Negative symptoms of schizophrenia and psychosocial treatment: thematic analysis of stakeholders’ perspectives

Objectives. Recent literature indicates variance in psychosocial treatment preferences for negative symptoms of schizophrenia. Attempts at defining therapeutic aims and outcomes for negative symptoms to date have not included major stakeholder groups. The aim of the present study was to address this gap through qualitative methods. Design. Thematic Analysis was applied to qualitative semi-structured interview data to gather the opinions of people who experience negative symptoms, carers, and healthcare professionals. Participants were recruited from two mental health sites (inpatient/community) to increase generalisability of results. Ten people participated in the research. Methods. Semi-structured interview scripts were designed utilising evidence from the review in Chapter 1 of effective psychosocial intervention components for specific negative symptoms. Interviews were audio recorded and transcribed verbatim. Thematic analysis was employed to analyse data. Results. A common theme across groups was the need for a personalised approach to intervention for negative symptoms. Other themes indicated different opinions in relation to treatment targets and the need for a sensitive and graded approach to all aspects of therapy. This approach needs to be supported across systemic levels of organisation with specific training needs for staff addressed. Conclusions. There is disparity in treatment preferences for negative symptoms across major stakeholders. The findings suggest an individualised approach to intervention of negative symptoms that is consistent with recovery. Implementation barriers and facilitators were identified and discussed. There remains a need to develop a better understanding of treatment preferences for patients.

The Shrine of ʿAbd al-Qādir al-Jīlānī in Baghdad & the Shrine of ʿAbd al-ʿAzīz al-Jīlānī in ʿAqra: Mapping the multiple orientations of two Qādirī Sufi shrines in Iraq

This thesis charts the stakeholder communities, physical environment and daily life of two little studied Qādiriyya Sufi shrines associated with Shaikh ʿAbd al-Qādir al-Jīlānī (1077 – 1165 AD), a 12th century Ḥanbalī Muslim theologian and the posthumous founder of one of the oldest Sufi orders in Islam. The first shrine is based in Baghdad and houses his burial chamber; and the second shrine, on the outskirts of the city of ‘Aqra in the Kurdish region of northern Iraq, is that of his son Shaikh ʿAbd al-ʿAzīz (died 1206 AD). The latter was also known for lecturing in Ḥanbalī theology in the region, and venerated for this as well as his association with Shaikh ʿAbd al-Qādir. Driven by the research question “What shapes the identity orientations of these two Qādiriyya Sufi shrines in modern times?” the findings presented here are the result of field research carried out between November 2009 and February 2014. This field research revealed a complex context in which the two shrines existed and interacted, influenced by both Sufi and non-Sufi stakeholders who identified with and accessed these shrines to satisfy a variety of spiritual and practical needs, which in turn influenced the way each considered and viewed the two shrines from a number of orientations. These overlapping orientations include the Qādirī Sufi entity and the resting place of its patron saint; the orthodox Sunnī mosque with its muftī-imams, who are employed by the Iraqi government; the local Shīʿa community’s neighbourhood saint’s shrine and its destination for spiritual and practical aid; and the local provider of welfare to the poor of the city (soup kitchen, funeral parlour and electricity-generation amongst other services). The research findings also revealed a continuously changing and adapting Qādirī Sufi scene not immune from the national and regional socio-religio-political environments in which the two shrines exist: a non-Sufi national political class vying to influence and manipulate these shrines for their own purposes; and powerful national sectarian factions jostling to do the same. The mixture of stakeholders using and associating with the two shrines were found to be influential shapers of these entities, both physically and spiritually. Through encountering and interacting with each other, most stakeholders contributed to maintaining and rejuvenating the two shrines, but some also sought to adapt and change them driven by their particular orientation’s perspective.

Convergent evolution of PICIs-mediated phage interference

Staphylococcal pathogenicity islands (SaPIs), the prototype members of the family of phage inducible chromosomal islands (PICIs), are extremely mobile phage satellites, which are transferred between bacterial hosts after their induction by a helper phage. The intimate relationship between SaPIs and their helper phages is one of the most studied examples of virus satellite interactions in prokaryotic cells. SaPIs encode and disseminate virulence and fitness factors, representing a driving force for bacterial adaptation and pathogenesis. Many SaPIs encode a conserved morphogenetic operon, including a core set of genes whose function allows them to parasitize and exploit the phage life cycle. One of the central mechanisms of this molecular piracy is the specific packaging of the SaPI genomes into reduced sized capsid structures derived from phage proteins. Pac phages were classically thought to be the only phages involved in the mobilisation of phage-mediated virulence genes, including the transfer of SaPIs within related and non-related bacteria. This study presents the involvement of S. aureus cos phages in the intra- and intergeneric transfer of cos SaPIs for the first time. A novel example of molecular parasitism is shown, by which this newly characterised group of cos SaPIs uses two distinct and complementary mechanisms to take over the helper phage packaging machinery for their own reproduction. SaPIbov5, the prototype of the cos SaPIs, does not encode the characteristic morphogenetic operon found in pac SaPIs. However, cos SaPIs features both pac and cos phage cleavage sequences in their genome, ensuring SaPI packaging in small- and full-sized phage particles, depending on the helper phage. Moreover, cos-site packaging in S. aureus was shown to require the activity of a phage HNH nuclease. The HNH protein functions together with the large terminase subunit, triggering cleavage and melting of the cos-site sequence. In addition, a novel piracy strategy, severely interfering with the helper phage reproduction, was identified in cos SaPIs and characterised. This mechanism of piracy depends on the cos SaPI-encoded ccm gene, which encodes a capsid protein involved in the formation of small phage particles, modifying the assembling process via a scaffolding mechanism. This strategy resembles the ones described for pac SaPIs and represents a remarkable example of convergent evolution. A further convergent mechanism of capsid size-reduction was identified and characterised for the Enterococcus faecalis EfCIV583 pathogenicity island, another member of the PICI family. In this case, the self-encoded CpmE conducts this molecular piracy through a putative scaffolding function. Similar to cos SaPIs, EfCIV583 carries the helper phage cleavage sequence in its genome enabling its mobilisation by the phage terminase complex. The results presented in this thesis show how two examples of non-related members of the PICI family follow the same evolutionary convergent strategy to interfere with their helper phage. These findings could indicate that the described strategies might be widespread among PICIs and implicate a significant impact of PICIs mediated-virulence gene transfer in bacterial evolution and the emergence of pathogenic bacteria.