早期糖尿病患者视网膜病变216例临床观察

糖尿病性视网膜病变（DR）是糖尿病的常见并发症，是一种高致盲性眼病。由于DR早期无症状而往往使患者失去最佳治疗时机，因此早发现并及时治疗具有重要意义。2002年2月～2005年10月，我们对216例早期糖尿病患者（病史5a内）进行了视网膜病变观察。现报告如下。     

吉林地区糖尿病性视网膜病变流行病学调查

目的通过对吉林地区的糖尿病人相关眼病尤其是糖尿病性视网膜病变(DR)的流行病学调查,获得吉林地区糖尿病人群中糖尿病眼病尤其是DR的发病率、诊断及治疗现状、临床干预、生活方式及其它危险因素对糖尿病眼病尤其是DR的影响。发现致盲高危人群的病因线索,从而有效降低危险因素减少致盲率,为疾病的防治提供依据。以便对吉林地区乃至东北地区糖尿病眼病进行早期干预、早期诊断、早期治疗,减轻政府及社会的负担,提高糖尿病人群生活质量。方法糖尿病就诊患者、农村患者、城市患者各占1/3进行相关检查及眼底照像,对眼底照像图片进行分析,确定糖尿病性视网膜病变临床分期,并给予诊断意见。结果 2015年1月1日至2017年4月6日共筛查糖尿病人数5 023人。其中,双眼无糖尿病性视网膜病变3 175人,糖尿病性视网膜病变人数1 648,糖尿病性视网膜病变发病率32.8%,严重非增生性糖尿病性视网膜病变人数为126人,占糖尿病性视网膜病变人数7.6%;需要行全视网膜激光光凝术治疗,增生性糖尿病性视网膜病变人数为49人,占糖尿病性视网膜病变人数3.0%,需要行视网膜激光光凝术和/或玻璃体切割手术治疗。应该进行激光治疗的右眼为121眼,左眼为98眼。实际进行激光治疗的右眼89眼,左眼82眼。眼底可见筛查人群中,有黄斑病变的病人数为704人,占糖尿病人数的14%;占糖尿病性视网膜病变人数的42.7%。结论大多数糖尿病病人没有定期检查眼底情况的意识。同时,应加强对糖尿病人群眼病知识宣教,提高糖尿病人群生活质量。     

彩超检查对糖尿病视网膜病变的临床诊断价值

目的探讨彩超检查对糖尿病性视网膜病变的诊断价值。方法彩色多普勒超声对68例2型糖尿病（DM）病人进行检查，观察并记录视网膜、玻璃体各种病理改变的位置、形态、程度、范围、活动度及视网膜中央动脉（CRA）、中央静脉（CRV）血流动力学变化情况，根据其改变的程度对观同腹埔变进行分期，许对严重增殖期手术病人进行术后结果对照证实。结果对尊尿病视网膜病变早期、增殖前期、增殖期能作出正确的分期判断。68例病人中38例（48只眼）严重增殖型视网膜病变（玻翟体登血、玻璃体机化物形成、视网膜脱离），行玻璃体视网膜切割手术，术后结果证实诊断符合率达98％。结论彩超检查糖屎病视网膜病变诊断率高，无创伤，无痛苦，可对病变进行兮期，对预后进行估测，为临床医生早期药物治疗和手术治疗的筛选提供可靠的诊断依据．     

玻璃体切除治疗糖尿病视网膜病变

玻璃体切除治疗糖尿病视网膜病变济南市第二人民医院（２００００１）王玉，卢信义糖尿病患者失明的主要原因是增殖性糖尿病性视网膜病变（ＰＤＲ）合并严重玻璃体出血、牵引性视网膜脱离和新生血管性青光眼等并发症。据Ｅｔｄｒｓ，报道。尽管对此进行了全视网膜光凝治疗...     

浅谈糖尿病视网膜病变

糖尿病是影响全身各个脏器和组织血管的糖代谢紊乱疾病,其中糖尿病视网膜病变（diabetic retinopathy,DR）为糖尿病的严重并发症之一,也是欧美各国四大致盲眼病中占第一位的眼病,眼底可表现为微动脉瘤、微静脉扩张、出血、渗出、视网膜水肿以及新生血管等改变。我们将其流行病学特点、分期、临床表现及治疗原则分别做简要介绍如下：     

合理选择中成药治疗糖尿病眼病

古代医家对糖尿病性视网膜病变（DR）没有具体记述,但已认识到消渴即为糖尿病,最终可以致盲,因此,将糖尿病性视网膜病变归属中医消渴目病的范畴。正确选择中医中药治疗糖尿病视网膜病变,可收到较好的临床疗效。     

糖尿病眼病

糖尿病眼病是糖尿病最常见的并发症之一,是当前人类致盲的主要原因。糖尿病眼病分为糖尿病视网膜病变（DR）和非视网膜眼部并发症。在1型和2型糖尿病中,糖尿病视网膜病变是特异性很高的血管并发症,病程长是重要的危险因素,患糖尿病20年后几乎所有的1型糖尿病和60％的2型糖尿病都出现不同程度的视网膜病变。DR是21～74岁人群中严重视力减退的重要原因。非视网膜眼部并发症包括白内障、青光眼和前部缺血性视神经病变。下面就糖尿病眼病研究进展综述如下。     

视网膜病变治疗不当险致盲

张大爷今年55岁，因双眼视物模糊曾于5年前就诊。矫正视力：右0．5，左0．6，眼底检查可见微血管瘤、小点片出血和硬性渗出。既往有糖尿病病史9年。确诊双眼糖尿病性视网膜病变（DR）Ⅱ期。医生建议其每3个月复诊并按时服药。两年后，张大爷因视力模糊加重第一次复诊，眼底荧光血管遣影诊断为双增殖性糖尿病性视网膜病变（PDR）Ⅳ期，建议其接受全视网膜激光光凝治疗。     

血管内皮生长因子与糖尿病视网膜病变的相关性研究

糖尿病视网膜病变（diabetic retinopathy,DR）是常见致盲眼病之一,DR的基本病理过程表现为微循环障碍,其病理特征为视网膜新生血管形成和血-视网膜屏障（blood retinal barrier,BRB）破坏。血管内皮生长因子（Vascular endothelial growth factor,VEGF）与其发生、发展密切相关,本文就VEGF与糖尿病视网膜病变的相关性的研究进展作一综述。     

早期糖尿病患者眼底病变相关因素分析

糖尿病（ＤＭ）视网膜病变（ＤＲ）是一种严重的致盲性眼病，研究早期糖尿病患者ＤＲ发病的危险因素，从而作必要的干预是非常重要的。我们对本院内分泌科住院治疗的早期糖尿病患者７２例，进行了眼科检查和相关因素的分析研究。一、对象和方法１．对象：收集１９９５年８月至１９９７年１０月本院内分泌科住院治疗的早期糖尿病患者７２例，按１９８５年ＷＨＯ诊断标准确诊，１型患者１例，２型患者７１例，男３０例，女４２例，（５９．２±９．８）岁（４０～６８岁），病程（３．２２±０．９７）年（２个月～５年）。２．方法：均作眼底…     

Андрогенный статус мужчин на фоне COVID-19

ОБОСНОВАНИЕОБОСНОВАНИЕ. COVID-19 является заболеванием, оказывающим негативное системное воздействие на организм человека, в том числе на мужские гонады. Следовательно, андрогенный статус мужчин при COVID-19 нуждается в изучении.ЦЕЛЬЦЕЛЬ. Оценить уровни общего тестостерона, глобулина, связывающего половые гормоны (ГСПГ), и свободного тестостерона у мужчин в острой фазе COVID-19 и при реконвалесценции.МАТЕРИАЛЫ И МЕТОДЫМАТЕРИАЛЫ И МЕТОДЫ. Сплошное динамическое проспективное исследование 70 мужчин со среднетяжелой и тяжелой формой COVID-19 в возрасте 50 [44; 64] лет. При проведении исследования определялись уровни общего тестостерона, ГСПГ с дальнейшим расчетом уровня свободного тестостерона по Vermeullen. Данные собирались двукратно — при госпитализации пациента и при его выписке. Статистически значимыми считали различия между группами при p<0,05.РЕЗУЛЬТАТЫРЕЗУЛЬТАТЫ. На момент госпитализации по поводу COVID-19 синдром гипогонадизма отмечался у 61 человека — 87%. Пациенты с гипогонадизмом статистически значимо не различались по возрасту и степени тяжести заболевания COVID-19 по сравнению с мужчинами без гипогонадизма. Стационарное лечение, продолжавшееся 12 [10; 14] дней, привело к статистически значимому увеличению уровней общего тестостерона с 4,7 [2,96; 8,48] до 12,85 [8,62; 19,2] нмоль/л, p<0,001; ГСПГ — с 27,87 [20,78; 36,57] до 33,76 [26,27; 52,60] нмоль/л, p<0,001 и свободного тестостерона с 107 [65; 174] до 235 [162; 337] пмоль/л, p<0,001. Это привело к устранению гипогонадизма у 28 (40%) пациентов. Пациенты с персистенцией гипогонадизма были статистически значимо старше мужчин с нормализацией тестостерона (58 [50; 74] против 45 [40; 52] лет, р<0,001), статистически значимых различий в исходных уровнях общего тестостерона, ГСПГ и свободного тестостерона выявлено не было, также не было различий в распространенности тяжелой формы COVID-19 (3,97 [2,86; 7,46] против 4,26 [2,93; 5,96] нмоль/л, p=0,100; 28,76 [20,78; 48,59] против 24,63 [18,85; 31,70] нмоль/л, р=0,994; 100 [58; 118] против 96 [64; 143] нмоль/л, p=0,522; 24 против 18%, p=0,754, соответственно).ЗАКЛЮЧЕНИЕЗАКЛЮЧЕНИЕ. COVID-19 оказывает выраженное негативное влияние на выработку тестостерона у мужчин, приводя к развитию лабораторного гипогонадизма, который является потенциально обратимым. Обратимость лабораторного гипогонадизма характерна для более молодых пациентов.     

Особенности гиперандрогении у мужчин

ОБОСНОВАНИЕ. Сегодня проблема гиперандрогении изучается преимущественно по отношению к женщинам, у мужчин этот вопрос практически не затрагивается, в то же время гиперандрогения у них может быть ассоциирована с развитием ряда заболеваний.ЦЕЛЬ. Охарактеризовать варианты физиологической гиперандрогении у мужчин.МАТЕРИАЛЫ И МЕТОДЫ. Сплошное одномоментное исследование 100 мужчин с гиперандрогенией. При проведении исследования оценивались объем и структура простаты, объем яичек; определялись уровни лютеинизирующего гормона (ЛГ), общего тестостерона, глобулина, связывающего половые гормоны (ГСПГ), с дальнейшим расчетом уровня свободного тестостерона по Vermeullen, и дигидротестостерона (ДГТ). По результатам анализа гормонального статуса пациентов с гиперандрогенией были сформированы 4 группы пациентов: 1-я — пациенты с повышенным уровнем общего тестостерона и ГСПГ; 2-я — пациенты с повышенным уровнем общего тестостерона и нормальным уровнем ГСПГ; 3-я — пациенты с повышенным уровнем общего тестостерона, ДГТ при нормальном уровне ГСПГ; 4-я — пациенты с повышенным уровнем ДГТ при нормальном уровне общего тестостерона и ГСПГ. Статистически значимыми считали различия между группами при p<0,05.РЕЗУЛЬТАТЫ. Возраст и объем простаты пациентов 1-й группы были статистически значимо выше, чем в остальных группах. Для этой группы, несмотря на высокий уровень общего тестостерона, не было характерно наличие жалоб на акне. Пациенты 2-й группы чаще жаловались на акне, но распространенность этого симптома даже в этой группе являлась статистически значимо более низкой, чем у пациентов 3-й группы. При этом частота встречаемости алопеции была статистически значимо ниже во 2-й группе, чем у пациентов как 3-й, так и 4-й групп. Пациенты 3-й группы имели самые яркие клинические проявления гиперандрогении. Для 4-й группы была характерна алопеция.ЗАКЛЮЧЕНИЕ. Повышение уровня андрогенов может выявляться в любом возрасте. При этом у мужчин старшей возрастной группы повышение уровня общего тестостерона может быть обусловлено увеличением секреции ГСПГ и не сопровождаться повышением уровня свободного тестостерона. У молодых пациентов клинические проявления гиперандрогении могут отличаться: для пациентов с повышенным уровнем ДГТ характерна андрогенная алопеция; акне характерно для мужчин с повышенным уровнем общего и свободного тестостерона, а повышение ДГТ усугубляет эту проблему.     

Molecular genotyping and frequencies of A 1 , A 2 , B, O 1 and O 2 alleles of the ABO blood group system in a Kuwaiti population

Expression of the highly polymorphic ABO gene cluster is commonly investigated for blood transfusion and analysis, but little information is available for Middle Eastern populations. This study determined the major ABO allele frequency in a Kuwaiti Arab cohort using a multiplex PCR–RFLP technique; 355 unrelated blood donors of phenotype A¹ (46), A² (31), A¹B (6), A²B (4), B (97) and O (171) were genotyped. DNA fragments of 252 (251 for O ¹ ) and 843 (842 for A ² ) bp spanning the two major exons, 6 and 7, of the ABO gene were amplified and digested with HpaII and KpnI. Thirteen different genotypes could be identified when combining the A ¹ , A ² , B, O ¹ and O ² alleles from the digestion patterns: 1 A ¹ A ¹ (0.28%), 6 A ¹ A ² (1.69%), 38 A ¹ O ¹ (10.71%), 1 A ¹ O ² (0.28%), 1 A ² A ² (0.28%), 30 A ² O ¹ (8.45%), 6 A ¹ B (1.69%), 4 A ² B (1.13%), 12 BB (3.38%), 79 BO ¹ (22.25%), 6 BO ² (1.69%), 167 O ¹ O ¹ (47.04%) and 4 O ¹ O ² (1.13%). Two of the combinations (A ² O ² , O ² O ² ) were not found. All genotypes determined were consistent with the serotypes. The frequencies of the five alleles in the Kuwaiti sample population were ABO*A¹ = 0.0746, ABO*A² = 0.0592, ABO*B = 0.1676, ABO*O¹ = 0.6831 and ABO*O² = 0.0155. These results are discussed with reference to gene frequencies reported for other ethnic groups.     

Petrographic carbon in ancient sediments constrains Proterozoic Era atmospheric oxygen levels

Oxygen concentration defines the chemical structure of Earth''s ecosystems while it also fuels the metabolism of aerobic organisms. As different aerobes have different oxygen requirements, the evolution of oxygen levels through time has likely impacted both environmental chemistry and the history of life. Understanding the relationship between atmospheric oxygen levels, the chemical environment, and life, however, is hampered by uncertainties in the history of oxygen levels. We report over 5,700 Raman analyses of organic matter from nine geological formations spanning in time from 742 to 1,729 Ma. We find that organic matter was effectively oxidized during weathering and little was recycled into marine sediments. Indeed, during this time interval, organic matter was as efficiently oxidized during weathering as it is now. From these observations, we constrain minimum atmospheric oxygen levels to between 2 to 24% of present levels from the late Paleoproterozoic Era into the Neoproterozoic Era. Indeed, our results reveal that eukaryote evolution, including early animal evolution, was not likely hindered by oxygen through this time interval. Our results also show that due to efficient organic recycling during weathering, carbon cycle dynamics can be assessed directly from the sediment carbon record.

The history of life has been interwoven with levels of atmospheric oxygen through much of Earth’s history. For example, aerobic life could only prosper after the evolution of cyanobacteria, which introduced oxygen into the environment (1). Furthermore, the oxygen requirements of aerobic eukaryotes, representing most eukaryotes by far, scale positively with their size (2). For example, mammals could not have evolved into a low-oxygen environment that was sufficient for eukaryotic microbes. In this way, the history of atmospheric oxygen has both constrained and permitted evolutionary developments requiring specific oxygen levels (3). However, fully understanding how oxygen has impacted the history of life requires reconstructing the history of atmospheric oxygen.Direct measurements of atmospheric oxygen concentration over time can be made from air trapped in glacial ice, with a record extending over the past 800,000 y (4), or in evaporitic salt, extending the record to potentially over 1 billion years (5–8). The oxygen record from ice is continuous and precise, but young, while the salt record is infrequent and requires careful screening to ensure samples are appropriate for analysis (9). Otherwise, the history of atmospheric oxygen is estimated from oxygen-sensitive proxies. Oxygen impacts the chemical nature, isotopic composition, and/or concentrations of redox-sensitive substances in the oceans (like molybdenum, e.g., refs. 10 and 11, or cerium, e.g., refs. 12 and 13) and the chemical weathering of redox-sensitive substances on land (like chromium and iron, e.g., refs. 14–16). Oxygen is also directly incorporated into sulfate during redox transformation (17). None of the proxies deriving from these processes represent a direct oxygen barometer, and each requires interpretation through modeling with a variety of assumptions regarding reaction kinetics, isotopic behavior during redox transformations, and the activity level of the ancient biosphere. These approaches are also generally hindered by a limited geologic record.Furthermore, these approaches do not provide a consensus view as to the history of atmospheric oxygen. For example, some approaches suggest maximum Mesoproterozoic Era (1,600 to 1,000 Ma) oxygen levels of 0.1 to 1% times present levels (PAL) (15, 18), whereas other approaches suggest minimum oxygen levels of 1 to 4% PAL (19–21). Also, different approaches using the same proxy can yield dramatically different results. For example, a kinetic approach to modeling cerium anomalies suggests atmospheric oxygen levels of ≤0.1% PAL from the Mesoproterozoic Era (1,600 to 1,000 Ma) through the latest Neoproterozoic Era (1,000 to 541 Ma) (13), while thermodynamic modeling of the cerium anomaly suggests oxygen levels of 1 to 2% PAL through the same time window (12). Resolving such divergent views is critical, as the Mesoproterozoic Era was a time of emerging eukaryotic ecosystems (22) whose evolution could have been influenced by oxygen availability.The carbon cycle is also impacted by oxygen in which the weatherability of ancient “geologic” organic matter is a function of oxygen concentration (23). Indeed, existing carbon cycle models suggest that considerable unweathered organic matter should be recycled into marine sediments when oxygen concentrations fall below 10% PAL (24). Thus, the extent of organic matter recycling in the geologic past yields a potential oxygen barometer. Therefore, we have explored with Raman spectroscopy nine geologic formations of relatively low thermal maturity spanning 1 billion years of the Proterozoic Eon (Table 1). We find that recycled organic matter is rare and that organic matter was oxidized during weathering as efficiently then as now, placing rather firm lower limits on levels of atmospheric oxygen through this time.Table 1.Number of sampling points and estimates of petrographic carbon concentrations

Isoelectronic perturbations to f-d-electron hybridization and the enhancement of hidden order in URu2Si2

Electrical resistivity measurements were performed on single crystals of URu_2–xOs_xSi₂ up to x = 0.28 under hydrostatic pressure up to P = 2 GPa. As the Os concentration, x, is increased, 1) the lattice expands, creating an effective negative chemical pressure P_ch(x); 2) the hidden-order (HO) phase is enhanced and the system is driven toward a large-moment antiferromagnetic (LMAFM) phase; and 3) less external pressure P_c is required to induce the HO→LMAFM phase transition. We compare the behavior of the T(x, P) phase boundary reported here for the URu_2-xOs_xSi₂ system with previous reports of enhanced HO in URu₂Si₂ upon tuning with P or similarly in URu_2–xFe_xSi₂ upon tuning with positive P_ch(x). It is noteworthy that pressure, Fe substitution, and Os substitution are the only known perturbations that enhance the HO phase and induce the first-order transition to the LMAFM phase in URu₂Si₂. We present a scenario in which the application of pressure or the isoelectronic substitution of Fe and Os ions for Ru results in an increase in the hybridization of the U-5f-electron and transition metal d-electron states which leads to electronic instability in the paramagnetic phase and the concurrent formation of HO (and LMAFM) in URu₂Si₂. Calculations in the tight-binding approximation are included to determine the strength of hybridization between the U-5f-electron states and the d-electron states of Ru and its isoelectronic Fe and Os substituents in URu₂Si₂.

The heavy-fermion superconducting compound URu2Si2 is known for its second-order phase transition into the so-called “hidden-order” (HO) phase at a transition temperature T0 ≈17.5 K. Extensive investigation of the phase space in proximity to the HO phase transition has provided a detailed picture of the electronic and magnetic structure of this unique phase (1–42). However, more than three decades after the initial characterization of URu2Si2 (1–3), the order parameter for the HO phase is still unidentified.Most perturbations to the URu2Si2 compound have the effect of suppressing HO. The application of an external magnetic field (H) suppresses the HO phase (41, 43) and many of the chemical substitutions (x) at the U, Ru, or Si sites that have been explored significantly reduce T0, even at modest levels of substituent concentration (44–52). At present, only three perturbations are known to consistently enhance the HO phase in URu2Si2: 1) external pressure P, 2) isoelectronic substitution of Fe ions for Ru, and 3) isoelectronic substitution of Os ions for Ru. Upon applying pressure P, the HO phase in pure URu2Si2 is enhanced (6) and the system is driven toward a large-moment antiferromagnetic (LMAFM) phase (53). The HO→LMAFM phase transition is identified indirectly by a characteristic “kink” at a critical pressure Pc ≈1.5 GPa in the T0 (P) phase boundary (18, 53, 54) and also directly by neutron diffraction experiments, which reveal an increase in the magnetic moment from μ ∼ (0.03±0.02)μB/U in the HO phase to μ ∼ 0.4 μB/U in the LMAFM phase (13, 55, 56).Recent reports indicate that the isoelectronic substitution of Fe ions for Ru in URu2Si2 replicates the T0(P) behavior in URu2Si2 (57–59). An increase in x in URu2−xFexSi2 enhances the HO phase and drives the system toward the HO→LMAFM phase transition at a critical Fe concentration xc ≈0.15 (58, 60). The decrease in the volume of the unit cell due to substitution of smaller Fe ions for Ru may be interpreted as a chemical pressure, Pch, where the Fe concentration x can be converted to Pch (x) (57, 59). In addition, the induced HO→LMAFM phase transition in URu2−xFexSi2 occurs at combinations of x and P that consistently obey the additive relationship: Pch(x) + Pc ≈1.5 GPa (57, 59). These results have led to the suggestion that Pch is equivalent to P in affecting the HO and LMAFM phases (58, 59).Reports of the isoelectronic substitution of larger Os ions for Ru have shown that an increase in x in URu2−xOsxSi2 1) expands the volume of the unit cell, thus creating an effective negative chemical pressure (Pch ≤0); 2) enhances the HO phase; and 3) drives the system toward a similar HO→LMAFM phase transition at a critical Os concentration of xc ≈0.065 (60–62). These results are contrary to the expectation that a negative Pch would lead to a suppression of HO and complicate the view of chemical pressure as a mechanism affecting the evolution of phases in URu2Si2.In this paper, we report on the behavior of the T(x, P) boundary for the URu2−xOsxSi2 system based on ρ(T) measurements of single crystals of URu2−xOsxSi2 as a function of Os concentration x and applied pressure P. The T(x, P) phase boundary observed here for the URu2−xOsxSi2 system (57–59) is compared to that of the URu2−xFexSi2 system and also with the behavior of T(P) in pure URu2Si2. As an explanation for the enhancement of HO toward the HO→LMAFM phase transition, we suggest a scenario in which each of the perturbations of Os substitution, Fe substitution, and pressure P favors delocalization of the 5f electrons and increases the hybridization of the uranium 5f-electron and transition metal (Fe, Ru, Os) d-electron states. To avoid an ad hoc explanation of the effect of increasing the Os concentration x in URu2−xOsxSi2, compared to the effects of pressure P and Fe substitution, we explain how pressure P, Fe substitution, and Os substitution are three perturbative routes to enhancement of the U-5f- and d-electron hybridization. The importance of the 5f- and d-electron hybridization to the emergence of HO/LMAFM is presented in the context of the Fermi surface (FS) instability that leads to a reconstruction and partial gapping of the FS during the transition from the paramagnetic (PM) phase to the HO and LMAFM phases (2, 6, 20, 22, 24–26, 37, 38, 63).In an effort to further understand the effect of isoelectronic substitution on the 5f- and d-electron hybridization, calculations in the tight-binding approximation were made for compounds from the series UM2Si2 (M = Fe, Ru, and Os). The calculations indicate that the degree of hybridization is largely dependent on the magnitude of the difference between the binding energy of the localized U-5f electrons and that of the transition metal d electrons.     

Scaling confirmation of the thermodynamic dislocation theory

The thermodynamic dislocation theory (TDT) is based on two highly unconventional assumptions: first, that driven systems containing large numbers of dislocations are subject to the second law of thermodynamics and second, that the controlling inverse timescale for these systems is the thermally activated rate at which entangled pairs of dislocations become unpinned from each other. Here, we show that these two assumptions predict a scaling relation for steady-state stress as a function of strain rate and that this relation is accurately obeyed over a wide range of experimental data for aluminum and copper. This scaling relation poses a stringent test for the validity of the TDT. The fact that the TDT passes this test means that a wide range of problems in solid mechanics, previously thought to be fundamentally intractable, can now be addressed with confidence.

For almost a century, the dislocation theory of crystalline deformation has played a central role in materials science. Unfortunately, this theory has made only modest progress for about seven decades. Although crystalline solids are essential in engineering applications and although modern experimental techniques have provided a wealth of information about dislocations in these solids, the theories developed to explain dislocation-driven phenomena have been primarily phenomenological. They describe phenomena mathematically but do not explain them; they are not predictive.The cause of this theoretical failure is clear. Dislocation-driven deformations of solids are complex nonequilibrium processes involving macroscopic numbers of dynamical degrees of freedom. Theoretical physicists know that they must use statistical methods to deal with such situations. Especially important is the second law of thermodynamics, which states that driven complex systems must move toward their most probable configurations (i.e., that their entropies must be nondecreasing functions of time). However, leading materials scientists since the 1950s have asserted that dislocation energies are too large, and that dislocation entropies are too small, for the second law to be applicable (1, 2).We have argued for a decade that those assertions are wrong. The thermodynamic dislocation theory (TDT) is based directly on the second law. It was introduced in 2010 (3) and has been shown in a series of publications since then (4–13) to be capable of solving a wide range of the most important problems in solid mechanics including strain hardening, elastic–plastic yielding, shear banding, grain-size effects, and the like. Those problems were out of reach of the conventional approaches. However, questions remain. How sure are we that the TDT is more reliable than the observation-based phenomenologies? Can we use it confidently to solve important materials problems that have been left untouched by the conventional methods?To test the reliability of the TDT, we have used it to derive a scaling law for steady-state deformations. Such scaling laws have been proposed in the past. For example, Kocks and Mecking (14) devoted much of their review article to the search for scaling relations based on experimental data and phenomenological strain-hardening formulas. The TDT-based scaling relation, however, is derived directly from first principles. As we shall show, it is accurately obeyed over a wide-enough range of experimental data to make it seem highly unlikely that there is anything fundamentally incorrect about its underlying assumptions. Our increased confidence in the TDT now leads us to raise some issues that urgently need to be addressed for both basic and applied reasons.The thermodynamic basis of the TDT has been presented in earlier publications (especially refs. 3, 7, and 9). Its main premise is that the dislocations in a deforming crystalline solid can be described—indeed, must be described—by an effective temperature Te f f that differs greatly from the ordinary, ambient temperature T. Te f f is truly a “temperature” in the conventional sense of that word; it is derived by invoking the second law of thermodynamics. It is also a true temperature in the sense that, as energy flows through an externally driven system containing dislocations, effective heat is converted to ordinary heat and dissipated. Thus, this driven, nonequilibrium system should be visualized as consisting of two weakly coupled subsystems: the dislocations at temperature Te f f and the rest of the system playing the role of a thermal reservoir at temperature T.For present purposes, we need to know only that, in steady-state shear flow, the areal density of dislocations is given by the usual Boltzmann formula:ρss=1a2 exp −eDkB Te f fss,[1]where a is a minimum spacing between dislocations, eD is a characteristic dislocation energy, and Te f fss is the steady-state effective temperature. The quantity kB Te f fss/eD, usually denoted by the symbol χ~ss, is a measure of the degree of disorder of the subsystem of dislocations. It is determined by the rate at which this subsystem is being driven at the strain rate ϵ˙. If that driving rate is slow enough that irreversible atomic rearrangements have time to relax before the strain has changed appreciably, then χ~ss must be independent of the strain rate. Typical timescales for atomic motions are of the order of 10−10s. Thus, χ~ss must be a constant for strain rates up to 106/s or even higher. It then follows from Eq. 1 that steady-state dislocation densities must also be constant across this range of driving rates, which includes most ordinary applications. In ref. 3, we used a Lindemann-like argument to estimate that χ~ss∼0.25, which turns out to be roughly correct.The second core ingredient of the TDT is the depinning (“double-exponential”) formula, which also is based on a comparison of timescales. We know that the dislocations in a deforming solid, under a wide range of circumstances, are locked together in an entangled mesh that can deform only via thermally activated depinning of pairwise junctions. The pinning times are very much longer than the times taken by dislocation segments to jump from one pinning site to another. Thus, the depinning rate controls the deformation rate, and no other rates are relevant in this approximation.To be more specific, define the depinning rate to be τP−1=τ0−1 exp[−UP(σ)/kB T], where τ0 is a microscopic timescale and UP is a pinning energy that depends on the applied stress σ. Write this energy in the form UP(σ)=kBTP exp[−σ/σT(ρ,T)], where σT(ρ,T) is a characteristic stress that determines the magnitude of σ necessary to reduce the pinning barrier by a factor of 1/e. If a′ is the separation between dislocations needed to produce this reduction and 1/ρ is the average distance between dislocations, then a′ ρ is a strain, and σT(ρ,T)=μ(T) a′ ρ is a stress, where μ(T) is the (temperature-dependent) shear modulus. In fact, σT(ρ,T) is the Taylor stress. To compute the plastic strain rate, use the Orowan formula ϵ˙pl=ρ b v, where b is the magnitude of the Burgers vector and v is the average dislocation speed 1/(τP ρ). The result isϵ˙pl=bτ0ρ exp−TPTe−σ/σT(ρ,T)[2]or equivalently,σσT(ρ,T)=−ln TTPlnϵ˙0(ρ)ϵ˙pl,[3]where ϵ˙0(ρ)≡b ρ/τ0. This is the scaling relation.For steady-state situations in which ρ=ρss remains constant, Eq. 3 contains three system-dependent but theoretically strain rate-independent parameters: σTss≡σT(ρss,T), ϵ˙0ss≡ϵ˙0(ρss), and TP. Thus, plots of measured values of σ/σTss as functions of (T/TP) ln(ϵ˙0ss/ϵ˙pl) should collapse onto a single curve after we have identified the values of those three parameters, which we can do by using known values of the modulus μ(T) and using a least-squares method to find the best fit between the parameters and the scaling curve.To check this scaling prediction, we have used a set of compression measurements by Samanta (15). These are old results, but they have the special advantage for us of using two different materials and testing them at different temperatures and strain rates under otherwise identical conditions. Our scaling graph shown in Fig. 1 contains 32 points: 12 for pure copper at three temperatures in the range (600○C to 900○C) and four strain rates (960 /s to 2,300/ s) and 20 for pure aluminum at four temperatures in the range (250○C to 550○C) and five strain rates (520 /s to 2,200 /s). Clearly, these points fall very accurately on the smooth curve predicted by the TDT analysis, which adds greatly to our confidence in this theory. The most physically interesting fitting parameters are TP=45,000 K for copper and TP=27,800 K for aluminum, which differ somewhat from previous estimates, possibly because of differing sample preparations or measurement techniques.Open in a separate windowFig. 1.Scaling relation given by Eq. 3. The solid curve is the function f(x)=ln(1/x), with x=(T/TP) ln(ϵ˙0ss/ϵ˙pl). The data points are from ref. 15 as interpreted in ref. 16.The time-dependent TDT consists of three physics-based equations of motion. The first is Hooke’s law with the (“hypo-elasto-plastic”) assumption that elastic and plastic shear rates are additive:σ˙=2 μ(1+ν) (ϵ˙tot−ϵ˙pl),[4]where ν is Poisson’s ratio and ϵ˙tot is the total elastic plus plastic strain rate. ϵ˙pl is given by Eq. 2, making this a highly nonlinear equation.Second is an equation of motion for ρ, which is a statement of energy conservation:ρ˙=κρ σ ϵ˙plγD 1−ρρss(χ~).[5]Here, γD is the dislocation energy per unit length, and κρ is the fraction of the input power σ ϵ˙pl that is converted into dislocations. The second term inside the square brackets determines the rate at which dislocations are annihilated. It does this by invoking a detailed balance approximation using the effective temperature χ~; that is, it says that the density ρ must approach the value given by Eq. 1 but with the steady-state χ~ss replaced by a time-dependent χ~ during the approach to steady-state deformation.Finally, the equation of motion for χ~ is a statement of the first law of thermodynamics:ce f f eD χ~˙=σ ϵ˙pl 1−χ~χ~ss−γD ρ˙,[6]where ce f f is the effective specific heat. The second term in the parentheses is proportional to the rate at which effective heat is converted to ordinary heat, which reminds us that χ~ is a thermodynamically well-defined temperature. Like the comparable term in Eq. 5, this is a detailed balance approximation. The last term on the right-hand side accounts for energy stored in the form of dislocations.To illustrate the solutions of these equations of motion, we show in Fig. 2 just 2 of Samanta’s 32 stress–strain datasets, compared here with the TDT predictions. The agreement between theory and experiment shown here is reassuringly excellent. Ref. 16 has details about how the TDT equations were reformulated for numerical purposes and how parameter values were chosen for comparing their predictions with the experiments. In computing the curves shown in Fig. 2, we simplified the analysis by neglecting Eq. 6 for χ~ and simply solving Eq. 5 with χ~=χ~ss=0.23, consistent with our observation in ref. 3 that χ~→χ~ss very rapidly at high temperatures T. Our measured value of χ~ss is roughly consistent with our original guess that χ~ss∼0.25. The graphs in Fig. 2 are almost identical to those shown for wider ranges of temperatures and strain rates in the early TDT papers. They also illustrate the invariance of the onset slopes for non-prehardened copper discovered experimentally by Kocks and Mecking (14) and explained theoretically in refs. 3 and 7.Open in a separate windowFig. 2.Strain hardening curves for Cu: T=1,023 K, ϵ˙=1,800/s (upper blue) and T=1,173 K, ϵ˙=960/s (lower red). The data points are from ref. 15.We emphasize that these equations of motion are based entirely on fundamental principles—the laws of thermodynamics, energy conservation, and dimensional analysis. Specific phenomena such as hardening, grain-size effects, or yielding transitions play no role in deriving them. Those phenomena are predicted by the equations. The associated physical mechanisms are contained in the derivation of the double-exponential depinning formula, Eq. 2, and in the conversion factors κρ and ce f f in Eqs. 5 and 6. For example, the extreme stress sensitivity of the strain rate in Eq. 2 naturally explains the ρ and T dependences of yield stresses; the phenomenological concept of a “yield surface” is unnecessary. In a more specific way, the physically understandable grain-size dependence of the conversion factor κρ in Eq. 5 provides a simple explanation of Hall–Petch effects. Both of these predictions are discussed in ref. 7.One of the most remarkable aspects of these results is how many ingredients of conventional dislocation theories are completely absent in this elementary version of the theory. The TDT dislocations are simply lines. We do not ask whether they are edge dislocations or screw dislocations or whether they are excess dislocations or geometrically necessary ones. There are no partial dislocations. The crystals through which they move have no specific symmetries. Their motions are unaffected by crystalline orientations, slip planes, or stacking faults. They do not undergo cross-slip. They interact with each other only at the pinning junctions and not via long-ranged elastic forces.Apparently, we can go remarkably far with only this TDT caricature, but there must be limits. Finding and understanding those limits should be a high priority for new investigations. After we see what important physics is missing, we should be able to put realistic features back into the theory in fundamentally consistent ways and thereby understand what roles they play and how important those roles may be.This process of making the TDT more realistic should help us distinguish useful phenomenological concepts from those that are unrealistic. Our candidates for the “unrealistic” category include distinctions between “mobile” and “immobile” dislocations, distinctions between different “stages” of strain hardening, and the idea that large flow stresses at high strain rates can be explained by something called “phonon drag.” At present, we see no scientific basis for any of those conventional ideas, but surely we are mistaken in some cases. We expect to learn a great deal by finding clear counterexamples or missing ingredients in the TDT.Similarly, there must be many limits to the validity of our scaling analysis. Here is an already obvious one. We have pointed out that the assumption of constant χ~ss, and thus, constant ρss, must be changed at physically plausible, high strain rates. Already, in ref. 3, we showed how a simple strain rate dependence of χ~ss with a corresponding increase in ρss can explain the high stresses observed in strong-shock experiments. We thus found agreement between TDT and experiment over 15 decades of strain rate. This kind of analysis of high strain rates was also applied in ref. 8 to interpret molecular dynamics simulations of crystalline deformation (17). We consider those simulations to have been especially important in the development of the present theory.There are many other open issues, but most of them seem to be minor technicalities in comparison with a far more important question: what is the physics of brittle and ductile fracture in crystalline solids? Basic theoretical research in this area has been at a decades-long standstill comparable with that which has afflicted theories of strain hardening.Consider the following. We know that solids are stronger when they are colder; their yield stresses and flow stresses decrease with increasing temperature. This behavior is now predicted by the TDT as seen in Eq. 2 and its applications. However, we also know that solids become more brittle (i.e., they break more easily) at lower temperatures despite the fact that they are stronger. How can these properties be consistent with each other?This basic question has not been answered. So far as we know, it is seldom even asked in the solid mechanics literature. The conventional model used for studying brittle or ductile crack initiation is one in which dislocations are emitted from infinitely sharp crack tips and move out along well-defined slip planes (18, 19). These dislocations either move freely, supposedly implying brittle behavior, or become dense enough to shield the crack tip and somehow produce ductility and toughness. Agreement with experiment is modest at best. As stated in a recent experimental paper by Ast et al. (20), an “understanding of the controlling deformation mechanism is still lacking.” Finding a predictive theory of fracture toughness in crystalline solids should now be feasible and should be a high priority for materials theorists.     

Thermal Properties of Bayfol® HX200 Photopolymer

Bayfol^® HX200 photopolymer is a holographic recording material used in a variety of applications such as a holographic combiner for a heads-up display and augmented reality, dispersive grating for spectrometers, and notch filters for Raman spectroscopy. For these systems, the thermal properties of the holographic material are extremely important to consider since temperature can affect the diffraction efficiency of the hologram as well as its spectral bandwidth and diffraction angle. These thermal variations are a consequence of the distance and geometry change of the diffraction Bragg planes recorded inside the material. Because temperatures can vary by a large margin in industrial applications (e.g., automotive industry standards require withstanding temperature up to 125°C), it is also essential to know at which temperature the material starts to be affected by permanent damage if the temperature is raised too high. Using thermogravimetric analysis, as well as spectral measurement on samples with and without hologram, we measured that the Bayfol^® HX200 material does not suffer from any permanent thermal degradation below 160°C. From that point, a further increase in temperature induces a decrease in transmission throughout the entire visible region of the spectrum, leading to a reduced transmission for an original 82% down to 27% (including Fresnel reflection). We measured the refractive index change over the temperature range from 24°C to 100°C. Linear interpolation give a slope 4.5×10−4K−1 for unexposed film, with the extrapolated refractive index at 0°C equal to n0=1.51. This refractive index change decreases to 3×10−4K−1 when the material is fully cured with UV light, with a 0°C refractive index equal to n0=1.495. Spectral properties of a reflection hologram recorded at 532 nm was measured from 23°C to 171°C. A consistent 10 nm spectral shift increase was observed for the diffraction peak wavelength when the temperature reaches 171°C. From these spectral measurements, we calculated a coefficient of thermal expansion (CTE) of 384×10−6K−1 by using the coupled wave theory in order to determine the increase of the Bragg plane spacing with temperature.     

Gas Exchange and Ventilatory Efficiency During Exercise in Pulmonary Vascular Diseases

Background and ObjectiveVentilatory inefficiency (high V′_E/V′CO₂) and resting hypocapnia are common in pulmonary vascular disease and are associated with poor prognosis. Low resting PaCO₂ suggests increased chemosensitivity or an altered PaCO₂ set-point. We aimed to determine the relationships between exercise gas exchange variables reflecting the PaCO₂ set-point, exercise capacity, hemodynamics and V′_E/V′CO₂.MethodsPulmonary arterial hypertension (n = 34), chronic thromboembolic pulmonary hypertension (CTEPH, n = 19) and pulmonary veno-occlusive disease (PVOD, n = 6) patients underwent rest and peak exercise arterial blood gas measurements during cardiopulmonary exercise testing. Patients were grouped according to resting PaCO₂: hypocapnic (PaCO₂ ≤34 mmHg) or normocapnic (PaCO₂ 35–45 mmHg). The PaCO₂ set-point was estimated by the maximal value of end-tidal PCO₂ (maximal P_ETCO₂) between the anaerobic threshold and respiratory compensation point.ResultsThe hypocapnic group (n = 39) had lower resting cardiac index (3.1 ±0.8 vs. 3.7 ±0.7 L/min/m², p < 0.01), lower peak V′O₂ (15.8 ± 3.5 vs. 20.7 ± 4.3 mL/kg/min, p < 0.01), and higher V′_E/V′CO₂ slope (60.6 ± 17.6 vs. 38.2 ± 8.0, p < 0.01). At peak exercise, hypocapic patients had lower PaO₂, higher V_D/V_T and higher P_(a-ET)CO₂. Maximal P_ETCO₂ (r = 0.59) and V_D/V_T (r = −0.59) were more related to cardiac index than PaO₂ or PaCO₂ at rest or peak exercise. Maximal P_ETCO₂ was the strongest correlate of V′_E/V′CO₂ slope (r = −0.86), peak V′O₂ (r = 0.64) and peak work rate (r = 0.49).ConclusionsResting hypocapnia is associated with worse cardiac function, more ventilatory inefficiency and reduced exercise capacity. This could be explained by elevated chemosensitivity and lower PaCO₂ set-point. Maximal P_ETCO₂ may be a useful non-invasive marker of PaCO₂ setpoint and disease severity even with submaximal effort.