Post-kala-azar dermal leishmaniasis (PKDL) drug efficacy study landscape: A systematic scoping review of clinical trials and observational studies to assess the feasibility of establishing an individual participant-level data (IPD) platform

Background: Post-kala-azar dermal leishmaniasis (PKDL) is a dermatosis which can occur after successful treatment of visceral leishmaniasis (VL) and is a public health problem in VL endemic areas. We conducted a systematic scoping review to assess the characteristics of published PKDL clinical studies, understand the scope of research and explore the feasibility and value of developing a PKDL individual patient data (IPD) platform. Methods: A systematic review of published literature was conducted to identify PKDL clinical studies by searching the following databases: PubMed, Scopus, Ovid Embase, Web of Science Core Collection, WHO Global Index Medicus, PASCAL, Clinicaltrials.gov, Ovid Global Health, Cochrane Database and CENTRAL, and the WHO International Clinical Trials Registry Platform. Only prospective studies in humans with PKDL diagnosis, treatment, and follow-up measurements between January 1973 and March 2023 were included. Extracted data includes variables on patient characteristics, treatment regimens, diagnostic methods, geographical locations, efficacy endpoints, adverse events and statistical methodology. Results: A total of 3,418 records were screened, of which 56 unique studies (n = 2,486 patients) were included in this review. Out of the 56 studies, 36 (64.3%) were from India (1983–2022), 12 (21.4%) from Sudan (1992–2021), 6 (10.7%) were from Bangladesh (1991–2019), and 2 (3.6%) from Nepal (2001–2007). Five (8.9%) studies were published between 1981–1990 (n = 193 patients), 10 (17.9%) between 1991–2000 (n = 230 patients), 10 (17.9%) between 2001–2010 (n = 198 patients), and 31 (55.4%) from 2011 onwards (n = 1,865 patients). Eight (14.3%) were randomised clinical trials, and 48 (85.7%) were non-randomised studies. The median post-treatment follow-up duration was 365 days (range: 90–540 days) in 8 RCTs and 360 days (range: 28–2,373 days) in 48 non-randomised studies. Disease diagnosis was based on clinical criterion in 3 (5.4%) studies, a mixture of clinical and parasitological methods in 47 (83.9%) and was unclear in 6 (10.7%) studies. Major drugs used for treatment were miltefosine (n = 636 patients), liposomal amphotericin B (L-AmB) (n = 508 patients), and antinomy regimens (n = 454 patients). Ten other drug regimens were tested in 270 patients with less than 60 patients per regimen. Conclusions: Our review identified studies with very limited sample size for the three major drugs (miltefosine, L-AmB, and pentavalent antimony), while the number of patients combined across studies suggest that the IPD platform would be valuable. With the support of relevant stakeholders, the global PKDL community and sufficient financing, a PKDL IPD platform can be realised. This will allow for exploration of different aspects of treatment safety and efficacy, which can potentially guide future healthcare decisions and clinical practices

Feasibility of implementing public-private mix approach for tuberculosis case management in Pokhara Metropolitan City of western Nepal: a qualitative study

BackgroundThe Public-Private Mix (PPM) approach is a strategic initiative that involves engaging all private and public health care providers in the fight against tuberculosis using international health care standards. For tuberculosis control in Nepal, the PPM approach could be a milestone. This study aimed to explore the barriers to a public-private mix approach in the management of tuberculosis cases in Nepal.MethodsWe conducted key informant interviews with 20 participants, 14 of whom were from private clinics, polyclinics, and hospitals where the PPM approach was used, two from government hospitals, and four from policymakers. All data were audio-recorded, transcribed, and translated into English. The transcripts of the interviews were manually organized, and themes were generated and categorized into 1. TB case detection, 2. patient-related barriers, and 3. health-system-related barriers.ResultsA total of 20 respondents participated in the study. Barriers to PPM were identified into following three themes: (1) Obstacles related to TB case detection, (2) Obstacles related to patients, and (3) Obstacles related to health-care system. PPM implementation was challenged by following sub-themes that included staff turnover, low private sector participation in workshops, a lack of trainings, poor recording and reporting, insufficient joint monitoring and supervision, poor financial benefit, lack of coordination and collaboration, and non-supportive TB-related policies and strategies.ConclusionGovernment stakeholders can significantly benefit by applying a proactive role working with the private in monitoring and supervision. The joint efforts with private sector can then enable all stakeholders to follow the government policy, practice and protocols in case finding, holding and other preventive approaches. Future research are essential in exploring how PPM could be optimized

Resource Allocation in Modulation and Equalization Procedures in DSL Modems (Resource-allocatie in modulatie- en egalisatie-procedures in DSL-modems)

Digital subscriber line (DSL) technology is a very popular broadband access technology. It uses the existing telephone infrastructure to provide broadband access. In order to cope with the increased bandwidth demand to support broadband services, such as, Video on Demand (VoD), real time multimedia streaming, it is important to further improve the DSL. The main performance degradation of the DSL system is caused by channel impairments, such as, crosstalk and inter-symbol interference (ISI). Furthermore, the discrete Fourier transform (DFT) based discrete multitone (DMT) system has very poor spectral properties, which prohibit the use of tones at the band edges in order to meet the power spectral density (PSD) constraints of the system, thus reducing the achievable bit rate. In order to mitigate the channel impairments as well as to combat the poor spectral properties of the DFT based DMT, sophisticated signal processing techniques are employed both in single-user DSL and multi-user DSL scenarios. These signal processing techniques increase the overall run-time complexity of the DSL system, which makes them hard to realize in practice. However, the DSL channel is a very slowly time-varying channel, which allows for offline optimization of the signal processing techniques such that their run-time complexity is reduced. This necessitates efficient algorithms to reduce the overall run-time complexity without affecting the system performance significantly. In this dissertation, various resource allocation algorithms are investigated in order to reduce the run-time complexity of the signal processing techniques without sacrificing the performance of the system. In the first part, resource allocation algorithms for the single-user DSL scenario are investigated. In particular, the per-tone pulse shaping filter based DMT transmitter and per-tone equalization (PTEQ) based DMT receiver will be considered. Owing to various properties of the DSL channel, the use of a constant number of non-zero filter taps in both the pulse shaping filter and the PTEQ is seen to unnecessarily increase the run-time complexity and hence an allocation procedure for the non-zero filter taps is called for. It can be seen that the filter tap allocation problem is a combinatorial problem. In this dissertation, we propose two approaches to reduce this combinatorial complexity: The first approach is based on a contiguous filter tap selection and the second approach is based on sparse approximation based filter design. It is shown that with both of these methods the number of required non-zero filter taps and hence the run-time complexity is reduced significantly. Furthermore, it is shown that the filter tap allocation performs even better when employed in combination with transmit power allocation. In the second part, resource allocation algorithms for the multi-user DSL scenario are investigated, where crosstalk cancellation is a crucial component. In the presence of only additive white Gaussian noise (AWGN), it has been shown that instead of performing a full so called linear zero-forcing (ZF) crosstalk cancellation only few major crosstalkers may be canceled without significant performance loss. Therefore, an optimum canceler allocation algorithm, known as partial crosstalk cancellation, only cancels the major crosstalkers per line and per tone, resulting in a significant reduction in run-time complexity. In this dissertation, we extend this partial crosstalk cancellation concept to the scenario where spatially correlated background noise is present. It is shown that in this scenario, minimum mean square error (MMSE) based cancelers outperform linear ZF cancelers. However, the optimal canceler allocation problem then has a prohibitively high complexity. In this dissertation, we propose two approaches to reduce the complexity: the first approach is based on a selection metric, which combines the information of in-domain crosstalk with information of spatially correlated background noise. Based on this selection metric the crosstalkers are ordered and selected for inclusion in the linear MMSE cancellation. This approach is then extended to include non-linear MMSE cancelers. The second approach, based on sparse approximation, directly chooses the cancelers to be taken into account by first designing a sparse linear MMSE canceler. Both of these approaches reduce the run-time complexity while performing near optimally under the resource constraint. Furthermore, it is shown that the spectrum balancing, i.e., transmit power optimization, combined with partial crosstalk cancellation further reduces the number of canceler taps required without sacrificing performance.1 Introduction 1 1.1 Broadband communication . . . . . . . . . . . . . . . 1 1.1.1 Wireline broadband technologies . . . . . . . . . . 2 1.1.2 Wireless broadband technologies .. . . . . . . . . . 4 1.2 Digital subscriber line (DSL) . . . . . . . . . . . . 6 1.3 DSL environment . . . . . . . . . . . . . . . . . . . 8 1.4 Problem statement . . . . . . . . . . . . . . . . . . 11 1.5 Thesis objective and approach . . . . . . . . . . . . 12 1.6 Thesis overview and contributions . . . . . . . . . . 13 2 Preliminaries 17 2.1 Introduction . . . . . .. . . . . . . . . . . . . . . 17 2.2 Modulation schemes . . .. . . . . . . . . . . . . . . 17 2.3 Capacity of a transmission medium . . . . . . . . . . 20 2.4 Discrete multitone modulation (DMT) . . . . . . . . . 21 2.5 DMT transmitter . . . . . . . . . . . . . . . . . . 23 2.6 DMT receiver . . . . .. . . . . . . . . . . . . . . . 25 2.7 Bit loading . . . . . . . . . . . . . . . . . . . . . 26 2.8 Power loading . . . . . . . . . . . . . . . . . . . . 27 2.9 Equalization . . . .. . . . . . . . . . . . . . . . . 29 2.10 Multi-user DSL . . . . . . . . . . . . . . . . . . . 30 2.11 Sparse approximation . . . . . . . . . . . . . . . . 36 2.12 Summary . . . . . . . . . . . . . . . . . . . . . . 37 I SINGLE-USER RESOURCE ALLOCATION 39 3 Resource allocation in a DMT transmitter with per-tone pulse shaping filters 41 3.1 Introduction . . . . . . . . .. . . . . . . . . . . . 41 3.2 System model . . . . . . . . . . . . . . . . . . . . 45 3.3 Problem formulation . . . . . . . . . . . . . . . . . 46 3.4 Resource allocation for a fixed power loading . . . . 51 3.5 Joint pulse shaping filter tap and transmit power allocation . . . . . . . . . . . . . . . . . . . . . . . 56 3.6 Simulation results . . . . . . . . . . . . . . . . . 59 3.7 Conclusion . . . . .. . . . . . . . . . . . . . . . . 63 4 Resource allocation in a DMT receiver with per-tone equalization 67 4.1 Introduction . . . . . . .. . . . . . . . . . . . . . 67 4.2 Preliminaries . . . . . . . . . . . . . . . . . . . . 69 4.3 Problem formulation . . . . . . . . . . . . . . . . . 72 4.4 Resource allocation for a fixed power loading . . . . 76 4.5 Joint equalizer filter tap and transmit power allocation . . . . . . . . . . . . . . . . . . . . . . . .80 4.6 Simulation results . . . . . . . . . . . . . . . . . 82 4.7 Conclusion . . . . . . . . . . . . . . . . . . . . . 85 5 Joint resource allocation in DMT transceivers 89 5.1 Introduction . . . . . . . . . . . . . . . . . . . . 89 5.2 System model . . . . . . . . . . . . . . . . . . . . 90 5.3 Problem formulation . . . . . . . . . . . . . . . . . 92 5.4 Resource allocation for a fixed power loading . . . . 97 5.5 Joint filter tap and transmit power allocation . . . 101 5.6 Simulation results . . . . . . . . . . . . . . . . . 103 5.7 Conclusion . . . . . . . . . . . . . . . . . . . . . 108 II MULTI-USER RESOURCE ALLOCATION 111 6 Resource allocation in multi-user crosstalk cancellation 113 6.1 Introduction . . . . . . . . . . . . . . . . . . . . 113 6.2 System model . . . . . . . . . . . . . . . . . . . . 116 6.3 MMSE-based crosstalk cancellation . . . . . . . . . 117 6.4 MMSE-based resource allocation . . . . . . . . . . . 119 6.5 Problem formulation . . . . . . . . . . . . . . . . 122 6.6 Resource allocation in linear MMSE based crosstalk cancellation . . . . . . . . . . . . . . . . . . . . . . 127 6.7 Resource allocation in MMSE-GDFE based crosstalk cancellation . . . . . . . . . . . . . . . . . . . . . . 137 6.8 Simulation results . . . . . . . . . . . . . . . . . 141 6.9 Conclusion . . . . . . . . . . . . . . . . . . . . . 144 7 Conclusions and Future Work 149 7.1 Conclusions . . . . . . . . . . . . . . . . . . . . 149 7.2 Future Work . . . . . . . . . . . . . . . . . . . . 153 Bibliography 155 Publication List 171 Curriculum vitae 173nrpages: 190status: publishe

<span style="font-size:11.0pt;font-family: "Times New Roman","serif";mso-fareast-font-family:"Times New Roman";mso-bidi-font-family: Mangal;mso-ansi-language:EN-GB;mso-fareast-language:EN-US;mso-bidi-language: HI" lang="EN-GB">Anti-leishmanial activity of <i style="mso-bidi-font-style:normal">Agave americana </i><span style="mso-bidi-font-style:italic">L.– A traditional Indian medicinal plant</span></span>

658-663<span style="font-size:11.0pt;font-family: " times="" new="" roman","serif";mso-fareast-font-family:"times="" roman";mso-bidi-font-family:="" mangal;mso-ansi-language:en-gb;mso-fareast-language:en-us;mso-bidi-language:="" hi"="" lang="EN-GB">Due to lack of safe treatment and developing resistance to the available drugs for visceral leishmaniasis or Kala-azar - a fatal parasitic disease caused by <i style="mso-bidi-font-style: normal">Leishmania donovani - the search for drugs from natural resources is imperative. In the present study, the comparative <i style="mso-bidi-font-style: normal">in vitro anti-leishmanial activity of various fractions of Agave americana extracts has been evaluated. Extracts were prepared through successive solvent extraction through Soxhlet apparatus using benzene, chloroform, ethyl acetate and methanol respectively. Among those extracts ethyl acetate fraction was capable of selectively inhibiting both stages of Leishmania donovani by generation of reactive oxygen and nitrogen species. Ethyl acetate fraction Agave americana showed significant antileishmanial activity (IC­50~25 µg/ml complete inhibition (IC90) at 50 µg/ml. This observation emphasizes the need to extend studies related to traditional medicines from botanicals for better and safe alternatives to the available anti-leishmanials.</span