Fungal infections pose a significant threat to individuals with compromised immune systems and despite advancements in diagnosis and treatment, they continue to jeopardize patient’s health.... Show moreFungal infections pose a significant threat to individuals with compromised immune systems and despite advancements in diagnosis and treatment, they continue to jeopardize patient’s health. Maximizing the effectiveness of existing antifungal drugs is imperative. Among these, fluconazole and posaconazole are commonly prescribed to treat severe and life-threatening fungal infections. In this thesis, among others, we aimed to understand better how well different posaconazole formulations are absorbed. Through computational modeling and simulation, we learned that posaconazole is best taken with food to reduce the risk of inadequate drug absorption and subsequent therapeutic failure. This applies not only to the suspension but also to the tablet, which results in higher and more predictable absorption even though it does not achieve concentrations similar to those upon intravenous administration. Fluconazole was studied in individuals with obesity. Our findings indicate that heavier adult males may require a higher dose to achieve the desired exposure. Consequently, we proposed dosing recommendations for treating obese patients. In summary, this research, a result of the long-term collaboration between Leiden University and Radboudumc, enhanced our knowledge of factors that reduce exposure to antifungal drugs, allowing us to guide how to individualize and optimize antifungal treatment in individual patients. Show less
This article addresses some issues related to Voice and little v. It does so by discussing and analyzing the variation that exists in the Chinese language family with respect to object placement ... Show moreThis article addresses some issues related to Voice and little v. It does so by discussing and analyzing the variation that exists in the Chinese language family with respect to object placement (VO versus OV). It turns out that this variation can be accounted for straightforwardly as long as we assume, first, that Voice and v are sometimes split and sometimes bundled, even within one language, and, second, that Voice does not always select vP; it can also select VP. Show less
This dissertation investigates memorisation strategies that were employed in the fields of painting and calligraphy in imperial China, with a focus on the Ming (1368-1644) and Qing (1644-1911)... Show moreThis dissertation investigates memorisation strategies that were employed in the fields of painting and calligraphy in imperial China, with a focus on the Ming (1368-1644) and Qing (1644-1911) dynasties. Its core questions are: How do memory aids reflect the society that produced them? What role did they play in the transmission and codification of practical knowledge in the field of arts?With the expansion of the printing industry during the Ming dynasty, knowledge of artistic practices came to be valued not only by craftsmen, but also by editors, publishers and highly educated authors. By analyzing both publication context and practices of remembering recorded in works from the Ming and Qing, this study provides insight into the dynamic changes of social values attributed to crafts. It takes a socio-historical approach to analyse memory aids in textual and visual formats recorded in manuals, including formulae (jue 訣) and charts. It provides six case studies to discuss under which circumstances memory aids were composed and how they were received over time, laying a foundation for understanding how practical skills were taught and how new canons of artistic knowledge were constantly being negotiated. Show less
One long-neglected fact in linguistic research on Standard Chinese (SC) is that most speakers of SC also speak a local dialect, which may share phonological features with SC. Tonal information can... Show moreOne long-neglected fact in linguistic research on Standard Chinese (SC) is that most speakers of SC also speak a local dialect, which may share phonological features with SC. Tonal information can be a determinant of the phonological similarities or differences between some Chinese dialects and SC, yet relatively little empirical research has been conducted on the tonal system of other language varieties in Chinese aside from SC. Among these dialects, Xi’an Mandarin (XM) is particularly interesting for the seemingly simple, yet intricate mapping between its lexical tones with those in SC. In this study, the tonal systems of XM and SC were compared empirically. Tones with similar contours from XM and SC were paired, and both tone production and perception experiments were car- ried out on bidialectal speakers of XM and SC. The two experiments together showed that there is indeed systematic mapping of tones between XM and SC. The degree of similarity of the mapped tone pair in tone perception was largely dependent on the acoustic phonetic similarity between the tones in tone production, with a phonological rule playing a role in the tone pair of low contour. Show less
Situated at the crossroads of the Indian and Pacific Oceans, the Spanish Philippines offer historians an intriguing middle ground of connected histories that raises fundamental new questions about... Show moreSituated at the crossroads of the Indian and Pacific Oceans, the Spanish Philippines offer historians an intriguing middle ground of connected histories that raises fundamental new questions about conventional ethnic, regional and religious identities. This volume adds a new global perspective to the history of the Philippines by juxtaposing Iberian, Chinese and Islamic perspectives. By navigating various underexplored archival resources, senior and junior scholars from Asia, Europe and the Americas explore the diverse cultural, religious, and economic flows that shaped the early modern Philippine milieu. By zooming in from the global to the local, this book offers eleven fascinating Philippine case studies of early modern globalization. Show less
Blood for determining 25-hydroxyvitamin D-3 [25(OH)D-3] is usually obtained through venipuncture although, as an alternative for serum, dried blood spot (DBS) can be considered. The aim of this... Show moreBlood for determining 25-hydroxyvitamin D-3 [25(OH)D-3] is usually obtained through venipuncture although, as an alternative for serum, dried blood spot (DBS) can be considered. The aim of this proof-of-concept study was to investigate levels of agreement between measurements of 25(OH)D-3 obtained with DBS compared with serum. 301 Chinese participants were included who completed 25(OH)D-3 measurement from DBS and from simultaneously collected blood samples obtained by venipuncture. Measurements of both DBS and serum 25(OH)D-3 were performed using liquid chromatography followed by tandem mass spectrometry. Agreement between the two methods was assessed with Passing and Bablok regression analysis and Bland-Altman plot.Measurements showed a good correlation (Pearson's correlation coefficient r = 0.929, P < 0.001) between the two methods. After recalculating for a 13% difference, a regression equation of DBS 25(OH)D-3 = -1.91 + 1.00 serum 25(OH)D-3 was found in Passing and Bablok regression analysis. Bland-Altman analysis showed a fixed bias of 1.7 nmol/L; upper and lower limit of agreement was 24.1 nmol/L and -20.7 nmol/L, respectively.Sensitivity of recalculated DBS for 25(OH)D-3 concentrations < 30 and < 50 nmol/L was 87.8% and 91.1%, respectively, and specificity was 89.2% and 83.1%, respectively.In conclusion, a good agreement was found between the measurement of 25(OH)D-3 obtained with DBS compared with serum. DBS may possibly be used in a future screening program, but it is less suitable for individualized vitamin D status assessment. Show less
Indirectness has traditionally been viewed as commensurate with politeness and attributed to the speaker’s wish to avoid imposition and/or otherwise strategically manipulate the addressee. Despite... Show moreIndirectness has traditionally been viewed as commensurate with politeness and attributed to the speaker’s wish to avoid imposition and/or otherwise strategically manipulate the addressee. Despite these theoretical predictions, a number of studies have documented the solidarity-building and identity-constituting functions of indirectness. Bringing these studies together, Terkourafi 2014 proposed an expanded view of the functions of indirect speech, which crucially emphasizes the role of the addressee and the importance of network ties. This article focuses on what happens when such network ties become loosened, as a result of processes of urbanization and globalization. Drawing on examples from African American English and Chinese, it is argued that these processes produce a need for increased explicitness, which drives speakers (and listeners) away from indirectness. This claim is further supported diachronically, by changes in British English politeness that coincide with the rise of the individual Self. These empirical findings have implications for im/politeness theorizing and theory-building more generally, calling attention to how the socio-historical context of our research necessarily influences the theories we end up building. Show less
This thesis investigates the morpho-syntax of the aspectual system in one variety of Xiāng (namely: Chángshā), which is one of the ten sub-families of Chinese. Two of the idiosyncratic properties... Show moreThis thesis investigates the morpho-syntax of the aspectual system in one variety of Xiāng (namely: Chángshā), which is one of the ten sub-families of Chinese. Two of the idiosyncratic properties in Xiāng Chinese is that one aspect marker is used to express more than one meaning or that more than one element is used to express one aspectual meaning. I base my analysis on the assumption that inner aspect in Xiāng is a three-layered structure: Asp3P, Asp2P and Asp1P.I focus on two aspect particles, ta21 and ka41. I argue that we have two particles sharing the same morphological form: ta21PERF and ta21PROG. The difference between the two particles lies in the different syntactic positions they occupy. I also point out that ka41 should not be treated as a perfective marker. I suggest that descriptively, ka41 doubles the already existing endpoint and that it does so to make the endpoint definitive. ka41 is used to block further access to the activity preceding the lexical endpoint (for example, such event cannot be present in the progressive). I point out that in Chángshā and Xiāng in general, all three Inner aspect positions can be lexically realized. Show less
Tonal bilinguals of two closely related Chinese dialects handle two tonal systems in their mind; their two vocabularies are from closely related dialects; and they write translation equivalents... Show moreTonal bilinguals of two closely related Chinese dialects handle two tonal systems in their mind; their two vocabularies are from closely related dialects; and they write translation equivalents with common Chinese characters. Their unique language situation makes their mind special. This thesis investigates these tonal bilinguals’ lexical processing mechanism, studying how they produce and understand words. Their situation provides a valuable test case for a few important theories on bilingual lexical access. Bilingual lexical processing is flexible, influenced by the task and language mode. Moreover, compared with tonal monolinguals, these tonal bilinguals not only showed classical advantages in executive control, but sometimes even perform faster with lexical tasks. The structure of the bilingual lexicon can cause important differences in bilingual lexical processing and the corresponding functions of executive control. Show less
There is increasing evidence that non-native speech is more readily understood by listeners who share the native-language background with the speakers. Mandarin-accented English can be expected to... Show moreThere is increasing evidence that non-native speech is more readily understood by listeners who share the native-language background with the speakers. Mandarin-accented English can be expected to be better understood by Mandarin listeners than by American native listeners. The most likely reason for the effect would be that the non-native listeners fruitfully use their (intuitive) knowledge of the interfering source language (Mandarin) to classify the sounds as intended by the speaker (Cutler 2012). This phenomenon has been called the Interlanguage Speech Intelligibility Benefit (or ISIB) in its weak version (Bent & Bradlow 2003). There is also a strong version of the ISIB hypothesis which states that any non-native speaker of a language will be more intelligible to any non-native listener, simply because foreigners tend to speak more carefully and slowly than native speakers of the target language. I will draw on several published intelligibility studies, in which speakers and listeners from a wide variety of native-language backgrounds (including L1 English speakers and listeners) communicate with one another in English (Smith & Rafiqzad 1979, Bent & Bradlow 2003, Wang 2007, Van Heuven & Wang 2007, Wang & Van Heuven 2014), to assess the validity of the ISIB claim. I will show that the ISIB effect is found only occasionally and inconsistently when it is quantified in an absolute way. Generally, native listeners of the target language outperform any L2 listener, even when the L2 listener has the same mother tongue as the L2 speaker. However, if we quantify the ISIB in a relative manner, where R-ISIB is defined as the discrepancy between the actual intelligibility and the score predicted from linear addition of main effects of speaker and listener language background, the notion of interlanguage benefit begins to make more sense. It then appears that the combination of a speaker and listener who do not share the same native language suffers from a negative R-ISIB (even if one interlocutor is a native speaker of the vehicle of communication), but that any combination of speakers and listeners sharing the same mother tongue (whether L1 or L2 speakers of the vehicle of communication) show a consistently positive R-ISIB. Show less
This article discusses Malay and Chinese heritage languages as spoken in the Netherlands. Heritage speakers are dominant in another language and use their heritage language less. Moreover, they... Show moreThis article discusses Malay and Chinese heritage languages as spoken in the Netherlands. Heritage speakers are dominant in another language and use their heritage language less. Moreover, they have qualitatively and quantitatively different input from monolinguals. Heritage languages are often described in terms of change. This article focuses on three types of stability in heritage speakers: stability in form, based on two case studies on progressive and definite marking, stability in function, based on a study on classifiers in Mandarin and Cantonese Chinese, and stability in form and meaning based on a study on the non-completion of the grammaticalization process of punya. We relate (non)- change to the influence of the dominant language as well as to more general effects of bilingualism. Show less
In most languages, focus (i.e. highlighting information) is marked by modifying the melody of the sentence. But how is focus marked in a Chinese dialect with eight different citation tones and a... Show moreIn most languages, focus (i.e. highlighting information) is marked by modifying the melody of the sentence. But how is focus marked in a Chinese dialect with eight different citation tones and a complex tonal phonology?This thesis investigates the connection between tonal realization and tone change (tone sandhi) in Wenzhou Chinese, and whether and how such a connection is conditioned by prosodic structure and focus marking. Experiments were conducted with young speakers of Wenzhou Chinese, whose speech was acoustically analyzed so as to investigate the application domain of tone sandhi and the influence of focus thereon, the tonal realization on the word and phrase level and its interaction with focus, the pre-planning of sentential pitch, as well as the realization of referents with different information statuses. The experimental findings suggest that the application, but not the implementation, of tone sandhi is independent of focus, and that focus and prosodic structure have similar but independent effects on the realization of lexical tones. It is also shown that pitch scaling is sensitive to syntactic structure and complexity, and that the marking of givenness, broad focus, and narrow focus leads to discrete levels along the same acoustic parameters. These findings are of interest to researchers working on lexical tone, prosodic structure, and how information structure categories such as focus affect tonal realization and prosodic phrasing. Show less
In the first part of this study a context is set for the research, and translations of classic and modern Chinese written sources are included. In the second part I have explored the technical... Show moreIn the first part of this study a context is set for the research, and translations of classic and modern Chinese written sources are included. In the second part I have explored the technical and material aspects of Chinese painting, starting with a set of murals in three Tang tombs all dating to 706 CE. The tombs were excavated during the nineteen seventies in the Xi’an area of the central Chinese province of Shaanxi. I have collected samples of paint layers and ground layers from these tombs, and have analysed them. The study resulted in a new set of reference materials, because the data that I collected are not challenged in time or geographical location. Other paintings were however examined and compared to broaden the reach of the study. To give just one example: Works in the collection of the Freer and Sackler Gallery in Washington D.C. were included, because they are well documented in the conservation archive of the research department, which contains data that has been collected over many years and by several specialists. Show less
