Fourth Man Research Articles

Результаты реализации регионального проекта Свердловской области по скринингу и ранней диагностике онкоурологических заболеваний у мужчин (на примере рака предстательной железы).

Background. The incidence rate of oncourological diseases in the male population of Russia (including prostate cancer, PC) tends to increase. Programs aimed on the screening, early detection and on-time treatment can help to increase the cancer-specific survival (CSS) rate in the group of patients. The purpose of the study was to evaluate the results of the Sverdlovsk Oblast (SO) (Ural Federal District, Russia) Project on screening, early detection and on-time treatment of oncourological diseases (based on PC as an example) in 2005–2022. Materials and methods. This study included a review of legal documents regulating the organization of population screening and early detection of oncourological diseases (including PC) in SO. Then we systematized the outcomes of the Project in SO, including the results of screening and early detection of PC in male population, and estimation of CSS rates in patients living in the administrative districts (AD) of SO and receiving an additional medical care within the framework of the Project. Results. In 2005–2022 about 196 thousand men were assigned to the risk group for PC; every fourth man at risk group (48.7 thousand men) was additionally examined in Express Diagnostic Urological Office (EDUO) deployed in medical organizations of the 2nd (intermunicipal) level. Medical staff has detected in a timely manner about 18.5 thousand new cases of benign prostatic hyperplasia, 9.2 thousand new cases of inflammatory diseases of the urinary and genital systems, as well as 2.2 thousand new cases of oncourological diseases (including more than 1.4 thousand new cases of PC). The hazard ratio (HR) of PC death in the group of men who received additional examination under the Project was 2–3 times lower, taking into account the stage of the disease and age. Findings. The results of the Project can be used in planning regional programs for screening, early detection and on-time treatment of cancer (including PC in men).

MP30-09 ARE COMPLETE AZFc DUPLICATIONS ASSOCIATED WITH SPERMATOGENIC POTENTIAL? THE FIRST REPORTED SERIES

You have accessJournal of UrologyCME1 Apr 2023MP30-09 ARE COMPLETE AZFc DUPLICATIONS ASSOCIATED WITH SPERMATOGENIC POTENTIAL? THE FIRST REPORTED SERIES Kian Asanad, Mary Samplaski, Elena Kolomeitz, Stephen Scherer, Ryan Yuen, Christian Marshall, Kirk Lo, Ethan Grober, Brendan Mullen, Susan Lau, and Keith Jarvi Kian AsanadKian Asanad More articles by this author , Mary SamplaskiMary Samplaski More articles by this author , Elena KolomeitzElena Kolomeitz More articles by this author , Stephen SchererStephen Scherer More articles by this author , Ryan YuenRyan Yuen More articles by this author , Christian MarshallChristian Marshall More articles by this author , Kirk LoKirk Lo More articles by this author , Ethan GroberEthan Grober More articles by this author , Brendan MullenBrendan Mullen More articles by this author , Susan LauSusan Lau More articles by this author , and Keith JarviKeith Jarvi More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003258.09AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: It is well established that complete AZFc microdeletions are a common cause of male factor infertility. With advances in detection methodology, increasing cases of partial AZFc deletion and Yq duplication, especially those involving the AZFc region, have started to emerge. Here, we report the first series of infertile men with complete AZFc duplications. METHODS: Men presenting for a fertility evaluation at a single male infertility specialty clinic from 2012-2014 who had AZFc complete duplications using a targeted microarray in peripheral blood were identified. Demographics, medical, surgical, family and reproductive history, semen and hormonal parameters, as well as response to therapies were characterized. Fischer’s exact test was used to compare the rate of complete AZFc duplications in the infertile population versus fertile controls. RESULTS: We identified five men having complete AZFc duplications, which represented 4.8% (5/104) of men undergoing Y-chromosome microarray testing and 21% of men with men with AZFc abnormalities. The mean age was 33.7 years. There was a significantly higher proportion of AZFc duplications in the infertile population (5/104) vs. the fertile controls (0/148) (p= 0.013). The mean testicular volume was 18 mL. One man had a left grade 2 varicocele. The mean FSH was 5.5 IU/L (range 1-11 IU/L), LH 3.6 IU/L (range 3-4.2 IU/L), and testosterone 14.5 nmol/L (range 12.5-18.3 nmol/L). With respect to semen parameters, one man was persistently azoospermic. The second man alternated between severe oligospermia and rare non-motile sperm. The third man had one semen analysis demonstrating azoospermia and a second demonstrating a total sperm count (TSC) of 4 ×106. The fourth man was persistently oligospermic with TSCs ranging from 3.96-12.6 ×106. The fifth man had severe oligospermia, with a mean TSC of 1.5 ×106; after intervention (varicocele embolization, clomiphene citrate), his TSC rose to 21.7 ×106. He then fathered a spontaneous pregnancy. CONCLUSIONS: This is the first study to report that complete AZFc duplications are common in those infertile men with AZFc abnormalities, representing 21% of the AZFc alterations in this group. Studies only targeting AZFc deletions are underestimating the frequency of AZFc abnormalities in men with spermatogenic failure. They represent a heterogeneous group, having a variable reproductive potential. Cases should be managed on an individual basis. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e394 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kian Asanad More articles by this author Mary Samplaski More articles by this author Elena Kolomeitz More articles by this author Stephen Scherer More articles by this author Ryan Yuen More articles by this author Christian Marshall More articles by this author Kirk Lo More articles by this author Ethan Grober More articles by this author Brendan Mullen More articles by this author Susan Lau More articles by this author Keith Jarvi More articles by this author Expand All Advertisement PDF downloadLoading ...

Sex-Related Differences in Metastatic Melanoma Patients Treated with Immune Checkpoint Inhibition.

Simple SummaryImmune checkpoint inhibitors, ICI, have revolutionized the treatment of advanced melanoma. However, given the small number of patients responding to immunotherapy and the high risk for immune-related adverse events, there has been a rising interest in recent publications to identify factors that influence response to immunotherapies, including sex. We aimed at investigating sex-related differences in patients with advanced melanoma treated with ICI by linking the assessment of inflammatory response in peripheral blood, onset of IRAEs during therapy and treatment response in short- and long-term. Men with advanced melanoma showed a significantly better response to immunotherapy in short- and long-term than women. Higher immune activation in peripheral blood before and after initiation ICI might be linked to favorable treatment response during and after ICI in favor of men and decoupled from the onset of IRAEs. Given the significantly higher immunotoxicity and worse outcome experienced by women compared to men the use of ICI should be chosen carefully in women with advanced melanoma.Objectives: We aimed to investigate sex-related differences in patients with advanced melanoma treated with ICI by linking the assessment of inflammatory response in peripheral blood, onset of immune-related adverse events IRAEs during therapy and treatment response in short- and long-term. Methods: For the purpose of this single-center retrospective study metastatic melanoma patients treated with ICI were included. Baseline patient characteristics, blood sample tests and the onset of immune-related adverse events IRAEs were documented based on clinical records. The short-term treatment response was assessed with 18F-2-Fluor-2-desoxy-D-glucose Positron Emission Tomography/Computed Tomography FDG-PET/CT scans performed six months after initiation of ICI. The overall survival OS and progression-free survival PFS were used as endpoints to assess the long-term response to immunotherapy. Results: In total, 103 patients with advanced melanoma (mean age 68 ± 13.83 years) were included, 29 women (mean age 60.41 ± 14.57 years) and 74 men (mean age 65.66 ± 13.34 years). The primary tumor was located on a lower extremity in one out of three women and on the head/neck in one out of three men (p < 0.001). While the superficial spreading (41%) and nodular (36%) melanoma subtypes represented together 77% of the cases in male population, women showed a more heterogenous distribution of melanoma subtypes with the superficial spreading (35%), nodular (23%), acral lentiginous (19%) and mucosal (12%) melanoma subtypes being most frequent in female population (p < 0.001). Most differences between women and men with regards to inflammatory parameters were observed six months after initiation of ICI with a higher median NLR (p = 0.038), lower counts of lymphocytes (p = 0.004) and thrombocytes (p = 0.089) in addition to lower counts of erythrocytes (p < 0.001) and monocytes (p < 0.001) in women towards men. IRAEs were more frequent in women towards men (p = 0.013). Women were more likely to display endocrinological IRAEs, such as thyroiditis being the most frequent adverse event in women. Interestingly IRAEs of the gastrointestinal tract were the most frequent ones in men. Finally, men with advanced melanoma showed a significantly better response to immunotherapy in short- (p = 0.015) and long-term (OS p = 0.015 and PFS p < 0.001) than women. In fact, every fourth man died during the course of the disease, while every second woman did not survive. (p = 0.001). Conclusion: Men with advanced melanoma showed a significantly better response to immunotherapy in short- and long-term than women. Higher immune activation in peripheral blood before and after initiation ICI might be linked to favorable treatment response during and after ICI in favor of men and decoupled from the onset of IRAEs. Given the significantly higher immunotoxicity and worse outcome experienced by women compared to men the use of ICI should be chosen carefully in women with advanced melanoma.

Juanita Brooks's Footnote: History, Memory, and the Murder of Olivia Coombs

Juanita Brooks's Footnote: History, Memory, and the Murder of Olivia Coombs

Анализ эффективности внедрения системы скрининга остеопороза

Osteoporosis is defined as a systemic skeletal disease characterized by low mineral bone mass and microarchitectural deterioration of bone tissue. This consequently increases bone fragility and susceptibility to fracture. Osteoporosis affects every third woman and every fourth man over 50 years old. Osteoporosis is a heavy burden for the health care of the Russian Federation, defined as RUB25 billion annually. Up to 31% of women and 4% of men over 50 years of age need special therapy for prevents the destruction of bone tissue. Identification of these risk groups allows early treatment and prevention of pathological fractures. The paper analyzes modern approaches to the diagnosis of osteoporosis. An overview of diagnostic methods is given, including artificial intelligence technologies for recognizing low-energy vertebral fractures, as well as methods of routine dual-energy absorptiometry DXA. CT bone densitometry technic (QCT) are also discussed. The principle of the FRAX tool is presented to identify patients at high risk of low-energy fractures, as well as to determine the groups of patients in need of densitometric studies. Various models of osteoporosis screening are analyzed, with an assessment of their medical and economic efficiency. The economic substantiation of the most effective strategy – conducting a questionnaire on FRAX followed by densitometric studies is presented. This will prevent more than 50% of low energy fractures without increasing costs. These efforts are aimed at increasing quality of life old population. This will contribute to the achievement of the targets set in the national project “Demography”.

Metabolic characteristics, nutritional status and behavior factors in people with obesity, working at industrial plant

An obesity is the topical problem worldwide, because excessive weight is the reason of metabolic changes that lead to development of serious chronic non-communicable diseases. The examination was aimed to assess clinical and metabolic health, nutritional status and behavior risk factors of obesity in people, working at the industrial plant. Material and methods. In 348 workers of the industrial plant (210 males, 138 females) examination was performed including anthropometry: body mass index (BMI), waist and hip circumferences and their ratio, blood pressure level detection, laboratory blood tests (glucose and cholesterol levels), and questionnaire on nutritional habits and physical activity. All examined were divided in three groups depending on BMI: 1st group - 151 (43.3%) persons with normal body mass, 2nd group - 125 (36%) working people with overweight and 3rd group - 72 (20.7%) people with obesity. Results. More than half of examined workers (mostly females) had overweight or obesity with predominantly abdominal type of fat distribution and I degree. Arterial hypertension was diagnosed in 41% of all working people (predominantly I degree), more frequently observed in obese (62.5%) and in males (45%). Each fourth man and woman had elevated total cholesterol level, which increased depending on BMI raise. Postprandial hyperglycemia was observed in 5.5% of cases, with the same frequency in both genders, predominantly in obesity. A significant part of responded with obesity, especially females, confirmed, that the reasons of excessive weight were stresses and somatic diseases (37%), and they preferred chocolate from confectionery. It was noted a correlation of BMI with egg consumption in males and with the consumption frequency of nuts, seeds and chocolate in females. Physical activity less than 3 times a month or never was observed in most of responded workers with overweight and obesity (73%), especially in males, as well as in females during the last month before the survey (57%). Conclusion. Preventive examination detected not only high prevalence of abdominal obesity, arterial hypertension and fat metabolism disturbances in people, working at the industrial plant, but also allowed to detect the most significant alimentary and behavioral risk factors of obesity.

Psychoemotional stress as a risk factor for reproductive health disorders

Introduction. Currently, the factors that affect male reproductive health are not well understood. The aim of study is to research the risk factors for male reproductive health disorders. Materials and methods. The study was an online test, the software of which is implemented using a specially developed data processing and storage scheme, as a separate page of the site. The study included questions related to marital status, level of education, lifestyle, a block of questions related to work, and also used standardized questionnaires: Hospital Anxiety and Depression Scale (HADS), diagnosis of stress (A.O. Prokhorov), questionnaire on the symptoms of aging in men (SAM), international index of erectile function (IIEF-5). Results. The results of the study showed that every second man has signs of androgen deficiency, and every fourth man has erectile dysfunction, despite the fact that the majority of respondents are less than 45 years old. Conclusions. The relationship between the presence of stress, depression and androgen deficiency was revealed, which significantly increases the risk of male reproductive health disorders.

The Spectral Arctic: A History of Dreams&amp;Ghosts in Polar Exploration, by Shane McCorristine

Reviewed by: The Spectral Arctic: A History of Dreams & Ghosts in Polar Exploration by Shane McCorristine Hester Blum (bio) The Spectral Arctic: A History of Dreams & Ghosts in Polar Exploration, by Shane McCorristine; pp. x + 265. London: University College London Press, 2018, £40.00, £22.99 paper, $75.00, $45.00 paper. At the end of his legendary Endurance expedition, Ernest Shackleton traversed the mountains of South Georgia Island toward a whaling station, where he and his crew were eventually rescued. But during the grueling march—in which he and two crew members covered thirty-two miles in thirty-six hours—the British explorer found that they were not alone: “during that long and racking march. . . . it seemed to me often that we were four, [End Page 680] not three . . . I said nothing to my companions on the point, but afterwards Worsley said to me, ‘Boss, I had a curious feeling on the march that there was another person with us.’ Crean confessed to the same idea” (South [Macmillan, 1920], 211). Where did the unaccountable phantom fourth man come from? Shane McCorristine’s The Spectral Arctic: A History of Dreams & Ghosts in Polar Exploration offers some compelling answers. Exploring the ghosts, spirits, and clairvoyant figures that populate the British imaginary of the northern polar regions throughout the nineteenth century and in some present instances, The Spectral Arctic shares Shackleton’s sense (albeit through a focus on the Arctic, not the South) that a record of polar journeying would be “incomplete” without a reckoning of the “intangible” figures that populate the Arctic and Antarctic dreamscape (South, 211). McCorristine is interested in Arctic forms of “dreaming, clairvoyante travel, reverie, spiritualism and ghost-seeing” (3). In his account, dream encounters became a way for a larger Anglo-American public to engage with a region to which few white Westerners traveled in the period. Although he devotes some attention to Inuit shamanistic practices and spiritual beliefs, McCorristine focuses most on the rippling cultural effects of the lost Northwest Passage expedition launched by Briton John Franklin in 1845. The missing two ships were sought publicly and intensely for decades afterward, and information about the 129 missing men was scant. (Both ships were located on the Canadian Arctic seafloor only very recently, in 2014 [Erebus] and 2016 [Terror].) Dreams, mesmeric communication, fantasy, and other forms of spectral or supranatural intelligence filled the informational void. This is a fresh and provocative new approach to polar expeditionary history, and to the voyaging stories often told. The Spectral Arctic is populated by fascinating figures such as Emma L., the “Seeress of Bolton” (87). Emma was a servant to an apothecary and surgeon who found her “vulgar” and “ignorant,” yet she discovered that she could gather information and travel great distances—clairvoyantly—after he subjected her to heavy doses of ether (88). Emma felt the Arctic chill and spoke to Franklin; she was sickened by drinking fish oil in imitation of the missing man. Her clairvoyant abilities caught the attention of Franklin’s wife and niece, who further sought mesmeric communication with the absent commander. McCorristine might have explored further the ways in which gender inflects mesmeric practice and reception, as many of his primary examples are women, including the American spirit rapper Margaret Fox, who was Philadelphian and Arctic explorer Elisha Kent Kane’s lover. The chapter in The Spectral Arctic devoted to feminized emotions and “polar queen[s]” is directed more toward romantic images of women than to the function of gender in mesmeric power (177). McCorristine’s definition of the spectral in this book is broad. His interest is not in secular disenchantment, but instead in the “cultural production of the spectral,” or conversation between present and past occurring across Anglo-American receptions of polar expeditionary narratives (43). This provides him with a rich body of material from which to draw, and he brings illuminating attention to little-discussed moments in nineteenth-century expeditionary accounts, such as the significance of various methods of walking, rambling, or desultory perambulating performed in the Arctic regions, whether by the Inuit or the Britons. And yet at times the book gives the impression that ghosts, enchantment, and spectrality are just other...

‘The trouble with treachery nowadays’: Revisiting the Age of Treason in Philby, Burgess and Maclean and Blunt

The Cambridge spy ring has been the subject of many dramatic representations on British television. While prior scholarship has largely focused on plays by Dennis Potter and Alan Bennett depicting the later lives of such figures, this article examines an alternative tradition: representations which re-enact events at the height of their careers in the early Cold War. I focus on two productions which centre specifically on events surrounding the 1951 defection of Guy Burgess and Donald Maclean, but from hugely contrasting perspectives. Firstly, Philby, Burgess and Maclean (ITV, 1977) by Ian Curteis covers a ten-year period from the 1945 ‘Volkov Incident’ to Kim Philby's exoneration in 1955. This production closely adheres to broadly accepted accounts of the case as known in the late 1970s, and I examine this is as a product of the public service-oriented drama-documentary culture of Granada Television. I then contrast this with the revised narrative presented in Robin Chapman's Blunt (BBC, 1987). Not only does this incorporate the newly revealed ‘fourth man’, Anthony Blunt, but it also offers a more humanised portrayal of Burgess and centres much of its drama on the marginal but implicated figure of Goronwy Rees. I explore how, in contrast to Curteis, Chapman takes greater artistic licence in examining the spies' personal lives, which resulted in a wave of controversy. I argue that this portrayal can be situated within a broader revisionist school of 1980s representation which mobilised these icons of an earlier generation's ideals in order to critique new political developments.

Towards prevention of metastatic prostate cancer: recent molecular insights from the direct analysis of metastatic precursor cells

Metastasis is the major cause of cancer-related deaths in patients with solid cancers (1). Prostate cancer (PC) is the second most frequently diagnosed cancer in males, detected in about every fourth man, and the fifth leading cause of death in men worldwide (2). Somehow surprisingly, the 5-year survival rate of M0-stage patients (i.e., patients without evidence of distant metastasis) is close to 100% (1), because PC is very slowly progressing. The growth of metastasis often takes more than 10 years and death due to metastasis frequently occurs more than 15 years after diagnosis (3,4). Consequently, most men die with PC, not due to PC.

Abdominal wall hernias—A local manifestation of systemically impaired quality of the extracellular matrix

Throughout life, inguinal hernia develops in approximately every fourth man, some of whom develop multiple hernias. If patients at risk of developing multiple hernias could be identified by a serologic biomarker, treatment might be able to be tailored and improved. Evidence suggests that abdominal wall hernia formation is associated with altered collagen metabolism. The aim of this study was to evaluate biomarkers for type IV and V collagen turnover in patients with multiple hernias and control subjects without hernia. Venous blood was collected from 88 men (mean age, 62years) with a history of more than 3 hernia repairs and 86, age-matched men without hernias. Biomarkers for synthesis of collagen type IV (P4NP) and type V (P5CP) as well as breakdown (C4M and C5M) were measured in serum by validated, solid-phase, competitive assays. Collagen turnover was indicated by the ratio between the biomarker for synthesis and breakdown. Type IV collagen turnover was 1.4-fold increased in patients with multiple hernias compared to control subjects (P<.001), whereas type V collagen turnover was 1.7-fold decreased (P<.001). Diagnostic power of P5CP was 0.83 (95%C.I.:0.77-0.89), P<.001. Patients with multiple hernias exhibit increased turnover of type IV collagen and a decreased turnover of type V collagen, demonstrating systemically altered collagen turnover. Biomarkers for type V collagen turnover may be used to identify patients at risk for or with multiple hernias.

Ultrazvuk abdomena i male karlice na nivou primarne zdravstvene zaštite

Ultrasound exam of abdomen and pelvis is performed routinely in primary health care institutions by radiologists, subspecialist in ultrasound diagnosis and GP specialists who are trained ehosonographers. The aim of this study is to determine which are the most common findings in these ultrasound examinations. Results indicate that in about one-third of exams there is no echomortfopathology, or there only incidentally discovered isolated microlithiasis of kidney, which has no particular clinical significance. In second place is the liver steatosis, usually associated with moderate or significant hepatomegaly, which is seen in about every fifth patient. Also, every fourth man has enlarged prostate. In approximately 11% exams, or roughly at every tenth patient, renal cysts were observed. Similar incidence is verified for nephrolithiasis, with measurable renal stones. One among 14 patients has a gallbladder stone or stones (about 7% of the examined). About 9% of women, or nearly every 10th women on the exam has findings on the internal genitals (myomas, ovarian cysts, endometrial atypical appearance, fluid in Douglas pouch, pregnancy ...). About 18,5% of the examined patinets have other less frequent findings.

Sickness absence and self-reported health a population-based study of 43,600 individuals in central Sweden

BackgroundSickness absence is very high in Sweden. The reasons for this phenomenon are not well known. The aim of this study was to investigate the association between degree of self-reported sickness absence and health. The hypothesis was that individuals with long-term sickness absence would report more symptoms and lower self-rated health. Another hypothesis was that women are more likely to self-rate psychiatric diagnoses compared to men, who are more likely to self-rate musculoskeletal diagnoses.MethodsThe data was obtained with a postal survey questionnaire answered by 43,589 individuals, a Swedish random population sample of men and women aged 18–84 years. The response rate was 65%. This study included 19,826 individuals aged 18–64 years old and still at work. They were divided into four groups, based on the number of reported days of sickness absence during the past year.ResultsApproximately 40% of the individuals at work mentioned that they had been absent due to illness sometime during the past year. Of those who had been absent 90 days or more, two thirds were women. There was a significant difference between the groups in self-rated health (p < 0.05). Every fifth woman (19.4%) and every fourth man (25.9%) in the group with a sickness absence of more than 89 days rated their health as poor or very poor, but a large proportion, 43.5% of the women and 31.6% of the men, rated their health as good. Long-term illnesses and complaints differed between the groups. The correlations between the groups and illness were mostly significant (p < 0.01). Two thirds of the subjects had both psychiatric and musculoskeletal symptoms. There was a significant difference among them, as men more often had musculoskeletal diagnoses. One third had only psychiatric or musculoskeletal symptoms and in those groups there were no significant diagnosis differences between the sexes.ConclusionIndividuals with long-term sickness absence reported more symptoms and lower self-rated health than did those who had not been absent at all, and than those who had been ill 1–28 days. Men and women sick-listed 29 days or more generally reported more illness and complaints. No sex differences among psychiatric and musculoskeletal diagnoses were found, but when reported both psychiatric and musculoskeletal symptoms the musculoskeletal diagnoses were significant among men.

A Nation at Risk and the Blind Men

ONCE upon a time, there lived six blind men in a faraway country. They were revered as leaders, and one day the villagers said to them, need in this land. The six men, having no idea what this reform was, decided to set about finding out. of them went to where the lived, grabbed hold of a portion, and described what seemed most salient about it. Lo, is a way to catch the public's attention and help us get elected, said the man who wanted to further his political agenda. No! Education means educating citizens to support democratic values, said the man who lived on a $3-million houseboat. Oh, no! means all students must learn basic skills and how to follow directions, said the man who owned the factories. Not at all, said the fourth man, a strong believer in testing. It is a chance to test children at least twice a year, and the more tests the better. We can finally hold teachers accountable. No! is an opportunity to garner some state revenue by selling tests for teachers and students, said the fifth man, who was a test-maker. You're all wrong! is a way to make sure all children learn what they need to know. will create academic equality, said the sixth man, who was an academician. Then they began to argue about reform, and every one of them insisted that he was right. They were growing agitated, when a wise man was passing by and heard the commotion. he had learned the cause of their troubles, the wise man calmly explained, All of you are right, and all of you are wrong. THE PARADOXES IN EDUCATION Like the six blind men, every part of the land of reacted differently to A Nation at Risk. And during the rest of the 1980s and 1990s, that report spawned an outpouring of other reports on various aspects of education. Some saw the problem as bad teachers, which immediately raised the question of bad schools of education where they were trained. Today, a similar perception is at least partly responsible for the surge in alternative teacher certification programs that has been taking place over the past 25 years. Other observers--even some members of the panel that wrote A Nation at Risk--saw the problem as low standards. Their subsequent labors led to the development of what came to be known as the standards movement--a broad enough term to encompass the efforts of the individual disciplines to set out a body of knowledge and skills in each field along with the efforts of those who pushed for high school graduation exams, which are now facts of life in the majority of states. With regard to the disciplinary standards, Diane Ravitch said in a 2006 interview, When they [the standards standards documents] are overwhelming in bulk, they can't be taken seriously. Then they are just a wish list. The jury is still out on the high school graduation tests, though concerned observers such as Anne Wheelock in Massachusetts have been collecting and analyzing data on school dropouts before ninth grade. (1) Nor was higher exempt from criticism in A Nation at Risk, though, as an institution, it has proved less willing to go along with the various proposals that spun off from the original report than has K-12 education. …

The Appearance of a Hero

The Appearance of a Hero (in four unequal parts) Peter Levine (bio) [Begin Page 75] By young I mean twenty-three. By easy I mean the circumstances of my life at the time, by which I mean working five days a week and six hours a day at a job that paid me a great deal of money for little more than terrific hustle and a college degree and very good luck. By beautiful I mean the setting, which was a country club, which was summertime, which was four men in a parking lot beside a cobalt-blue Ferrari 612 Scaglietti, bugs lofted up and knocking against the lamps, this country club in the middle of thirty acres of mowed grass and a golf course, a dozen tennis courts and an Olympic-sized pool, a palatial clubhouse with frescoed ceilings and gold-leafed chandeliers and views of wide lawns so green you felt at times you were drowning. By evil, I mean the fourth man. [End Page 75] Young By young I mean possessing very little responsibility. By young, I mean that when I was folded into the doubles group at that country club, I was treated kindly but patronizingly at first, until the three men, all in their forties, with whom I played discovered that I was good, called the lines fairly and consistently, listened to them politely when they went on about work, which was, respectively: lawyering, orthodontics and economics. So, the men I played with. The lawyer—dark-haired and short, a smile that made you want to smile, a mouth so filthy that when he joked you were not sure whether to be offended or laugh. The lawyer's name was Jeff. The orthodontist, then: giant, a former UCLA defensive end, hands so large I could not believe that he was able to get them into people's mouths, had grown up poor, I suspected, but had done very well, had two offices in the suburbs, one in the city, had a terrific, flat serve resulting from his size but was unable to move to the net quickly, also resulting from his size. His name was Will. The professor, then, our Hero, wholly sweet and warm, came to my defense when I first joined that foursome—said that they'd a ringer on their hands, he was sure of it, he could tell by my gait, and I said I wasn't that good, it'd been forever since I'd played. And Will, the orthodontist, asked me, as we stretched out on the soft-turf courts in the beginning of the summer, if I'd ever played tennis with a Nobel Prize winner. I said I had not. Jeff, the lawyer, said that when you win the Nobel Prize, your ego is not the only thing to increase, and we all laughed, and the professor, an economist at the University of Chicago, said not to pay these guys any attention, that they were glad I was playing with them, they needed some young blood. The professor—the prizewinner—his name was Walter. He took me on as his partner that first evening. I very much admired his way. There was a rise of earth just beyond the courts, and one could see, sometimes, deer shuffling in between the trees. One could hear, always, in the evening, crickets. One could hear, if it was about to rain, their noise quicken and drive up, the static in the air smelling good, and then perhaps a vein of lightning, and we'd go inside the clubhouse and have drinks. So young, which meant I was faster than the other three, and they treated me the way men treat someone who is older than their sons but younger than their brothers. They were all three married. They all three had children. [End Page 76] Among the things we spoke of while drinking beer out of frosted mugs at the clubhouse, having visited the steam room and showered and smelling good and clean: the women tennis pros, asses so tight they looked unreal, and Jeff, the lawyer, would say that he would give anything to be the tennis ball stuffed...

Crafting Information Technology Governance

The Blind Men and the Elephant (Saxe, 1872) retells an ancient Indian fable of six blind men who visit the palace of the Rajah and encounter an elephant for the first time. The first blind man put out his hand and touched the side of the elephant: “How smooth, an elephant is like a wall.” The second blind man put out his hand and touched the trunk of the elephant: “How round, an elephant is like a snake.” The third blind man put out his hand and touched the tusk of the elephant: “How sharp, an elephant is like a spear.” The fourth blind man put out his hand and touched the leg of the elephant: “How tall, an elephant is like a tree.” The fifth blind man reached out his hand and touched the ear of the elephant: “How wide, an elephant is like a fan.” The sixth blind man put out his hand and touched the tail of the elephant: “How thin, an elephant is like a rope.”

Deficiencies in the essential Smp3 mannosyltransferase block glycosylphosphatidylinositol assembly and lead to defects in growth and cell wall biogenesis in Candida albicans.

Glycosylphosphatidylinositols (GPIs) are essential for viability in yeast and have key roles in cell wall construction. Assembly of Saccharomyces cerevisiae GPIs includes the addition of a fourth, side-branching mannose (Man) to the third Man of the core GPI glycan by the Smp3 mannosyltransferase. The SMP3 gene from the human pathogenic fungus Candida albicans has been cloned. CaSMP3 complements the inviable S. cerevisiae smp3 null mutant and, when expressed in an S. cerevisiae smp3/gpi13 double mutant, it permits in vivo conversion of the Man3-GPI precursor that accumulates in that mutant to a Man4-GPI. One allele of CaSMP3 was disrupted using the ura-blaster procedure, then the remaining allele was placed under the control of the glucose-repressible MAL2 promoter. Repression of CaSMP3 expression leads to accumulation of a GPI precursor glycolipid whose glycan headgroup contains three mannoses and bears a phosphodiester-linked substituent on its first Man. Under repressing conditions, cells exhibited morphological and cell wall defects and became inviable. CaSmp3p therefore adds a fourth, alpha1,2-linked Man to trimannosyl GPI precursors in C. albicans and is necessary for viability. Because addition of a fourth Man to GPIs is of less relative importance in mammals, Smp3p is a potential antifungal target.

The Essential Smp3 Protein Is Required for Addition of the Side-branching Fourth Mannose during Assembly of Yeast Glycosylphosphatidylinositols

The major glycosylphosphatidylinositols (GPIs) transferred to protein in mammals and trypanosomes contain three mannoses. In Saccharomyces cerevisiae, however, the GPI transferred to protein bears a fourth, alpha1,2-linked Man on the alpha1,2-Man that receives the phosphoethanolamine (EthN-P) moiety through which GPIs become linked to protein. We report that temperature-sensitive smp3 mutants accumulate a GPI containing three mannoses and that smp3 is epistatic to the gpi11, gpi13, and gaa1 mutations, which normally result in the accumulation of Man(4)-GPIs, including the presumed substrate for the yeast GPI transamidase. The Smp3 protein, which is encoded by an essential gene, is therefore required for addition of the fourth Man to yeast GPI precursors. The finding that smp3 prevents the formation of the Man(4)-GPI that accumulates when addition of EthN-P to Man-3 is blocked in a gpi13 mutant suggests that the presence of the fourth Man is important for transfer of EthN-P to Man-3 of yeast GPIs. The Man(3)-GPI that accumulates in smp3 is a mixture of two dominant isoforms, one bearing a single EthN-P side branch on Man-1, the other with EthN-P on Man-2, and these isoforms can be placed in separate arms of a branched GPI assembly pathway. Smp3-related proteins are encoded in the genomes of Schizosaccharomyces pombe, Candida albicans, Drosophila melanogaster, and Homo sapiens and form a subgroup of a family of proteins, the other groups of which are defined by the Pig-B(Gpi10) protein, which adds the third GPI mannose, and by the Alg9 and Alg12 proteins, which act in the dolichol pathway for N-glycosylation. Because Man(4)-containing GPI precursors are normally formed in yeast and Plasmodium falciparum, whereas addition of a fourth Man during assembly of mammalian GPIs is rare and not required for GPI transfer to protein, Smp3p-dependent addition of a fourth Man represents a target for antifungal and antimalarial drugs.

Insulin resistance and intima-media thickness in the carotid and femoral arteries of clinically healthy 58-year-old men. The Atherosclerosis and Insulin Resistance Study (AIR).

To examine whether insulin resistance was associated with ultrasound-assessed measures of atherosclerosis in men with varying degrees of obesity. A random selection of subjects from the general population were divided into quintiles of a body mass index/blood glucose score that was shown to be a valid and reproducible index of the degree of insulin sensitivity as assessed by the clamp technique. Every fourth man in quintiles 1 and 5 and every 20th man in quintiles 2-4 (in total, 104 men) were selected for an ultrasound examination of the carotid and femoral arteries and a euglycaemic hyperinsulinaemic clamp examination, adjusted for fat-free mass. A university hospital. A total of 104 clinically healthy 58-year-old men of Swedish ancestry. The mean common carotid artery intima-media thickness (IMT), but not the common femoral IMT, correlated significantly with glucose infusion rate (GIR) (r = - 0.20, P < 0.05), systolic blood pressure (r = 0.20, P < 0.05), pulse pressure (r = 0.23 P < 0.01), heart rate (r = 0.20, P < 0.05), HDL cholesterol (r = - 0.18, P < 0.05), log triglycerides (r = 0.28, P < 0.01), apoA1 (r = - 0.20, P < 0.05), apoB (r = 0.21, P < 0.05), LDL particle size (r = - 0.22, P < 0.05) and plasma insulin (r = 0.20, P < 0.05). In a multiple regression, common carotid IMT was independently associated with log triglycerides (beta = 0.25, P = 0.012) and pulse pressure (beta = 0.21, P = 0.031) (R2 = 8.7%, P = 0.005) Insulin sensitivity, measured with the gold standard euglycaemic hyperinsulinaemic clamp method, showed similar associations with ultrasound-assessed measures of atherosclerosis in the carotid arteries as established cardiovascular risk factors, but only triglycerides and pulse pressure contributed independently to the variability in the common carotid intima-media thickness.

Glycosylphosphatidylinositol Anchors Represent the Major Carbohydrate Modification in Proteins of Intraerythrocytic Stage Plasmodium falciparum

The nature and extent of carbohydrate modification in intraerythrocytic stage Plasmodium falciparum proteins have been controversial. This study describes the characterization of the carbohydrates in intraerythrocytic P. falciparum proteins and provides an overall picture of the nature of carbohydrate modification in the parasite proteins. P. falciparum strains were metabolically labeled with radioactive sugar precursors and ethanolamine at different developmental stages. The individual parasite proteins separated on SDS-polyacrylamide gels and whole parasite cell lysates were analyzed for the carbohydrate moieties. The results established the following: 1) glycosylphosphatidylinositol (GPI) anchors represent the major carbohydrate modification in the intraerythrocytic stage P. falciparum proteins; 2) in contrast to previous reports, O-linked carbohydrates are either absent or present only at very low levels in the parasite; and 3) P. falciparum contains low levels of N-glycosylation capability. The amount of N-linked carbohydrates in whole parasite proteins is approximately 6% compared with the GPI anchors attached to proteins based on radioactive GlcN incorporated into the proteins. The glycan cores of multiple parasite protein GPI anchors are all similar, consisting of protein-ethanolamine-phosphate-(Manalpha1-2)6Manalpha1-2M analpha1-6Ma nalpha1- 4GlcN. The fourth Man residues distal to GlcN of the GPI anchor glycan cores contain unidentified substituents that are susceptible to conditions of nitrous acid deamination. This unusual structural feature may contribute to the reported pathogenic properties of the P. falciparum GPI anchors.