968) in their studies of the environmental characteristics, bottom deposits, and benthic fauna of the Channel.
Palaeoenvironmental Context for the Late Neogene of the Turkana Basin
Authors: Feibel C S , Harris J M , Brown F H
Published: November 2023

One of the primary goals of documenting the geology and palaeontology of the Turkana Basin deposits has been to provide a broad basis upon which a reconstruction of past environments of the region can be made. The basic elements that make up such a reconstruction are palaeogeography, the depositional and post-depositional character of the sediments, and biotic indicators. The record preserved in the Turkana Basin from the past four million years provides a wealth of data from which to develop such a reconstruction.
Site-Formaticln Processes
Authors: Isaac Glynn Ll. , Isaac Barbara
Published: November 2023

In the Koobi Fora Formation most of the localities that we have designated as sites are marked as such by the presence of numerous flaked-stone artefacts, although, as reported by Henry Bunn in Chapter 8, we have also identified sites with cut-marked bones but without stone artefacts at a detectable density. The smallest concentrations of artefacts that we recognize as sites are inconspicuous clusters of a few dozen artefacts scattered within an area only 3 or 4 m in diameter (‘mini-sites’); the largest are unmistakable concentrations of several thousand artefacts and bone fragments distributed over an area that is 12−15 or more metres across (‘maxi-sites’). Previous chapters have provided reports on the individual sites and, in outline, on their contents. We now turn from the aggregate of circumstantial evidence and particular information to ask what integrated statements can be made about the behaviours, the ways of life, and the modes of adaptation of the. early hominids who made the stone artefacts. (Put in Popperian terms, what reasonable hypotheses can be tested? What potentially interesting propositions suggest themselves for testing in future work?)
The Bone Assemblages from the Excavated Sites
Authors: Bunn Henry T
Published: November 2023

More than a dozen assemblages of fossil bones, associated in most cases with stone artefacts, have been recovered from archaeological sites within the Koobi Fora Formation. These bone assemblages, along with those of equivalent age from Olduvai Gorge, constitute some of the best available evidence from the Plio-Pleistocene of hominid subsistence behaviour, in particular the consumption of meat and marrow. In this chapter I first summarize the methods of bone analysis used at Koobi Fora, then I present the basic empirical data obtained from all of the major sites, and, finally, from an archaeological and taphonomic perspective, I consider various possible interpretations of the bone assemblages. Because my principal aim here is to describe the bone assemblages in terms of the specific information they may contribute towards a better understanding of ancient hominid behaviour, I place emphasis on determining the sequence of taphonomic events, including hominid activity, that led to the accumulation of the bone assemblages and to the formation of the sites.
Locomotion and Buoyancy
Authors: Bone Q , Duvert M
Published: November 2023

Chaetognaths can produce very rapid, directed movements to catch their prey and to avoid predators, and many (perhaps most) of the pelagic species that are denser than sea water show regular brief bursts of swimming alternated with passive sinking. This rhythmic hop-and-sink pattern of activity enables them to search through the water for their prey (see Chapter 5).
Ultrastructure of subtropical crustose lichens
Authors: Tucker S C , Matthews S W , Chapman R L
Published: November 2023

Ultrastructure in thirteen species of subtropical lichens from Louisiana, USA was studied. All belong to genera prevalent in the tropics and all have trentepohliaceous photobionts. Homogeneous cross-wall ultrastructure identified Trentepohlia as photobiont in species studied of Anisomeridium, Arthonia, Pyrenula, and Trypethelium. Cephaleuros, as photobiont in the lichen Strigula complanata, has a similar homogeneous cross-wall structure, but is easily distinguished on other characteristics. A pronounced circular wall thickening around the central cluster of plasmodesmata identified Phycopeltis as photobiont in species of Anisomeridium (different to the above species), Graphis, Mazosia, Opegrapha, Porina, and Schismatomma. Previously, Graphis scripta, Schismatomma, and Anisomeridium had been reported to have Trentepohlia instead. Haustoria were present in all thirteen crustose lichen species and all had the intraparietal type (as defined by Honegger) in which the algal cell wall invaginates and surrounds the invading fungal haustorium.
Physiological ecology and evolution of the threespine stickleback
Authors: Guderley Helga E
Published: November 2023

The life cycle of the threespine stickleback exposes it to diverse physical conditions. The anadromous stickleback, in particular, faces marked changes in the salinity, temperature, and oxygenation of its environment during its annual cycle. Neuroendocrine control mechanisms and modification of tissue function provide the physiological basis of its responses to environmental changes; the physiological preparation for reproduction may influence its response to seasonal changes. For example, mobilization of somatic reserves for gonad production or parental care could accentuate the effect of high temperature on nutritional requirements and on muscle metabolic organization. Such interactions must be considered when interpreting the adaptive significance of the stickleback’s physiological responses to the environment. Common environmental signals may coordinate the reproductive cycle and adaptation to changing environmental conditions. For example, as photoperiod modifies both salinity preferences (Baggerman 1957; Audet et al. I986a) and reproductive readiness (Baggerman 1957), it is likely that these responses are mediated, at least in part, by common mechanisms.
Male Sterility Loci in Plant Mitochondrial Genomes
Authors: Hanson Maureen R , Pruitt Kirn D , Nivison Helen T
Published: November 2023

Plants lacking functional pollen are not uncommon in the plant kingdom (Laser and Lerstern, 1972). The male sterile phenotype can be inherited either as a Mendelian or cytoplasmic trait. The mitochondrial genome is presently thought to encode cytoplasmic male sterility (CMS; Leaver and Gray, 1982; Boeshore et al., 1985; Hanson and Conde, 1985; Hanson et al., 1985; Pring and Lonsdale, 1985; Newton, 1987). Analysis at the molecular level in several species has shown either that the trait segregates with the mitochondrial genome or that fertile revertants have mitochondrial genome alterations (Belliard et al., 1978; Laughnan and Gabay-Laughnan, 1983; Aviv and Galun, 1980; Clark et al., 1985; Abbott and Fauron, 1986; Rottman et al., 1987; Wise et al., 1987).