"It's just not cricket". Or is it?

Considers the Wolverhampton County Court decision in Bartlett v English Cricket Board Association of Cricket Officials on whether cricket umpires at an amateur match were liable for injuries to a player based on their inspection of the condition of the cricket ground after heavy rain and their decision to allow play to proceed. Comments on the approach to the umpires' standard of care.

Non-pharmacological interventions for cognitive impairment due to systemic cancer treatment (Review)

Background

It is estimated that up to 75% of cancer survivors may experience cognitive impairment as a result of cancer treatment and given the increasing size of the cancer survivor population, the number of affected people is set to rise considerably in coming years. There is a need, therefore, to identify effective, non-pharmacological interventions for maintaining cognitive function or ameliorating cognitive impairment among people with a previous cancer diagnosis.
Objectives

To evaluate the cognitive effects, non-cognitive effects, duration and safety of non-pharmacological interventions among cancer patients targeted at maintaining cognitive function or ameliorating cognitive impairment as a result of cancer or receipt of systemic cancer treatment (i.e. chemotherapy or hormonal therapies in isolation or combination with other treatments).
Search methods

We searched the Cochrane Centre Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PUBMED, Cumulative Index of Nursing and Allied Health Literature (CINAHL) and PsycINFO databases. We also searched registries of ongoing trials and grey literature including theses, dissertations and conference proceedings. Searches were conducted for articles published from 1980 to 29 September 2015.
Selection criteria

Randomised controlled trials (RCTs) of non-pharmacological interventions to improve cognitive impairment or to maintain cognitive functioning among survivors of adult-onset cancers who have completed systemic cancer therapy (in isolation or combination with other treatments) were eligible. Studies among individuals continuing to receive hormonal therapy were included. We excluded interventions targeted at cancer survivors with central nervous system (CNS) tumours or metastases, non-melanoma skin cancer or those who had received cranial radiation or, were from nursing or care home settings. Language restrictions were not applied.
Data collection and analysis

Author pairs independently screened, selected, extracted data and rated the risk of bias of studies. We were unable to conduct planned meta-analyses due to heterogeneity in the type of interventions and outcomes, with the exception of compensatory strategy training interventions for which we pooled data for mental and physical well-being outcomes. We report a narrative synthesis of intervention effectiveness for other outcomes.
Main results

Five RCTs describing six interventions (comprising a total of 235 participants) met the eligibility criteria for the review. Two trials of computer-assisted cognitive training interventions (n = 100), two of compensatory strategy training interventions (n = 95), one of meditation (n = 47) and one of physical activity intervention (n = 19) were identified. Each study focused on breast cancer survivors. All five studies were rated as having a high risk of bias. Data for our primary outcome of interest, cognitive function were not amenable to being pooled statistically. Cognitive training demonstrated beneficial effects on objectively assessed cognitive function (including processing speed, executive functions, cognitive flexibility, language, delayed- and immediate- memory), subjectively reported cognitive function and mental well-being. Compensatory strategy training demonstrated improvements on objectively assessed delayed-, immediate- and verbal-memory, self-reported cognitive function and spiritual quality of life (QoL). The meta-analyses of two RCTs (95 participants) did not show a beneficial effect from compensatory strategy training on physical well-being immediately (standardised mean difference (SMD) 0.12, 95% confidence interval (CI) -0.59 to 0.83; I2= 67%) or two months post-intervention (SMD - 0.21, 95% CI -0.89 to 0.47; I2 = 63%) or on mental well-being two months post-intervention (SMD -0.38, 95% CI -1.10 to 0.34; I2 = 67%). Lower mental well-being immediately post-intervention appeared to be observed in patients who received compensatory strategy training compared to wait-list controls (SMD -0.57, 95% CI -0.98 to -0.16; I2 = 0%). We assessed the assembled studies using GRADE for physical and mental health outcomes and this evidence was rated to be low quality and, therefore findings should be interpreted with caution. Evidence for physical activity and meditation interventions on cognitive outcomes is unclear.
Authors' conclusions

Overall, the, albeit low-quality evidence may be interpreted to suggest that non-pharmacological interventions may have the potential to reduce the risk of, or ameliorate, cognitive impairment following systemic cancer treatment. Larger, multi-site studies including an appropriate, active attentional control group, as well as consideration of functional outcomes (e.g. activities of daily living) are required in order to come to firmer conclusions about the benefits or otherwise of this intervention approach. There is also a need to conduct research into cognitive impairment among cancer patient groups other than women with breast cancer.

Violência contra a mulher: estudo das ocorrências registradas na Delegacia Especializada de atendimento às mulheres – Rio Grande-RS

Introdução: no Brasil, a violência contra a mulher foi reconhecida somente com a Convenção Belém do Pará, em 1995. A partir daí, inúmeras medidas para prevenção e combate foram instituídas, entre elas a criação das Delegacias Especializadas de Atendimento às Mulheres (DEAM) e a Lei Maria da Penha. No entanto, muitas mulheres ainda são vitimadas, na maioria das vezes dentro do próprio lar. Objetivos: delinear o perfil das mulheres vítimas de violência; identificar as formas de violência registradas na DEAM da cidade do Rio Grande/RS; identificar os motivos que levam à prática da violência e descrever os atos violentos perpetrados, por parceiro íntimo, às mulheres que registraram ocorrência na DEAM. Metodologia: estudo documental, quanti e qualitativo, de natureza exploratória, descritiva e delineamento transversal. Fizeram parte do estudo todas as ocorrências cujas vítimas eram mulheres com 18 anos ou mais. O espaço temporal adotado estendeu-se de agosto de 2009, quando foi implantada a delegacia, a dezembro de 2011. Os dados foram coletados entre outubro de 2011 e março de 2012. Para a coleta, foi elaborado e aprovado, após testagem, um instrumento contendo informações acerca do agressor, da vítima, bem como do tipo de violência praticada. Os dados foram digitados em planilhas do tipo Excel. A análise quantitativa foi efetuada por meio de estatística descritiva e do software estatístico SPSS versão 17.0. Para o estudo qualitativo utilizou-se a análise de conteúdo. Esse projeto foi aprovado pelo Comitê de Ética em Pesquisa na Área da Saúde, da Universidade Federal do Rio Grande sob Parecer no 137/2011. Resultados: estão descritos em dois artigos. Analisaram-se 902 ocorrências policiais evidenciando-se que a maioria das vitimas eram mulheres brancas, jovens, com baixa escolaridade. Ainda foi possível identificar que o Centro da cidade ocupou a segunda posição como local de moradia das vítimas, desmitificando a idéia de que a violência predomina na periferia. A violência física prevaleceu nos registros notificados, seguida do descumprimento de ordem judicial. Além disso, encontrou-se a reincidência de denúncias, o que pode estar atrelado à morosidade judicial. Observou-se também, que existem diversos motivos desencadeadores da violência, no entanto todos eles apresentam como pano de fundo as questões associadas ao gênero. A simultaneidade da violência bem como a extensão aos filhos, família e sociedade retratam a gravidade do fenômeno e a necessidade de se rever a resolutividade das medidas protetivas e das penas atribuídas aos agressores. Conclusões: este estudo expôs, parcialmente, a situação da violência contra a mulher no município, pois se sabe que existem muitos casos velados que não chegam a ser notificados. Entretanto, evidenciou-se o predomínio da violência física cometida por parceiro íntimo repercutindo em graves consequências à vida das vítimas. Assim, julga-se ímpar a implementação de uma rede efetiva de apoio a essas mulheres bem como a atuação de equipe multidisciplinar capacitada, coesa e sensível ao problema, incluindo os profissionais da saúde, que precisam, ainda, estar ciente da obrigatoriedade da notificação compulsória, fundamental para a formulação de novas políticas públicas de combate e prevenção a esse fenômeno.

The Corporate Manslaughter and Corporate Homicide Act 2007 or the Health and Safety (Offences) Act 2008: corporate killing and the law

This thesis examines the regulatory and legislative approach taken in the United Kingdom to deal with deaths arising from work related activities and, in particular, deaths that can be directly attributed to the behaviour of corporations and other organisations. Workplace health and safety has traditionally been seen in the United Kingdom as a regulatory function which can be traced to the very earliest days of the Industrial Revolution. With an emphasis on preventing workplace accidents and ill-health through guidance, advice and support, the health and safety legislation and enforcement regime which had evolved over the best part of two centuries was considered inadequate to effectively punish corporations considered responsible for deaths caused by their activities following a series of disasters in the late twentieth and early twenty-first centuries. To address this apparent inadequacy, the Corporate Manslaughter and Corporate Homicide Act 2007 was introduced creating the offence of corporate manslaughter and corporate homicide. Based on a gross breach of a relevant duty of care resulting in the death of a person, the Act effectively changed what had previously considered a matter of regulation, an approach that had obvious weaknesses and shortcomings, to one of crime and criminal law. Whether this is the best approach to dealing with deaths caused by an organisation is challenged in this thesis and the apparent distinction between ‘criminal’ and ‘regulatory’ offences is also examined. It was found that an amended Health and Safety at Work etc. Act 1974 to include a specific offence of corporate killing, in conjunction with the Health and Safety (Offences) Act 2008 would almost certainly have resulted in a more effective approach to dealing with organisations responsible for causing deaths as consequence of their activities. It was also found that there was no substantive difference between ‘regulatory’ and ‘criminal’ law other than the stigma associated with the latter, and that distinction would almost certainly disappear, at least in the context of worker safety, as a consequence of the penalties available following the introduction of the Health and Safety (Offences) Act 2008.

Ordenanzas espedidas por la Lejislatura Provincial de Túquerres en sesiones estraordinarias del mes de enero de 1854 y ordinarias del mismo año

25 p.

L'intervention de l'État pour protéger les enfants contre l'obésité infantile : quelles mesures possibles?

Le présent essai s’intéresse aux mesures de protection offertes par la législation québécoise en matière de droit de l’enfant, à travers le Code civil du Québec et la Loi sur la protection de la jeunesse. Ces mesures seront analysées pour évaluer leur applicabilité et leur pertinence à l’égard de la problématique de l’obésité infantile, un problème de santé publique de plus en plus préoccupant au Québec comme ailleurs dans le monde. L’étude révèle que le fait de fournir des aliments malsains à son enfant et de lui transmettre de mauvaises habitudes de vie sont des gestes qui pourraient théoriquement être considérés comme des manquements aux devoirs d’entretien et d’éducation, attributs de l’autorité parentale. Ces gestes peuvent également être perçus comme de la négligence sur le plan physique et sur le plan de la santé. Dans ces cas, certaines mesures sont applicables selon la situation.

Le processus de thermo-érosion du pergélisol dans la zone de pergélisol continu

Les polygones à coin de glace sont très répandus dans la zone du pergélisol continu. Lorsque le ruissellement d’eau de fonte nivale s’infiltre de façon concentrée dans une cavité, il peut initier le processus de thermo-érosion du pergélisol (notamment des coins de glace) pouvant mener à la formation de ravins. Dans la vallée de Qalikturvik sur l’Ile Bylot (NU, Canada), le développement de ravins de thermo-érosion dans un milieu de polygones à coins de glace entraîne comme impact : i. la réorganisation des réseaux de drainage impliquant un assèchement des milieux humides en marge des chenaux d’érosion, ii. des variations dans le régime thermique et de l’humidité de proche-surface et iii. la prise en charge et le déplacement des sédiments vers l’extérieur du bassin-versant. L’objectif de cette thèse vise à approfondir les connaissances géomorphologiques propres au ravinement par thermo-érosion, d’examiner, caractériser et quantifier les impacts du ravinement (tel que sus-mentionné en i. ii. iii.) et le rôle de celui-ci dans une optique d’évolution du paysage périglaciaire à l’échelle temporelle de l’année à la décennie. Les ravins sont dynamiques : un ravin en particulier déclenché en 1999 et étudié depuis s’érodait à une vitesse de 38 à 50 m/a durant sa première décennie d’existence, pour atteindre une longueur totale de ~750 m et une surface érodée de ~25 000 m² en 2009. Des puits sont localisés près des zones de ravinement actives ; des levées alluviale, mares et polygones effondrés dans les zones stabilisées post-perturbation. Sur la terrasse de polygones recouvrant le plancher de la vallée au site à l’étude, 35 ravins furent identifiés et 1401 polygones furent perturbés avec 200 000 m³ de sols transportés. Une amélioration du drainage, une dégradation de la capacité de rétention de l’humidité, une transition d’un écoulement de ruissellement vers un écoulement canalisé caractérise les aires ravinées et leurs environs. Les polygones intacts sont homogènes d’un à l’autre et dans leurs centres ; les polygones perturbés ont une réponse hétérogène (flore, humidité et régime thermique). Les milieux érodés hétérogènes succèdent aux milieux homogènes et deviennent le nouvel état d’équilibre pour plusieurs décennies.

Ograniczona względami ekonomicznymi dostępność świadczeń zdrowotnych a naruszenie przez lekarza reguł ostrożności

Odpowiedzialność karną lekarza łączy się powszechnie z problematyką błędu medycznego, choć właściwie odpowiada on nie za sam błąd medyczny, jako że prawo karne nie zna przestępstwa polegającego na popełnieniu błędu medycznego, ale za ewentualne jego skutki, które mogą być kwalifikowane jako nieumyślne spowodowanie śmierci, nieumyślne spowodowanie ciężkiego, średniego albo lekkiego uszczerbku na zdrowiu bądź nieumyślne narażenie na niebezpieczeństwo utraty życia albo ciężkiego uszczerbku na zdrowiu. Nie można oczywiście wykluczyć wystąpienia sytuacji, w której lekarz swoim zachowaniem zrealizowałby znamiona typu umyślnego, jednakże na potrzeby niniejszej publikacji przyjęto, że co do zasady lekarz działa w celu ratowania dóbr prawnych, jakimi są życie i zdrowie pacjenta, nie zaś z zamiarem narażenia ich na niebezpieczeństwo bądź naruszenia, a ewentualne negatywne skutki dla życia i pacjenta, powstałe w miejsce lub obok zamierzonego stanu rzeczy, nie są przez niego objęte umyślnością. Kluczowym warunkiem uznania, że czyn popełniony został nieumyślnie jest ustalenie, że sprawca naruszył reguły ostrożnego postępowania, wymagane w danych okolicznościach. W odniesieniu do zawodu lekarza na pierwszy plan wysuwa się wśród nich wymóg stosowania się do wskazań aktualnej wiedzy medycznej. Autorka przekłada ten obowiązek na grunt realiów systemu ochrony zdrowia i rozważa, jaki wpływ na jego niedopełnienie mają okoliczności ograniczonej względami ekonomicznymi dostępności świadczeń zdrowotnych oraz w jaki sposób niedostatek środków finansowych może rzutować na naruszenie przez lekarza reguł ostrożnego postępowania, o których mowa w art. 9 § 2 Kodeksu karnego.

Dopuszczalność i skutki potwierdzenia czynności dokonanej bez wymaganej przez umowę lub statut zgody organu spółki

W artykule autorzy podejmują się dokonania analizy zagadnienia dotyczącego możliwości naruszenia umowy spółki lub statutu przez członków zarządu oraz wpływu takiego naruszenia na ważność podjętej czynności prawnej. Zagadnienie to wywołuje liczne problemy praktyczne, chociażby z uwagi na obowiązek każdorazowej weryfikacji przed zawarciem umowy listy czynności, na dokonanie których statut lub umowa spółki zastrzega sobie taki wymóg. Nie ma tu znaczenia dobra czy zła wiara kontrahenta, który ma świadomość o istnieniu takiego zapisu dla ważności danej czynności prawnej. Zgoła odmienna jest sytuacja członka zarządu, dla którego uzyskanie takiej zgody jest ważne, z uwagi na naruszenia umowy spółki albo statutu, a w konsekwencji jego odpowiedzialność odszkodowawczą do dochodzenia ewentualnego odszkodowania za szkodę wyrządzoną działaniem lub zaniechaniem. Pamiętać jednak należy, że do istnienia odpowiedzialności niezbędne jest wykazanie szkody. Jednakże biorąc pod uwagę uwarunkowania biznesowe niekiedy trudno uzyskać zgodę rady nadzorczej lub walnego zgromadzenia wspólników na taką zgodę. Powstaje wtedy pytanie, czy można ją uzyskać następczo. Autorzy w artykule dokonują analizy stawiając tezę, iż możliwe jest następcze wyrażenie zgody na dokonaną bez uprzedniej zgody czynność prawną. Dokonując wnioskowania a maiori ad minus można w ocenie autorów dopuścić potwierdzenie takiej czynności następczo i to nie tylko w wymaganym dwumiesięcznym terminie, ale nawet późniejszym, co może mieć wpływ na ich ewentualne wyłączenie odpowiedzialności z tytułu naruszenia postanowień umowy spółki (statutu). Całość rozważań ściśle oscyluje wokół praktycznych problemów pojawiających się funkcjonowaniu spółki.

Proyecto de investigación la construcción irregular acercamiento a sus causas y efectos. Análisis en un determinado sector de la ciudad de Cuenca

El análisis de las construcciones irregulares en la ciudad de Cuenca es importante para entender el fenómeno entre lo que la norma urbanística permite en el ámbito de la construcción y la necesidad del propietario. Es necesario considerar dos panoramas: los asentamientos informales en zonas no permitidas, situación que no se ha visibilizado aún en gran magnitud; y las edificaciones que se han modificado incumpliendo las normas urbanísticas. Se analizarán construcciones en las que se establece que entre las posibles razones para su modificación están la necesidad de mejorar la funcionalidad de la misma o generar desarrollo económico familiar, originando probablemente afectaciones al paisaje urbano e inclusive el deterioro de la calidad de vida de los vecinos. El proyecto de investigación consiste en localizar las edificaciones en el área de actuación que infringen las ordenanzas vigentes en el Cantón Cuenca, con la finalidad de generar soluciones en busca de la homogeneidad del sector.

A gravitação da ética do cuidado na mediação : intervenção social e escolar nas escolas

Na resolução de conflitos, no incumprimento de normas e nas situações de indisciplina escolar, exigem-se mediadores e programas de mediação. Na implementação destes programas é essencial formar mediadores para intervirem em contexto socioeducativo com alunos, professores e família, sendo exigido a esses profissionais uma ética profissional mediadora. A necessidade de educar os alunos para integrarem as equipes de mediação implica a promoção de valores de convivência e uma ética do cuidado com os outros. A ética do cuidado e do encontro permite mais possibilidades de convívio e novas formas de existência humana. Procuramos interpretar os pontos de vista de alguns autores sobre a mediação (modelos e programas), destacando a educação para a tolerância, solidariedade, responsabilidade e cidadania, que são exigências da escola no âmbito da educação para os valores. A mediação contribui para resolver conflitos, melhorar a comunicação, as relações e a convivência.

Adhesives for fixed orthodontic bands

Background: Orthodontic treatment involves using fixed or removable appliances (dental braces) to correct the positions of teeth. It has been shown that the quality of treatment result obtained with fixed appliances is much better than with removable appliances. Fixed appliances are, therefore, favoured by most orthodontists for treatment. The success of a fixed orthodontic appliance depends on the metal attachments (brackets and bands) being attached securely to the teeth so that they do not become loose during treatment. Brackets are usually attached to the front and side teeth, whereas bands (metal rings that go round the teeth) are more commonly used on the back teeth (molars). A number of adhesives are available to attach bands to teeth and it is important to understand which group of adhesives bond most reliably, as well as reducing or preventing dental decay during the treatment period. :Objectives: To evaluate the effectiveness of the adhesives used to attach bands to teeth during fixed appliance treatment, in terms of: (1) how often the bands come off during treatment; and (2) whether they protect the banded teeth against decay during fixed appliance treatment. Search methods: The following electronic databases were searched: Cochrane Oral Health's Trials Register (searched 2 June 2016), Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 5) in the Cochrane Library (searched 2 June 2016), MEDLINE Ovid (1946 to 2 June 2016) and EMBASE Ovid (1980 to 2 June 2016). We searched ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform for ongoing trials. No restrictions were placed on the language or date of publication when searching the electronic databases. Selection criteria: Randomised and controlled clinical trials (RCTs and CCTs) (including split-mouth studies) of adhesives used to attach orthodontic bands to molar teeth were selected. Patients with full arch fixed orthodontic appliance(s) who had bands attached to molars were included. Data collection and analysis: All review authors were involved in study selection, validity assessment and data extraction without blinding to the authors, adhesives used or results obtained. All disagreements were resolved by discussion. Main results: Five RCTs and three CCTs were identified as meeting the review's inclusion criteria. All the included trials were of split-mouth design. Four trials compared chemically cured zinc phosphate and chemically cured glass ionomer; three trials compared chemically cured glass ionomer cement with light cured compomer; one trial compared chemically cured glass ionomer with a chemically cured glass phosphonate. Data analysis was often inappropriate within the studies meeting the inclusion criteria. Authors' conclusions: There is insufficient high quality evidence with regard to the most effective adhesive for attaching orthodontic bands to molar teeth. Further RCTs are required.

Target acquired: Progress and promise of targeted therapeutics in the treatment of prostate cancer

Cancer is fundamentally a genomic disease caused by mutations or rearrangements in the DNA or epigenetic machinery of a patient. An emerging field in cancer treatment targets key aberrations arising from the mutational landscape of an individual patient’s disease rather than employing a cancer-wide cytotoxic therapy approach. In prostate cancer in particular, where there is an observed variation in response to standard treatments between patients with disease of a similar pathological stage and grade, mutationdirected treatment may grow to be a viable tool for clinicians to tailor more effective treatments. This review will describe a number of mutations across multiple forms of cancer that have been successfully antagonised by targeted therapeutics including their identification, the development of targeted compounds to combat them and the development of resistance to these therapies. This review will continue to examine these same mutations in the treatment and management of prostate cancer; the prevalence of targetable mutations in prostate cancer, recent clinical trials of targeted-agents and the potential or limitations for their use.

Preventing vasospasm improves outcome after aneurysmal subarachnoid hemorrhage: rationale and design of CONSCIOUS-2 and CONSCIOUS-3 trials

Cerebral vasospasm after aneurysmal subarachnoid hemorrhage (aSAH) is a frequent but unpredictable complication associated with poor outcome. Current vasospasm therapies are suboptimal; new therapies are needed. Clazosentan, an endothelin receptor antagonist, has shown promise in phase 2 studies, and two randomized, double-blind, placebo-controlled phase 3 trials (CONSCIOUS-2 and CONSCIOUS-3) are underway to further investigate its impact on vasospasm-related outcome after aSAH. Here, we describe the design of these studies, which was challenging with respect to defining endpoints and standardizing endpoint interpretation and patient care. Main inclusion criteria are: age 18-75 years; SAH due to ruptured saccular aneurysm secured by surgical clipping (CONSCIOUS-2) or endovascular coiling (CONSCIOUS-3); substantial subarachnoid clot; and World Federation of Neurosurgical Societies grades I-IV prior to aneurysm-securing procedure. In CONSCIOUS-2, patients are randomized 2:1 to clazosentan (5 mg/h) or placebo. In CONSCIOUS-3, patients are randomized 1:1:1 to clazosentan 5, 15 mg/h, or placebo. Treatment is initiated within 56 h of aSAH and continued until 14 days after aSAH. Primary endpoint is a composite of mortality and vasospasm-related morbidity within 6 weeks of aSAH (all-cause mortality, vasospasm-related new cerebral infarction, vasospasm-related delayed ischemic neurological deficit, neurological signs or symptoms in the presence of angiographic vasospasm leading to rescue therapy initiation). Main secondary endpoint is extended Glasgow Outcome Scale at week 12. A critical events committee assesses all data centrally to ensure consistency in interpretation, and patient management guidelines are used to standardize care. Results are expected at the end of 2010 and 2011 for CONSCIOUS-2 and CONSCIOUS-3, respectively.

Antibody-Drug Conjugates for Tumor Targeting-Novel Conjugation Chemistries and the Promise of non-IgG Binding Proteins

Antibody-drug conjugates (ADCs) have emerged as a promising class of anticancer agents, combining the specificity of antibodies for tumor targeting and the destructive potential of highly potent drugs as payload. An essential component of these immunoconjugates is a bifunctional linker capable of reacting with the antibody and the payload to assemble a functional entity. Linker design is fundamental, as it must provide high stability in the circulation to prevent premature drug release, but be capable of releasing the active drug inside the target cell upon receptor-mediated endocytosis. Although ADCs have demonstrated an increased therapeutic window, compared to conventional chemotherapy in recent clinical trials, therapeutic success rates are still far from optimal. To explore other regimes of half-life variation and drug conjugation stoichiometries, it is necessary to investigate additional binding proteins which offer access to a wide range of formats, all with molecularly defined drug conjugation. Here, we delineate recent progress with site-specific and biorthogonal conjugation chemistries, and discuss alternative, biophysically more stable protein scaffolds like Designed Ankyrin Repeat Proteins (DARPins), which may provide such additional engineering opportunities for drug conjugates with improved pharmacological performance.