Methods for improvement of informal settlement in Kabul City, Afghanistan

Afghanistan witnessed rapid urbanization in recent decades due to the post-war recovery process. When the war ended in 2001 by the fall of Taliban regime, most of Afghans refugees returned back to urban areas of Afghanistan especially in Kabul city. Moreover, the rapid urbanization, migration from rural areas and population growth impacted on Kabul city with the manifestation of informal settlement. Informal settlement in Kabul city refers to the housing and settlement which built up in violation of the master plan of Kabul city. The problems of the informal settlement are considerable challenges to the informal residents and government. Thus, this research aims to investigate the identification of methods for improvement of the informal settlement in District 13 of Kabul city. In order to reach the aim of the research, field survey interview has been conducted with 22 Afghan government officials, and questionnaire survey has been conducted with 200 residents of District 13 of Kabul city. The gathered data includes both qualitative data and quantitative data. The content analysis has been used to analyze qualitative data, and the frequency analysis has been used to analyze the quantitative data. The finding on the built environment problems posed by informal settlement in District 13 are lack of drainage system and sewage system, lack of solid waste management, unpaved narrow street, lack of open spaces, recreation and greenery, lack of water supply and pollution of underground water. Moreover, different factors leading to growth of informal settlement are rapid increase of population, and limited capacity of government. Finally, through the resident’s preferences, government capacity, and District 13 physical condition, the research suggests three methods which can be used for the improvement of the informal settlement in District 13 of Kabul city which is settlement upgrading as the first option, the land readjustment as the second option and urban redevelopment as the last option. This research is essential and has significance for the government of Afghanistan and the informal residents, through enhancing the information and awareness of the government officials towards the need, preferences and most problems of informal settlements

Manual Scalp Cooling in Early Stage Breast Cancer: Value of Caretaker Training and Patient-Reported Experience to Optimize Efficacy and Patient Selection

Title: Manual scalp cooling in early stage breast cancer: value of caretaker training and patient-reported experience to optimize efficacy and patient selection Authors: Manaz Rezayee1, BS Nicole Moxon1, RN Staci Mellinger1, RN Amanda Y. Seino1 Nicole E. Fredrich1 Tracy L. Kelly1 Susan Mulligan2, MA Patrick Rossi3, MD Ijeoma Uche1, MD Walter J. Urba1, MD PHD Alison K. Conlin1, MD MPH Janet Ruzich1, DO David B. Page1, MD Background: Alopecia is an emotionally distressing common adverse effect of curative-intent chemotherapy in early stage breast cancer.1–6 Although machine-based scalp cooling is effective for reduction of chemotherapy-associated alopecia in early stage breast cancer, availability is geographically limited.7–11 Manual cold-cap systems may also be effective and are available regardless of geographic location.12–14 We evaluated the feasibility of caretaker-administered cold-cap efficacy following structured standardized training, and utilized patient-reported subjective outcomes to develop a clinical tool to facilitate patient selection. Patients and Methods: A small pilot study (n=10) was conducted to evaluate the feasibility and efficacy of manual cold capping. Key eligibility criteria included: 1) no hair loss at baseline; 2) no pre-existing scalp condition; 3) planned curative-intent chemotherapy for early stage breast cancer and 4) availability of caretaker(s). Participants received standardized training and then performed the cold-cap procedure without assistance. The primary endpoint was post-treatment hair retention using Dean’s alopecia scale, with success defined as Results: Of the evaluable patients, 80% (n=8/10) met the primary efficacy endpoint (Dean’s scale 0-2) with 20% (n=2/10) trial failures due to pre-mature discontinuation. Manual cold-capping was worthwhile to 90% of patients (Was it Worth It? Questionnaire) and associated with favorable PROs. Patient interviews identified a number of themes shared by almost all patients, which were subsequently used to develop a questionnaire to aid patient-directed decision-making on whether to pursue manual cold-capping. Conclusion: This study affirms the safety and efficacy of manual cold-capping to reduce alopecia and demonstrates the importance of proper training and education to maximize efficacy. It also highlights the considerable costs and effort associated with cold-capping. Selected patients with early stage breast cancer may benefit subjectively from cold capping while the proposed clinical instrument can be used to facilitate an informed discussion between patient and provider.https://digitalcommons.psjhealth.org/cancer_institute_fellowships/1000/thumbnail.jp

Massive rearrangements of cellular MicroRNA signatures are key drivers of hepatocyte dedifferentiation

Hepatocytes are dynamic cells that, upon injury, can alternate between nondividing differentiated and dedifferentiated proliferating states in vivo . However, in two‐dimensional cultures, primary human hepatocytes (PHHs) rapidly dedifferentiate, resulting in loss of hepatic functions that significantly limits their usefulness as an in vitro model of liver biology, liver diseases, as well as drug metabolism and toxicity. Thus, understanding the underlying mechanisms and stalling of the dedifferentiation process would be highly beneficial to establish more‐accurate and relevant long‐term in vitro hepatocyte models. Here, we present comprehensive analyses of whole proteome and transcriptome dynamics during the initiation of dedifferentiation during the first 24 hours of culture. We report that early major rearrangements of the noncoding transcriptome, hallmarked by increased expression of small nucleolar RNAs, long noncoding RNAs, microRNAs (miRNAs), and ribosomal genes, precede most changes in coding genes during dedifferentiation of PHHs, and we speculated that these modulations could drive the hepatic dedifferentiation process. To functionally test this hypothesis, we globally inhibited the miRNA machinery using two established chemically distinct compounds, acriflavine and poly‐l ‐lysine. These inhibition experiments resulted in a significantly impaired miRNA response and, most important, in a pronounced reduction in the down‐regulation of hepatic genes with importance for liver function. Thus, we provide strong evidence for the importance of noncoding RNAs, in particular, miRNAs, in hepatic dedifferentiation, which can aid the development of more‐efficient differentiation protocols for stem‐cell‐derived hepatocytes and broaden our understanding of the dynamic properties of hepatocytes with respect to liver regeneration. Conclusion: miRNAs are important drivers of hepatic dedifferentiation, and our results provide valuable information regarding the mechanisms behind liver regeneration and possibilities to inhibit dedifferentiation in vitro

Pandemic Vulnerability Knowledge Visualisation for Strategic Decision-Making: A COVID-19 Index for Government Response in Australia

Purpose: This study aims to develop a pandemic vulnerability knowledge visualisation index to support the strategic decision-making efforts of authorities. Design/methodology/approach: First, the key vulnerability factors from the literature are identified. Second, using the vulnerability factors as indicators, a composite index is developed. Last, from the index values, a set of vulnerability knowledge maps, showing the vulnerability hotspots, are prepared. Findings: Ten indicators are identified as vulnerability factors that could significantly impact the virus spread risks. Verifying the identified hotspots against the recorded infected cases and deaths has evidenced the usefulness of the index. Determining and visualising the high-vulnerability locations and communities could help in informed strategic decision-making and responses of the authorises to the pandemic. Originality/value: The study demonstrates that the developed pandemic vulnerability knowledge visualisation index is particularly appropriate in the context of Australia. Nonetheless, by replicating the methodologic steps of the study, customised versions can be developed for other country contexts. Keywords: knowledge visualisation; strategic decision-making; community vulnerability; COVID-19; government response; Australia Paper type: Research paper</p

Feasibility to use whole-genome sequencing as a sole diagnostic method to detect genomic aberrations in pediatric B-cell acute lymphoblastic leukemia

IntroductionThe suitability of whole-genome sequencing (WGS) as the sole method to detect clinically relevant genomic aberrations in B-cell acute lymphoblastic leukemia (ALL) was investigated with the aim of replacing current diagnostic methods.MethodsFor this purpose, we assessed the analytical performance of 150 bp paired-end WGS (90x leukemia/30x germline). A set of 88 retrospective B-cell ALL samples were selected to represent established ALL subgroups as well as ALL lacking stratifying markers by standard-of-care (SoC), so-called B-other ALL.ResultsBoth the analysis of paired leukemia/germline (L/N)(n=64) as well as leukemia-only (L-only)(n=88) detected all types of aberrations mandatory in the current ALLTogether trial protocol, i.e., aneuploidies, structural variants, and focal copy-number aberrations. Moreover, comparison to SoC revealed 100% concordance and that all patients had been assigned to the correct genetic subgroup using both approaches. Notably, WGS could allocate 35 out of 39 B-other ALL samples to one of the emerging genetic subgroups considered in the most recent classifications of ALL. We further investigated the impact of high (90x; n=58) vs low (30x; n=30) coverage on the diagnostic yield and observed an equally perfect concordance with SoC; low coverage detected all relevant lesions.DiscussionThe filtration of the WGS findings with a short list of genes recurrently rearranged in ALL was instrumental to extract the clinically relevant information efficiently. Nonetheless, the detection of DUX4 rearrangements required an additional customized analysis, due to multiple copies of this gene embedded in the highly repetitive D4Z4 region. We conclude that the diagnostic performance of WGS as the standalone method was remarkable and allowed detection of all clinically relevant genomic events in the diagnostic setting of B-cell ALL

Oligodendrocyte heterogeneity in the mouse juvenile and adult central nervous system

Oligodendrocytes have been considered as a functionally homogeneous population in the central nervous system (CNS). We performed single-cell RNA sequencing on 5072 cells of the oligodendrocyte lineage from 10 regions of the mouse juvenile and adult CNS. Thirteen distinct populations were identified, 12 of which represent a continuum from Pdgfra(+) oligodendrocyte precursor cells (OPCs) to distinct mature oligodendrocytes. Initial stages of differentiation were similar across the juvenile CNS, whereas subsets of mature oligodendrocytes were enriched in specific regions in the adult brain. Newly formed oligodendrocytes were detected in the adult CNS and were responsive to complex motor learning. A second Pdgfra(+) population, distinct from OPCs, was found along vessels. Our study reveals the dynamics of oligodendrocyte differentiation and maturation, uncoupling them at a transcriptional level and highlighting oligodendrocyte heterogeneity in the CNS

NORSE and Super-Refractory Status Epilepticus: a Single-Center Retrospective Chart Review

Rationale: New-Onset Refractory Status Epilepticus (NORSE) is a rare life-threatening condition in previously healthy patients who develop new-onset medically-refractory status epilepticus of unclear etiology.1NORSE commonly leads to super-refractory status epilepticus (SRSE), a severe form of status epilepticus for which seizures persist despite 24 hours of adequate anti-seizure and anesthetic treatment. The goal of this study is to examine the clinical characteristics and epidemiology of super-refractory NORSE, a subset of SRSE, to determine risk and prognostic factors associated with this rare condition, and mortality rates. Methods: We performed a retrospective cohort study of all cases of SRSE admitted to Oregon Health & Science University, an academic tertiary care center between 2007 and 2016. Results: Among 358 patients monitored on continuous EEG for at least 4 days in a single admission, 67 (19%) were identified as having SRSE. In-hospital mortality for SRSE (all causes) was 30% (20), but for the specific NORSE group 15% (2), for pre-existing epilepsy 40% (4) and for symptomatic 32% (14). Conclusions: The results of this study are consistent with prior reports of NORSE epidemiology: the condition is rare, patients tend to be younger, female-predominate, and there have been no antibodies clearly-associated with the condition. A novel finding in this study was that 50% of NORSE cases had positive antibody testing– the majority of which were thyroid-associated antibodies (41.7%). Based on a population-based study at baseline of 5783 participants, 12.8% were positive for TPO antibodies with a higher prevalence in women compared to men.2 While thyroid-associated antibodies are thought to be non-specific markers of inflammation and/or autoimmunity, this supports the hypothesis that NORSE (or a subset of NORSE cases) may be autoimmune-mediated and establishes a potential autoimmune link

Puukomposiittialtaiden hakkeen täytön automatisoinnin suunnittelu

Opinnäytetyön tarkoituksena oli puukomposiittialtaiden hakkeen täytön automatisoinnin suunnittelu. Suunnittelu on tehty Woodiolle, joka sijaitsee Helsingissä. Työn tuloksena saatiin Woodio-yrityksen tarpeisiin soveltuva ja päivitetty automaatio- ja suunnitteluohje, Ohje saatiin rakennettua selkeästi ja niin, että tieto on helposti löydettävissä. Suunnittelussa on 3 vaihetta eli tärykuljetin, annostelukone ja muotin täyttöasema. Muotit täytetään hakkeella annostelukoneen avulla. Altaiden koon perusteella annostelukone annostelee oikean määrän haketta muottiin. Annostelunopeutta voidaan säätää muotin täyttymisen mukaan. Altaiden erilaiset muodot vaikuttavat muotin täyttymisen nopeuteen. Annostelukoneen lisäksi muotin täytössä käytetään apuna tärypöytää. Hakesäiliöstä hake kuljetetaan tärykuljettimella annostelijalle ja samalla hakkeesta poistetaan hienojakoinen pöly. Tässä opinnäytetyön suunnitelmassa yritettiin käyttää erilaisia koneita ja sovelluksia, joita on helppo käyttää , ja se soveltuu hyvin tähän käyttötarkoitukseen. Tässä suunnitelmassa on tarkoitus yhdistää erilaiset koneet ja laitteet toimimaan automaation avulla yhtenäisesti. Lisäksi muotin kuljettamiseen on suunniteltu Tiaportal V 16 -hihna, jolla muotti voitaisiin kuljettaa annostelukoneen alle

Strategies Towards the Hydrogenation of CO2 and Carboxylic Acid Derivatives

Increasing energy demands have been met with added combustion of fossil fuels. The massive quantities of carbon dioxide (CO2) given off as a byproduct of these processes have led to environmental and economical ramifications. Consequently, great emphasis has been placed in remediating CO2 emissions through Carbon Capture and Sequestration (CSS) technologies. A limitation of CSS is that it fails to productively use CO2. A complementary approach is to utilize CO2 as a C-1 source. This dissertation discusses several strategies for the valorization of CO2 to methanol (CH3OH) stemming from fundamental hydrogenation studies. Chapter 2 outlines a facile approach for the in situ generation of ester hydrogenation catalysts. Unlike traditional methods, this simple approach circumvents the use of sub-stoichiometric alkoxide base. Systematic studies of ligand and base effects on the hydrogenation of the esters, are disclosed. Generally, diphenylphosphinoethylamine, was found to form the most active catalyst for the hydrogenation of alkyl and aryl esters with >80% yield for select substrates. Mechanistic studies elucidated the unproductive, base-catalyzed decarbonylation of the formate ester with traditional alkoxide bases. Consequently, alternatives were investigated and K3PO4 was found to be a viable and compatible substitute. The improved insight from formate ester hydrogenation guided our studies for the one-pot hydrogenation of CO2 to CH3OH. Application of these catalysts and conditions to the cascade hydrogenation of CO2 identified incompatibility with Lewis acids. Chapter 3 focuses on this limitation and discloses a new class of ester hydrogenation catalysts that are compatible with Lewis acids. Application of these half-sandwich ester hydrogenation catalysts to the Lewis acidic cascade system led up to 8 turnovers of CH3OH in a single-pot batch reactor. Further studies implicate labile ligands as a source of inhibition. In Chapter 4, a conceptually novel approach is disclosed, wherein CO2 is captured using an amine scrubbing agent (NHMe2) and subsequently hydrogenated in a single pot to >500 turnovers of CH3OH. Up to 96% of CO2 was converted to a mixture of CH3OH and N,N-dimethylformamide (DMF). Mechanistic studies of the pathway identify DMF as a key intermediate. This strategy of carbon capture and hydrogenation provides a complementary approach to many industrial carbon capture methods. In an effort to develop an earth-abundant process for the hydrogenation of CO2 to CH3OH, iron catalysts were investigated as surrogates to the ruthenium catalysts used in Chapter 4. These iron-catalysts demonstrated high activity for the hydrogenation of amides yielding C–N bond scission products with high selectivity. DMF, a key intermediate in the CO2 to CH3OH pathway developed in Chapter 4, was hydrogenated to yield >1000 turnovers of CH3OH and HNMe2. Kinetic studies were performed to compare the activity of the earth abundant iron catalyst to ruthenium. Remarkably, under otherwise identical conditions, the iron and ruthenium catalysts displayed rates within a factor of 2. Application of these catalysts to the CO2-capture and hydrogenation pathway is also discussed. Finally, with the development of hydrogenation methodologies for C–N bond scission of formamides to yield CH3OH, complementary methods have been disclosed to yield the methylated amine through deoxy-hydrogenation. Fundamental studies were undertaken in Chapter 6 to explore the origin of selectivity for the hydrogenation of amides (C–N vs. C–O bond cleavage). Through these fundamental studies, a proton responsive catalyst was identified that enabled selective access to each product (C–N or C–O bond cleavage).PHDChemistryUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/140933/1/nomaanr_1.pd